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Sample records for vascular function inflammation

  1. Microvesicles Derived from Inflammation-Challenged Endothelial Cells Modulate Vascular Smooth Muscle Cell Functions.

    Science.gov (United States)

    Pan, Qunwen; Liu, Hua; Zheng, Chunyan; Zhao, Yuhui; Liao, Xiaorong; Wang, Yan; Chen, Yanfang; Zhao, Bin; Lazartigues, Eric; Yang, Yi; Ma, Xiaotang

    2016-01-01

    Purpose: Microvesicles (MV) can modulate the function of recipient cells by transferring their contents. Our previous study highlighted that MV released from tumor necrosis factor-α (TNF-α) plus serum deprivation (SD)-stimulated endothelial progenitor cells, induce detrimental effects on endothelial cells. In this study, we investigated the potential effects of endothelial MV (EMV) on proliferation, migration, and apoptosis of human brain vascular smooth cells (HBVSMC). Methods: EMV were prepared from human brain microvascular endothelial cells (HBMEC) cultured in a TNF-α plus SD medium. RNase-EMV were made by treating EMV with RNase A for RNA depletion. The proliferation, apoptosis and migration abilities of HBVSMC were determined after co-culture with EMV or RNase-EMV. The Mek1/2 inhibitor, PD0325901, was used for pathway analysis. Western blot was used for analyzing the proteins of Mek1/2, Erk1/2, phosphorylation Erk1/2, activated caspase-3 and Bcl-2. The level of miR-146a-5p was measured by qRT-PCR. Results: (1) EMV significantly promoted the proliferation and migration of HBVSMC. The effects were accompanied by an increase in Mek1/2 and p-Erk1/2, which could be abolished by PD0325901; (2) EMV decreased the apoptotic rate of HBVSMC by approximately 35%, which was accompanied by cleaved caspase-3 down-regulation and Bcl-2 up-regulation; (3) EMV increased miR-146a-5p level in HBVSMC by about 2-folds; (4) RNase-treated EMV were less effective than EMV on HBVSMC activities and miR-146a-5p expression. Conclusion: EMV generated under inflammation challenge can modulate HBVSMC function and fate via their carried RNA. This is associated with activation of theMek1/2/Erk1/2 pathway and caspase-3/Bcl-2 regulation, during which miR-146a-5p may play an important role. The data suggest that EMV derived from inflammation-challenged endothelial cells are detrimental to HBVSMC homeostatic functions, highlighting potential novel therapeutic targets for vascular diseases.

  2. Effects of acute exposure to moderate altitude on vascular function, metabolism and systemic inflammation.

    Directory of Open Access Journals (Sweden)

    Anne-Christin Stöwhas

    Full Text Available Travel to mountain areas is popular. However, the effects of acute exposure to moderate altitude on the cardiovascular system and metabolism are largely unknown.To investigate the effects of acute exposure to moderate altitude on vascular function, metabolism and systemic inflammation.In 51 healthy male subjects with a mean (SD age of 26.9 (9.3 years, oxygen saturation, blood pressure, heart rate, arterial stiffness, lipid profiles, low density lipoprotein (LDL particle size, insulin resistance (HOMA-index, highly-sensitive C-reactive protein and pro-inflammatory cytokines were measured at 490 m (Zurich and during two days at 2590 m, (Davos Jakobshorn, Switzerland in randomized order. The largest differences in outcomes between the two altitudes are reported.Mean (SD oxygen saturation was significantly lower at 2590 m, 91.0 (2.0%, compared to 490 m, 96.0 (1.0%, p<0.001. Mean blood pressure (mean difference +4.8 mmHg, p<0.001 and heart rate (mean difference +3.3 bpm, p<0.001 were significantly higher at 2590 m, compared to 490 m, but this was not associated with increased arterial stiffness. At 2590 m, lipid profiles improved (median difference triglycerides -0.14 mmol/l, p=0.012, HDL +0.08 mmol/l, p<0.001, total cholesterol/HDL-ratio -0.25, p=0.001, LDL particle size increased (median difference +0.45 nm, p=0.048 and hsCRP decreased (median difference -0.18 mg/l, p=0.024 compared to 490 m. No significant change in pro-inflammatory cytokines or insulin resistance was observed upon ascent to 2590 m.Short-term stay at moderate altitude is associated with increased blood pressure and heart rate likely due to augmented sympathetic activity. Exposure to moderate altitude improves the lipid profile and systemic inflammation, but seems to have no significant effect on glucose metabolism.ClinicalTrials.gov NCT01130948.

  3. Acute effects of different types of oil consumption on endothelial function, oxidative stress status and vascular inflammation in healthy volunteers.

    Science.gov (United States)

    Tousoulis, Dimitris; Papageorgiou, Nikolaos; Antoniades, Charalambos; Giolis, Anastasios; Bouras, George; Gounari, Panagiota; Stefanadi, Elli; Miliou, Antigoni; Psaltopoulou, Theodora; Stefanadis, Christodoulos

    2010-01-01

    Consumption of different types of oil may have different effects on cardiovascular risk. The exact role of maize oil, cod liver oil, soya oil and extra virgin olive oil on endothelial function, oxidative stress and inflammation is unknown. We evaluated the effect of acute consumption of these types of oil on endothelial function, oxidative stress and inflammation in healthy adults. Thirty-seven healthy volunteers were randomised to receive an oral amount of each type of oil or water. Endothelial function was evaluated by gauge-strain plethysmography at baseline and 1, 2 and 3 h after consumption. Oxidative stress status was determined by total lipid peroxides (PEROX), while inflammatory process was estimated by measuring the soluble form of vascular adhesion molecule 1. Serum levels of the two previous markers were measured at baseline and 3 h after oil consumption. Reactive hyperaemia (RH) was significantly decreased after maize oil consumption compared with controls (P consumption of cod liver oil and soya oil induced a significant improvement of RH after 1 h, compared with controls (P consumption on endothelium-independent dilatation, total lipid PEROX and vascular adhesion molecule 1 serum levels. Consumption of maize oil leads to impaired endothelial function, while soya oil and cod liver oil slightly improve endothelial function. However, all types of oils did not affect inflammatory process and systemic oxidative stress, suggesting that their effect on endothelial function may not be mediated by free radicals bioavailability.

  4. Is there any association of personality traits with vascular endothelial function or systemic inflammation?

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    Reza Bagherian Sararoudi

    2014-01-01

    Full Text Available Background: Evidences showed association of some personality traits with increased risk of cardiovascular diseases, but mediated mechanisms are not entirely described. In this study, we investigated the association of different personality traits with systemic inflammation and endothelial function as probable mediators. Methods: This cross-sectional study was conducted in 2011 on 40-60 years old employees of an industrial company located in Isfahan city (central Iran. Participants were selected through simple random sampling. Personality types were evaluated using the neuroticism-extroversion-openness personality inventory and systemic inflammatory status was determined with high sensitive C-reactive protein (hs-CRP level. To evaluate endothelial function flow mediated dilation (FMD were measured. The obtained data were analyzed with univariate correlation and multiple linear regression tests. Results: A total of 254 cases with mean age of 51.4 ± 6.1 years were evaluated. There was no significant relationship between hs-CRP level and FMD with the personality traits in univariate analysis. In multivariate analysis, no association was found between the scores of personality traits and FMD with controlling the factors such as age, body mass index dyslipidemia, hypertension and diabetes. Only there was an inverse association between conscientiousness score and hs-CRP (β = −0.241, P = 0.013. Conclusions: In our population who were the employees of an industrial company, no relationship was found between specific personality trait and endothelial dysfunction. However, we found that the personality trait of responsibility (conscientiousness is negatively associated with inflammation. Further multi-center studies and also cohort studies are recommended in this regard.

  5. Is there any association of anxiety-depressive symptoms with vascular endothelial function or systemic inflammation?

    Directory of Open Access Journals (Sweden)

    Gholam Reza Kheirabadi

    2013-01-01

    Full Text Available Background: Studies have shown the association of mood disorders and endothelial dysfunction, and increased risk of cardiovascular disease; however, mediatory mechanisms are not entirely clarified in this regard. We investigated the relationship between depression/anxiety symptoms with systemic inflammation and endothelial function. Materials and Methods: This cross-sectional study was performed in 2011 on employees of an oil company located in the Isfahan city (central Iran. Participants were selected with clustered random sampling. Anxiety and depression were evaluated by Hospital Anxiety Depression Scale (HADS. Systemic inflammatory status was evaluated by measuring sensitive C-reactive protein (high sensitive-CRP. To evaluate the endothelial function flow-mediated dilation (FMD was measured. Results: During the study period, 254 participants (mean age = 51.4 ΁ 6.1 years were evaluated. No significant relationship was found between high sensitive-CRP or FMD and any of the variables of anxiety or depression. In multivariate analysis, by controlling the possible confounding factors, no association was found between anxiety score, depression, or the overall score of HADS with high sensitive-CRP or FMD. After the separate analysis of patients with and without diabetes, depression score was correlated inversely with FMD among patients with diabetes (r = 0.525, P = 0.021. Conclusion: According to the results, in the studied population, there was no relationship between anxiety/depression with systemic inflammation or endothelial dysfunction, while in individuals with diabetes, depression was associated with endothelial dysfunction. In this regard more cohort studies are recommended.

  6. Oxidative stress and vascular inflammation in aging.

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    El Assar, Mariam; Angulo, Javier; Rodríguez-Mañas, Leocadio

    2013-12-01

    Vascular aging, a determinant factor for cardiovascular disease and health status in the elderly, is now viewed as a modifiable risk factor. Impaired endothelial vasodilation is a early hallmark of arterial aging that precedes the clinical manifestations of vascular dysfunction, the first step to cardiovascular disease and influencing vascular outcomes in the elderly. Accordingly, the preservation of endothelial function is thought to be an essential determinant of healthy aging. With special attention on the effects of aging on the endothelial function, this review is focused on the two main mechanisms of aging-related endothelial dysfunction: oxidative stress and inflammation. Aging vasculature generates an excess of the reactive oxygen species (ROS), superoxide and hydrogen peroxide, that compromise the vasodilatory activity of nitric oxide (NO) and facilitate the formation of the deleterious radical, peroxynitrite. Main sources of ROS are mitochondrial respiratory chain and NADPH oxidases, although NOS uncoupling could also account for ROS generation. In addition, reduced antioxidant response mediated by erythroid-2-related factor-2 (Nrf2) and downregulation of mitochondrial manganese superoxide dismutase (SOD2) contributes to the establishment of chronic oxidative stress in aged vessels. This is accompanied by a chronic low-grade inflammatory phenotype that participates in defective endothelial vasodilation. The redox-sensitive transcription factor, nuclear factor-κB (NF-κB), is upregulated in vascular cells from old subjects and drives a proinflammatory shift that feedbacks oxidative stress. This chronic NF-κB activation is contributed by increased angiotensin-II signaling and downregulated sirtuins and precludes adequate cellular response to acute ROS generation. Interventions targeted to recover endogenous antioxidant capacity and cellular stress response rather than exogenous antioxidants could reverse oxidative stress-inflammation vicious cycle in

  7. Metabolomic and Genomic Markers of Atherosclerosis as Related to Oxidative Stress, Inflammation, and Vascular Function in Twin Astronauts

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    Lee, Stuart M. C.; Rana, Brinda K.; Stenger, Michael B.; Sears, Dorothy D.; Smith, Scott M.; Zwart, Sara R.; Macias, Brandon R.; Hargans, Alan R.; Sharma, Kumar; De Vivo, Immaculata

    2017-01-01

    BACKGROUND: Future human space travel will consist primarily of long-duration missions onboard the International Space Station (ISS) or exploration-class missions to Mars, its moons, or nearby asteroids. Astronauts participating in long-duration missions may be at an increased risk of oxidative stress and inflammatory damage due to radiation, psychological stress, altered physical activity, nutritional insufficiency, and hyperoxia during extravehicular activity. By studying one identical twin during his 1-year ISS mission and his ground-based twin, this work extends a current NASA-funded investigation to determine whether these spaceflight factors contribute to an accelerated progression of atherosclerosis. This study of twins affords a unique opportunity to examine spaceflight-related atherosclerosis risk that is independent of the confounding factors associated with different genotypes. PURPOSE: The purpose of this investigation was to determine whether biomarkers of oxidative and inflammatory stress are elevated during and after long-duration spaceflight and determine if a relation exists between levels of these biomarkers and structural and functional indices of atherosclerotic risk measured in the carotid and brachial arteries. These physiological and biochemical data will be extended by using an exploratory approach to investigate the relationship between intermediate phenotypes and risk factors for atherosclerosis and the metabolomic signature from plasma and urine samples. Since metabolites are often the indirect products of gene expression, we simultaneously assessed gene expression and DNA methylation in leukocytes. HYPOTHESIS: We predict that, compared to the ground-based twin, the space-flown twin will experience elevated biomarkers of oxidative stress and inflammatory damage, altered arterial structure and function, accelerated telomere shortening, dysregulation of genes associated with oxidative stress and inflammation, and a metabolic profile shift

  8. Epoxygenated Fatty Acids Inhibit Retinal Vascular Inflammation.

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    Capozzi, Megan E; Hammer, Sandra S; McCollum, Gary W; Penn, John S

    2016-12-14

    The objective of the present study was to assess the effect of elevating epoxygenated fatty acids on retinal vascular inflammation. To stimulate inflammation we utilized TNFα, a potent pro-inflammatory mediator that is elevated in the serum and vitreous of diabetic patients. In TNFα-stimulated primary human retinal microvascular endothelial cells, total levels of epoxyeicosatrienoic acids (EETs), but not epoxydocosapentaenoic acids (EDPs), were significantly decreased. Exogenous addition of 11,12-EET or 19,20-EDP when combined with 12-(3-adamantane-1-yl-ureido)-dodecanoic acid (AUDA), an inhibitor of epoxide hydrolysis, inhibited VCAM-1 and ICAM-1 expression and protein levels; conversely the diol product of 19,20-EDP hydrolysis, 19,20-DHDP, induced VCAM1 and ICAM1 expression. 11,12-EET and 19,20-EDP also inhibited leukocyte adherence to human retinal microvascular endothelial cell monolayers and leukostasis in an acute mouse model of retinal inflammation. Our results indicate that this inhibition may be mediated through an indirect effect on NFκB activation. This is the first study demonstrating a direct comparison of EET and EDP on vascular inflammatory endpoints, and we have confirmed a comparable efficacy from each isomer, suggesting a similar mechanism of action. Taken together, these data establish that epoxygenated fatty acid elevation will inhibit early pathology related to TNFα-induced inflammation in retinal vascular diseases.

  9. Osteoprotegerin and biomarkers of vascular inflammation in type 2 diabetes.

    LENUS (Irish Health Repository)

    O'Sullivan, Eoin P

    2010-09-01

    Osteoprotegerin (OPG), receptor activator for nuclear factor kappa beta ligand (RANKL) and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) are newly discovered members of the tumour necrosis factor-alpha receptor superfamily. While their role in bone metabolism is well described, their function within the vasculature is poorly understood. OPG inhibits vascular calcification in vitro and high serum levels have been demonstrated in type 2 diabetes, but serum RANKL and TRAIL and their potential correlation with well-established biomarkers of subclinical vascular inflammation such as high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) have not been described.

  10. Effect of Extended-Release Niacin on High-Density Lipoprotein (HDL) Functionality, Lipoprotein Metabolism, and Mediators of Vascular Inflammation in Statin-Treated Patients

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    Yadav, Rahul; Liu, Yifen; Kwok, See; Hama, Salam; France, Michael; Eatough, Ruth; Pemberton, Phil; Schofield, Jonathan; Siahmansur, Tarza J; Malik, Rayaz; Ammori, Basil A; Issa, Basil; Younis, Naveed; Donn, Rachelle; Stevens, Adam; Durrington, Paul; Soran, Handrean

    2015-01-01

    Background The aim of this study was to explore the influence of extended-release niacin/laropiprant (ERN/LRP) versus placebo on high-density lipoprotein (HDL) antioxidant function, cholesterol efflux, apolipoprotein B100 (apoB)-containing lipoproteins, and mediators of vascular inflammation associated with 15% increase in high-density lipoprotein cholesterol (HDL-C). Study patients had persistent dyslipidemia despite receiving high-dose statin treatment. Methods and Results In a randomized double-blind, placebo-controlled, crossover trial, we compared the effect of ERN/LRP with placebo in 27 statin-treated dyslipidemic patients who had not achieved National Cholesterol Education Program-ATP III targets for low-density lipoprotein cholesterol (LDL-C). We measured fasting lipid profile, apolipoproteins, cholesteryl ester transfer protein (CETP) activity, paraoxonase 1 (PON1) activity, small dense LDL apoB (sdLDL-apoB), oxidized LDL (oxLDL), glycated apoB (glyc-apoB), lipoprotein phospholipase A2 (Lp-PLA2), lysophosphatidyl choline (lyso-PC), macrophage chemoattractant protein (MCP1), serum amyloid A (SAA) and myeloperoxidase (MPO). We also examined the capacity of HDL to protect LDL from in vitro oxidation and the percentage cholesterol efflux mediated by apoB depleted serum. ERN/LRP was associated with an 18% increase in HDL-C levels compared to placebo (1.55 versus 1.31 mmol/L, P<0.0001). There were significant reductions in total cholesterol, triglycerides, LDL cholesterol, total serum apoB, lipoprotein (a), CETP activity, oxLDL, Lp-PLA2, lyso-PC, MCP1, and SAA, but no significant changes in glyc-apoB or sdLDL-apoB concentration. There was a modest increase in cholesterol efflux function of HDL (19.5%, P=0.045), but no change in the antioxidant capacity of HDL in vitro or PON1 activity. Conclusions ERN/LRP reduces LDL-associated mediators of vascular inflammation, but has varied effects on HDL functionality and LDL quality, which may counter its HDL

  11. Extracellular vesicles as mediators of vascular inflammation in kidney disease.

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    Helmke, Alexandra; von Vietinghoff, Sibylle

    2016-03-06

    Vascular inflammation is a common cause of renal impairment and a major cause of morbidity and mortality of patients with kidney disease. Current studies consistently show an increase of extracellular vesicles (EVs) in acute vasculitis and in patients with atherosclerosis. Recent research has elucidated mechanisms that mediate vascular wall leukocyte accumulation and differentiation. This review addresses the role of EVs in this process. Part one of this review addresses functional roles of EVs in renal vasculitis. Most published data address anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis and indicate that the number of EVs, mostly of platelet origin, is increased in active disease. EVs generated from neutrophils by activation by ANCA can contribute to vessel damage. While EVs are also elevated in other types of autoimmune vasculitis with renal involvement such as systemic lupus erythematodes, functional consequences beyond intravascular thrombosis remain to be established. In typical hemolytic uremic syndrome secondary to infection with shiga toxin producing Escherichia coli, EV numbers are elevated and contribute to toxin distribution into the vascular wall. Part two addresses mechanisms how EVs modulate vascular inflammation in atherosclerosis, a process that is aggravated in uremia. Elevated numbers of circulating endothelial EVs were associated with atherosclerotic complications in a number of studies in patients with and without kidney disease. Uremic endothelial EVs are defective in induction of vascular relaxation. Neutrophil adhesion and transmigration and intravascular thrombus formation are critically modulated by EVs, a process that is amenable to therapeutic interventions. EVs can enhance monocyte adhesion to the endothelium and modulate macrophage differentiation and cytokine production with major influence on the local inflammatory milieu in the plaque. They significantly influence lipid phagocytosis and antigen presentation by

  12. Inhibition of vascular response in inflammation by crude aqueous ...

    African Journals Online (AJOL)

    Background: The root bark extract of Zanthoxylum xanthozyloides is used in folklore medicine in Ghana and Nigeria to treat inflammation. A previous pharmacological study confirmed the anti-inflammatory activity of the extract. Objective: To study the effect of the extract on vascular response in inflammation. Method: The ...

  13. Niacin Suppresses Progression of Atherosclerosis by Inhibiting Vascular Inflammation and Apoptosis of Vascular Smooth Muscle Cells.

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    Su, Gang; Sun, Guangli; Liu, Hai; Shu, Liliang; Zhang, Jingchao; Guo, Longhui; Huang, Chen; Xu, Jing

    2015-12-29

    BACKGROUND Niacin is a broad-spectrum lipid-regulating drug used for the clinical therapy of atherosclerosis; however, the mechanisms by which niacin ameliorates atherosclerosis are not clear. MATERIAL AND METHODS The effect of niacin on atherosclerosis was assessed by detection of atherosclerotic lesion area. Adhesion molecules in arterial endothelial cells were determined by using qRT-PCR and Western blot analysis. The levels of serum inflammatory cytokines in ApoE-/- mice were detected by using ELISA. We detected the expression levels of phosphorylated nuclear factors-kB (NF-κB) p65 in aortic endothelial cells of mice using Western blot analysis. Furthermore, we investigated the anti-inflammation effect and endothelium-protecting function of niacin and their regulatory mechanisms in vitro. RESULTS Niacin inhibited the progress of atherosclerosis and decreased the levels of serum inflammatory cytokines and adhesion molecules in ApoE-/- mice. Niacin suppressed the activity of NF-κB and apoptosis of vascular smooth muscle cells (VSMCs). Furthermore, niacin induced phosphorylated focal adhesion kinase (FAK) and FAK inhibitor PF-573228 reduced the level of Bcl-2 and elevated the level of cleaved caspase-3 in VSMCs. CONCLUSIONS Niacin inhibits vascular inflammation and apoptosis of VSMCs via inhibiting the NF-κB signaling and the FAK signaling pathway, respectively, thus protecting ApoE-/- mice against atherosclerosis.

  14. Nutrition, inflammation, and cognitive function.

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    Wärnberg, Julia; Gomez-Martinez, Sonia; Romeo, Javier; Díaz, Ligia-Esperanza; Marcos, Ascensión

    2009-02-01

    Inflammation, particularly low-grade chronic inflammation, appears to affect several brain functions, from early brain development to the development of neurodegenerative disorders and perhaps some psychiatric diseases. On the other hand, nutrition and dietary components and patterns have a plethora of anti- and pro-inflammatory effects that could be linked to cognitive function. Even a modest effect of nutrition on cognitive decline could have significant implications for public health. This paper summarizes the available evidence regarding inflammation as a key mechanism in cognitive function and nutritional pro- or anti-inflammatory effects with the purpose of linking the apparent disparate disciplines of nutrition, immunity, and neurology.

  15. The effects of garlic extract upon endothelial function, vascular inflammation, oxidative stress and insulin resistance in adults with type 2 diabetes at high cardiovascular risk. A pilot double blind randomized placebo controlled trial.

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    Atkin, Marc; Laight, David; Cummings, Michael H

    2016-01-01

    Endothelial dysfunction, vascular inflammation and oxidative stress have been integrally linked to the pathogenesis of both type 2 diabetes and cardiovascular disease. Aged Garlic Extract (AGE), a potent antioxidant, has been shown in previous studies to attenuate these novel risk factors in a non-diabetic population. This study tested the hypothesis that AGE may improve endothelial function, oxidative stress, vascular inflammation and insulin resistance in high risk cardiovascular subjects with type 2 diabetes. A double blind, placebo controlled crossover pilot study was performed in 26 subjects with type 2 diabetes who received 1200 mg of AGE or placebo daily for 4 weeks with a 4 week washout period. Plasma HsCRP was measured as a marker of inflammation. Plasma TAOS, blood GSH/GSSG and plasma LHP were measured as markers of oxidative stress/anti-oxidant defense. Insulin resistance was measured using the HOMA-IR method. Endothelial function was measured using change in the reflective index (RI) post-salbutamol using digital photoplethysmography and urinary albumin/creatinine ratio was measured as a biochemical surrogate. Measurements were taken at baseline and after intervention with AGE or placebo. Of the 26 patients studied (male 17, female 9), age was 61 ± 8 years (mean ± 1 SD), HbA1c 7.2 ± 1.1%, BP 130/75 ± 15.9/9.8 mmHg, total cholesterol 4.2 ± 0.81 mmol/l, triglyceride 2.11 ± 1.51 mmol/l, and HDL cholesterol 1.04 ± 0.29 mmol/l. The majority of patients were being treated with metformin (59%), aspirin (50%) and statin (96%) therapy. 36% were treated with an ACEI. There were no changes in these therapies throughout the study. Treatment with AGE had no significant effect upon the above metabolic parameters including insulin resistance. Treatment with AGE also had no significant effect on markers of endothelial function (plethysmography), oxidative stress (TAOS, GSH/GSSG, LHP) or inflammation (HsCRP). In this group of type 2 diabetic patients at high

  16. Perivascular adipose tissue, inflammation and insulin resistance: link to vascular dysfunction and cardiovascular disease.

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    Lastra, Guido; Manrique, Camila

    2015-04-01

    Obesity is a leading risk factor for the development of type 2 diabetes mellitus (DM2) and cardiovascular disease (CVD), however the underlying mechanisms still remain to be fully uncovered. It is now well accepted that dysfunctional adipose tissue in conditions of obesity is a critical source of inflammation that impacts the cardiovascular system and contributes to CVD. Although traditionally visceral adipose tissue has been linked to increased CVD risk, there is mounting interest in the role that fat accumulation around the vasculature plays in the pathogenesis of vascular dysfunction. Perivascular adipose tissue (PVAT) is in intimate contact with large, medium and small diameter arterial beds in several tissues, and has been shown to control vascular function as well as remodeling. PVAT does not merely mirror visceral adipose tissue changes seen in obesity, but has unique features that impact vascular biology. In lean individuals PVAT exerts vasodilatory and anti-inflammatory functions, however obesity results in PVAT inflammation, characterized by imbalance between pro- and anti-inflammatory cells as wells as adipokines. PVAT inflammation promotes insulin resistance in the vasculature, thus resulting in impaired insulin-mediated vasodilatory responses and vascular remodeling. In this review we address current knowledge about the mechanisms that link PVAT inflammation to insulin resistance and vascular dysfunction. Indeed, PVAT emerges as a novel type of adipose tissue that participates in the pathogenesis of CVD, independently to a large extent to visceral adipose tissue.

  17. Obesity-induced vascular inflammation involves elevated arginase activity.

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    Yao, Lin; Bhatta, Anil; Xu, Zhimin; Chen, Jijun; Toque, Haroldo A; Chen, Yongjun; Xu, Yimin; Bagi, Zsolt; Lucas, Rudolf; Huo, Yuqing; Caldwell, Ruth B; Caldwell, R William

    2017-11-01

    Obesity-induced vascular dysfunction involves pathological remodeling of the visceral adipose tissue (VAT) and increased inflammation. Our previous studies showed that arginase 1 (A1) in endothelial cells (ECs) is critically involved in obesity-induced vascular dysfunction. We tested the hypothesis that EC-A1 activity also drives obesity-related VAT remodeling and inflammation. Our studies utilized wild-type and EC-A1 knockout (KO) mice made obese by high-fat/high-sucrose (HFHS) diet. HFHS diet induced increases in body weight, fasting blood glucose, and VAT expansion. This was accompanied by increased arginase activity and A1 expression in vascular ECs and increased expression of tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), interleukin-10 (IL-10), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) mRNA and protein in both VAT and ECs. HFHS also markedly increased circulating inflammatory monocytes and VAT infiltration by inflammatory macrophages, while reducing reparative macrophages. Additionally, adipocyte size and fibrosis increased and capillary density decreased in VAT. These effects of HFHS, except for weight gain and hyperglycemia, were prevented or reduced in mice lacking EC-A1 or treated with the arginase inhibitor 2-(S)-amino-6-boronohexanoic acid (ABH). In mouse aortic ECs, exposure to high glucose (25 mM) and Na palmitate (200 μM) reduced nitric oxide production and increased A1, TNF-α, VCAM-1, ICAM-1, and MCP-1 mRNA, and monocyte adhesion. Knockout of EC-A1 or ABH prevented these effects. HFHS diet-induced VAT inflammation is mediated by EC-A1 expression/activity. Limiting arginase activity is a possible therapeutic means of controlling obesity-induced vascular and VAT inflammation.

  18. Message in a Microbottle: Modulation of Vascular Inflammation and Atherosclerosis by Extracellular Vesicles.

    Science.gov (United States)

    van der Vorst, Emiel P C; de Jong, Renske J; Donners, Marjo M P C

    2018-01-01

    Extracellular vesicles (EVs) have emerged as a novel intercellular communication system. By carrying bioactive lipids, miRNAs and proteins they can modulate target cell functions and phenotype. Circulating levels of EVs are increased in inflammatory conditions, e.g., cardiovascular disease patients, and their functional contribution to atherosclerotic disease development is currently heavily studied. This review will describe how EVs can modulate vascular cell functions relevant to vascular inflammation and atherosclerosis, particularly highlighting the role of EV-associated proteolytic activity and effector proteins involved. Furthermore, we will discuss key questions and challenges, especially for EV-based therapeutics.

  19. Message in a Microbottle: Modulation of Vascular Inflammation and Atherosclerosis by Extracellular Vesicles

    Directory of Open Access Journals (Sweden)

    Emiel P. C. van der Vorst

    2018-01-01

    Full Text Available Extracellular vesicles (EVs have emerged as a novel intercellular communication system. By carrying bioactive lipids, miRNAs and proteins they can modulate target cell functions and phenotype. Circulating levels of EVs are increased in inflammatory conditions, e.g., cardiovascular disease patients, and their functional contribution to atherosclerotic disease development is currently heavily studied. This review will describe how EVs can modulate vascular cell functions relevant to vascular inflammation and atherosclerosis, particularly highlighting the role of EV-associated proteolytic activity and effector proteins involved. Furthermore, we will discuss key questions and challenges, especially for EV-based therapeutics.

  20. Targeting local vascular and systemic consequences of inflammation on vascular and cardiac valve calcification.

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    Hénaut, Lucie; Sanchez-Nino, Maria Dolores; Aldamiz-Echevarría Castillo, Gonzalo; Sanz, Ana B; Ortiz, Alberto

    2016-01-01

    Cardiac valve calcification and vascular calcification (VC) are associated with cardiovascular mortality in the general population and in patients with chronic kidney disease (CKD). CKD, diabetes mellitus, and atherosclerosis are among the causes of systemic inflammation that are associated with VC. This review collates clinical and experimental evidence that inflammation accelerates VC progression. Specifically, we review the actions of key pro-inflammatory cytokines and inflammation-related transcription factors on VC, and the role played by senescence. Inflammatory cytokines, such as the TNF superfamily and IL-6 superfamily, and inflammation-related transcription factor NF-κB promote calcification in cultured vascular smooth muscle cells, valvular interstitial cells, or experimental animal models through direct effects, but also indirectly by decreasing circulating Fetuin A or Klotho levels. Experimental evidence suggests a causal link between inflammation and VC that would change the clinical approach to prevention and treatment of VC. However, the molecular basis remains unclear and little is known about VC in humans treated with drugs targeting inflammatory cytokines. The effect of biologicals targeting TNF-α, RANKL, IL-6, and other inflammatory mediators on VC, in addition to the impact of dietary phosphate in patients with chronic systemic inflammation, requires study.

  1. Recent advances in understanding the roles of vascular endothelial cells in allergic inflammation.

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    Shoda, Tetsuo; Futamura, Kyoko; Orihara, Kanami; Emi-Sugie, Maiko; Saito, Hirohisa; Matsumoto, Kenji; Matsuda, Akio

    2016-01-01

    Allergic disorders commonly involve both chronic tissue inflammation and remodeling caused by immunological reactions to various antigens on tissue surfaces. Due to their anatomical location, vascular endothelial cells are the final responders to interact with various exogenous factors that come into contact with the epithelial surface, such as pathogen-associated molecular patterns (PAMPs) and antigens. Recent studies have shed light on the important roles of endothelial cells in the development and exacerbation of allergic disorders. For instance, endothelial cells have the greatest potential to produce several key molecules that are deeply involved in allergic inflammation, such as periostin and thymus and activation-regulated chemokine (TARC/CCL17). Additionally, endothelial cells were recently shown to be important functional targets for IL-33--an essential regulator of allergic inflammation. Notably, almost all endothelial cell responses and functions involved in allergic inflammation are not suppressed by corticosteroids. These corticosteroid-refractory endothelial cell responses and functions include TNF-α-associated angiogenesis, leukocyte adhesion, IL-33-mediated responses and periostin and TARC production. Therefore, these unique responses and functions of endothelial cells may be critically involved in the pathogenesis of various allergic disorders, especially their refractory processes. Here, we review recent studies, including ours, which have elucidated previously unknown pathophysiological roles of vascular endothelial cells in allergic inflammation and discuss the possibility of endothelium-targeted therapy for allergic disorders. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  2. Whey Protein Lycosome Formulation Improves Vascular Functions and Plasma Lipids with Reduction of Markers of Inflammation and Oxidative Stress in Prehypertension

    Directory of Open Access Journals (Sweden)

    Ivan M. Petyaev

    2012-01-01

    Full Text Available Parameters reflecting cardiovascular health and inflammation were studied in a pilot clinical trial conducted on 40 patients with prehypertension. The patients were treated with a new proprietary formulation of a whey protein (WP isolate embedded into lycopene micelles (WPL during a 1-month period. Control groups received lycopene or WP as a singular formulation or placebo pills for the same period of time. Combined WPL formulation of whey protein and lycopene has caused multiple favorable changes in the cardiovascular function (including a tendency to the reduced systemic blood pressure, the plasma lipid profile, and the inflammatory status of patients with prehypertension, whereas singular formulations of the compounds and placebo did not have such an effect. The reduction of plasma triglycerides and cholesterol fractions and almost two-fold decline in C-reactive protein (CRP and inflammatory oxidative damage (IOD levels as well as an increase in nitric oxide (NO, tissue oxygenation (StO2, and flow-mediated dilation values constitute the most significant benefit/outcome of the treatment with the combined formulation of whey protein and lycopene. The treatment did not affect the values of ankle-brachial index (ABI, body weight, and body mass index (BMI.

  3. The Renin-Angiotensin-Aldosterone System in Vascular Inflammation and Remodeling

    Directory of Open Access Journals (Sweden)

    Maricica Pacurari

    2014-01-01

    Full Text Available The RAAS through its physiological effectors plays a key role in promoting and maintaining inflammation. Inflammation is an important mechanism in the development and progression of CVD such as hypertension and atherosclerosis. In addition to its main role in regulating blood pressure and its role in hypertension, RAAS has proinflammatory and profibrotic effects at cellular and molecular levels. Blocking RAAS provides beneficial effects for the treatment of cardiovascular and renal diseases. Evidence shows that inhibition of RAAS positively influences vascular remodeling thus improving CVD outcomes. The beneficial vascular effects of RAAS inhibition are likely due to decreasing vascular inflammation, oxidative stress, endothelial dysfunction, and positive effects on regeneration of endothelial progenitor cells. Inflammatory factors such as ICAM-1, VCAM-1, TNFα, IL-6, and CRP have key roles in mediating vascular inflammation and blocking RAAS negatively modulates the levels of these inflammatory molecules. Some of these inflammatory markers are clinically associated with CVD events. More studies are required to establish long-term effects of RAAS inhibition on vascular inflammation, vascular cells regeneration, and CVD clinical outcomes. This review presents important information on RAAS’s role on vascular inflammation, vascular cells responses to RAAS, and inhibition of RAAS signaling in the context of vascular inflammation, vascular remodeling, and vascular inflammation-associated CVD. Nevertheless, the review also equates the need to rethink and rediscover new RAAS inhibitors.

  4. Extracellular matrix inflammation in vascular cognitive impairment and dementia.

    Science.gov (United States)

    Rosenberg, Gary A

    2017-03-01

    Vascular cognitive impairment and dementia (VCID) include a wide spectrum of chronic manifestations of vascular disease related to large vessel strokes and small vessel disease (SVD). Lacunar strokes and white matter (WM) injury are consequences of SVD. The main vascular risk factor for SVD is brain hypoperfusion from cerebral blood vessel narrowing due to chronic hypertension. The hypoperfusion leads to activation and degeneration of astrocytes with the resulting fibrosis of the extracellular matrix (ECM). Elasticity is lost in fibrotic cerebral vessels, reducing the response of stiffened blood vessels in times of increased metabolic need. Intermittent hypoxia/ischaemia activates a molecular injury cascade, producing an incomplete infarction that is most damaging to the deep WM, which is a watershed region for cerebral blood flow. Neuroinflammation caused by hypoxia activates microglia/macrophages to release proteases and free radicals that perpetuate the damage over time to molecules in the ECM and the neurovascular unit (NVU). Matrix metalloproteinases (MMPs) secreted in an attempt to remodel the blood vessel wall have the undesired consequences of opening the blood-brain barrier (BBB) and attacking myelinated fibres. This dual effect of the MMPs causes vasogenic oedema in WM and vascular demyelination, which are the hallmarks of the subcortical ischaemic vascular disease (SIVD), which is the SVD form of VCID also called Binswanger's disease (BD). Unravelling the complex pathophysiology of the WM injury-related inflammation in the small vessel form of VCID could lead to novel therapeutic strategies to reduce damage to the ECM, preventing the progressive damage to the WM. © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  5. Impact of inflammation on vascular disease in hypertension.

    Science.gov (United States)

    Virdis, Agostino; Dell'Agnello, Umberto; Taddei, Stefano

    2014-07-01

    Low grade inflammation exerts a crucial pathogenic role in hypertension and cardiovascular disease. A large body of evidence indicates that innate and adaptive immune systems, and in particular T cells, are involved. A balance between T-effector lymphocytes and Treg lymphocytes represents a crucial regulatory mechanism that, when altered, favours blood pressure elevation and organ damage development. Of note, Treg lymphocytes exert important anti-inflammatory properties, whose activities guarantees vascular homeostasis and protects the vessel wall from the development of atherosclerosis. In humans, most of evidence ascertaining essential hypertension as a condition of chronic low-grade inflammatory status revealed a strict and independent association between CRP, TNF-α, IL-6 or adhesion molecules and vascular changes in essential hypertensive patients. Evidence of involvement of the immune system in vasculature from patients with hypertension or cardiovascular disease starts to appear in literature. Further investigation on immunity, including the role of T-lymphocytes, will help develop of new therapeutic targets that may improve outcomes in hypertension and cardiovascular disease and discover novel approaches in the treatment of hypertension and vascular disease. Copyright © 2014. Published by Elsevier Ireland Ltd.

  6. Comparison of Ticagrelor Versus Prasugrel for Inflammation, Vascular Function, and Circulating Endothelial Progenitor Cells in Diabetic Patients With Non-ST-Segment Elevation Acute Coronary Syndrome Requiring Coronary Stenting: A Prospective, Randomized, Crossover Trial.

    Science.gov (United States)

    Jeong, Han Saem; Hong, Soon Jun; Cho, Sang-A; Kim, Jong-Ho; Cho, Jae Young; Lee, Seung Hun; Joo, Hyung Joon; Park, Jae Hyoung; Yu, Cheol Woong; Lim, Do-Sun

    2017-08-28

    This study compared adenosine-associated pleiotropic effects of the 2 P2Y12 receptor antagonists on vascular function, systemic inflammation, and circulating endothelial progenitor cells (EPCs). Both ticagrelor and prasugrel have potent antiplatelet effects. However, only ticagrelor inhibits cellular uptake of adenosine. Using a randomized, crossover design with 10-week follow-up ticagrelor or prasugrel was administered to type 2 diabetic patients with non-ST-segment elevation acute coronary syndrome requiring stent implantation. A total of 62 patients underwent randomization in a 1:1 ratio to receive ticagrelor or prasugrel for 5 weeks followed by a direct cross over to the alternative treatment for 5 additional weeks. Brachial artery flow-mediated dilation, inflammatory markers, and number of circulating EPCs were compared. Improvement in brachial artery flow-mediated dilation was greater in the ticagrelor group (0.15 ± 0.19 mm vs. -0.03 ± 0.18 mm; p ticagrelor compared with prasugrel decreased interleukin 6 (-0.58 ± 0.43 pg/ml vs. -0.05 ± 0.24 pg/ml; p Ticagrelor compared with prasugrel significantly increased absolute numbers of circulating EPCs CD34+/KDR+ (42.5 ± 37.8 per μl vs. -28.2 ± 23.7 per μl; p ticagrelor significantly decreased inflammatory cytokines such as interleukin 6 and tumor necrosis factor alpha and increased circulating EPCs, contributing to improved arterial endothelial function in diabetic non-ST-segment elevation acute coronary syndrome patients. Thus, data support that pleiotropic effects of ticagrelor beyond its potent antiplatelet effects could contribute to additional clinical benefits. (Comparison of Ticagrelor vs. Prasugrel on Inflammation, Arterial Stiffness, Endothelial Function, and Circulating Endothelial Progenitor Cells in Diabetic Patients With Non-ST Elevation Acute Coronary Syndrome [NSTE-ACS] Requiring Coronary Stenting; NCT02487732). Copyright © 2017 American College of Cardiology Foundation. Published

  7. In vivo mapping of vascular inflammation using multimodal imaging.

    Directory of Open Access Journals (Sweden)

    Benjamin R Jarrett

    2010-10-01

    Full Text Available Plaque vulnerability to rupture has emerged as a critical correlate to risk of adverse coronary events but there is as yet no clinical method to assess plaque stability in vivo. In the search to identify biomarkers of vulnerable plaques an association has been found between macrophages and plaque stability--the density and pattern of macrophage localization in lesions is indicative of probability to rupture. In very unstable plaques, macrophages are found in high densities and concentrated in the plaque shoulders. Therefore, the ability to map macrophages in plaques could allow noninvasive assessment of plaque stability. We use a multimodality imaging approach to noninvasively map the distribution of macrophages in vivo. The use of multiple modalities allows us to combine the complementary strengths of each modality to better visualize features of interest. Our combined use of Positron Emission Tomography and Magnetic Resonance Imaging (PET/MRI allows high sensitivity PET screening to identify putative lesions in a whole body view, and high resolution MRI for detailed mapping of biomarker expression in the lesions.Macromolecular and nanoparticle contrast agents targeted to macrophages were developed and tested in three different mouse and rat models of atherosclerosis in which inflamed vascular plaques form spontaneously and/or are induced by injury. For multimodal detection, the probes were designed to contain gadolinium (T1 MRI or iron oxide (T2 MRI, and Cu-64 (PET. PET imaging was utilized to identify regions of macrophage accumulation; these regions were further probed by MRI to visualize macrophage distribution at high resolution. In both PET and MR images the probes enhanced contrast at sites of vascular inflammation, but not in normal vessel walls. MRI was able to identify discrete sites of inflammation that were blurred together at the low resolution of PET. Macrophage content in the lesions was confirmed by histology.The multimodal

  8. Dual-Modality Activity-Based Probes as Molecular Imaging Agents for Vascular Inflammation

    NARCIS (Netherlands)

    Withana, N.P.; Saito, T.; Ma, X.; Garland, M.; Liu, C.; Kosuge, H.; Amsallem, M.; Verdoes, M.; Ofori, L.O.; Fischbein, M.; Arakawa, M.; Cheng, Z.; McConnell, M.V.; Bogyo, M.

    2016-01-01

    Macrophages are cellular mediators of vascular inflammation and are involved in the formation of atherosclerotic plaques. These immune cells secrete proteases such as matrix metalloproteinases and cathepsins that contribute to disease formation and progression. Here, we demonstrate that

  9. Clustering of Insulin Resistance With Vascular Dysfunction and Low-Grade Inflammation in Type 2 Diabetes

    National Research Council Canada - National Science Library

    Andrea Natali; Elena Toschi; Stephanie Baldeweg; Demetrio Ciociaro; Stefania Favilla; Luigi Saccà; Ele Ferrannini

    2006-01-01

    Clustering of Insulin Resistance With Vascular Dysfunction and Low-Grade Inflammation in Type 2 Diabetes Andrea Natali 1 , Elena Toschi 1 , Stephanie Baldeweg 2 , Demetrio Ciociaro 1 , Stefania Favilla 1 , Luigi Saccà...

  10. Increased vascular inflammation in early menopausal women is associated with hot flush severity.

    Science.gov (United States)

    Bechlioulis, Aris; Naka, Katerina K; Kalantaridou, Sophia N; Kaponis, Apostolos; Papanikolaou, Odysseas; Vezyraki, Patra; Kolettis, Theofilos M; Vlahos, Antonis P; Gartzonika, Konstantina; Mavridis, Anestis; Michalis, Lampros K

    2012-05-01

    Menopause has been related to an increased atherosclerotic risk. Presence and severity of hot flushes in menopausal women have been associated with impaired endothelial function and advanced subclinical atherosclerosis. The objective of the study was to evaluate the effect of menopausal transition on vascular inflammation indices and investigate the association of hot flush severity with these indices in early menopausal women. This was a cross-sectional study that included 120 early menopausal women (age range 42-55 yr, women (controls). Serum high-sensitivity C-reactive protein, P-selectin, and soluble CD40 ligand (sCD40L) levels were measured. P-selectin and sCD40L were increased in early menopausal compared with control women (P = 0.006 and P = 0.02 respectively), whereas high-sensitivity C-reactive protein levels did not differ (P = 0.4) between the groups. Hot flush severity was the most important independent predictor of P-selectin levels (P = 0.011) in early menopausal women. Women with moderate/severe/very severe hot flushes had increased P-selectin compared with women with no/mild hot flushes or controls (P women with moderate/severe/very severe hot flushes compared with controls (P = 0.03) but did not differ significantly compared with women with no/mild hot flushes (P = 0.2). Increased indices of vascular inflammation in early menopausal compared with age-matched premenopausal women may indicate a higher atherosclerotic risk. Increased severity of hot flushes was associated with adverse changes in vascular inflammation, further supporting the emerging role of hot flushes in cardiovascular prognosis in these women.

  11. Vascular function in health, hypertension, and diabetes

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Gliemann, Lasse; Hellsten, Ylva

    2015-01-01

    muscle, which can affect muscle function. Central aspects in the vascular impairments are alterations in the formation of prostacyclin, the bioavailability of NO and an increased formation of vasoconstrictors and reactive oxygen species (ROS). Regular physical activity effectively improves vascular...... to the formation of vasodilators such as nitric oxide (NO) and prostacyclin. In essential hypertension and type II diabetes, the endothelial function and regulation of vascular tone is impaired with consequent increases in peripheral vascular resistance and inadequate regulation of oxygen supply to the skeletal...

  12. Nut consumption for vascular health and cognitive function.

    Science.gov (United States)

    Barbour, Jayne A; Howe, Peter R C; Buckley, Jonathan D; Bryan, Janet; Coates, Alison M

    2014-06-01

    Nuts are rich in many nutrients that can benefit multiple cardiometabolic functions, including arterial compliance, blood pressure, inflammation, glucoregulation and endothelial vasodilatation. Impaired vasodilatation may contribute to impaired cognitive performance due to poor cerebral perfusion. The present narrative review examines associations between nut consumption, vascular health and cognitive function. It includes a systematic search which identified seventy-one epidemiological or intervention studies in which effects of chronic nut consumption on blood pressure, glucoregulation, endothelial vasodilator function, arterial compliance, inflammatory biomarkers and cognitive performance were evaluated. Weighted mean changes were estimated where data were available; they indicate that nut consumption reduces blood pressure and improves glucoregulation, endothelial vasodilator function and inflammation, whilst a limited number of studies suggest that nut consumption may also improve cognitive performance. Further clinical trials are warranted to explore relationships between nut consumption, endothelial function and cognitive function.

  13. Inflammation and vascular responses to acute mental stress : implications for the triggering of myocardial infarction

    NARCIS (Netherlands)

    Paine, N.J.; Bosch, J.A.; Veldhuijzen Van Zanten, J.J.C.S.

    2012-01-01

    There is evidence that mental stress can trigger myocardial infarction. Even though the underlying mechanisms remain to be determined, both inflammation and vascular responses to mental stress have been implicated as contributing factors. This review explores the effects of inflammation on the

  14. PINK1 and its familial Parkinson's disease-associated mutation regulate brain vascular endothelial inflammation.

    Science.gov (United States)

    Yunfu, Wang; Guangjian, Liu; Ping, Zhong; Yanpeng, Sun; Xiaoxia, Fang; Wei, Hu; Jiang, Yuan; Jingquan, Hu; Songlin, Wang; Hongyan, Zhang; Yong, Liu; Shi, Chen

    2014-05-01

    Parkinson's disease (PD) is a debilitating disorder that affects movement. Inflammation-mediated endothelial dysfunction has been found to be involved in neurodegenerative diseases, including PD. More than 40 PTEN-induced putative kinase 1 (PINK1) mutations have been found in PD patients. The effects of PINK1 in vascular inflammation are as yet unknown. In this study, our findings revealed that PINK1 can be increased by the inflammatory cytokine tumor necrosis factor-α in primary human brain microvascular endothelial cells (HBMECs). We found that wild-type PINK1 prevents expression of the adhesion molecule vascular cell adhesion molecule-1 (VCAM-1), thus inhibiting the attachment of monocytes to brain endothelial cells. However, PINK1G309D, the loss-of-function mutation associated with early-onset familial PD, promotes expression of VCAM-1 and exacerbates attachment of monocytes to brain endothelial cells. Mechanism studies revealed that overexpression of wild-type PINK1 inhibits the VCAM-1 promoter by inhibiting the transcriptional activity of interferon regulatory factor 1 (IRF-1). However, PINK1G309D promotes the VCAM-1 promoter by increasing the transcriptional activity of IRF-1.

  15. Short-term Physical Inactivity Impairs Vascular Function

    Science.gov (United States)

    Nosova, Emily V.; Yen, Priscilla; Chong, Karen C.; Alley, Hugh F.; Stock, Eveline O.; Quinn, Alex; Hellmann, Jason; Conte, Michael S.; Owens, Christopher D.; Spite, Matthew; Grenon, S. Marlene

    2014-01-01

    Introduction Sedentarism, also termed physical inactivity, is an independent risk factor for cardiovascular diseases. Mechanisms thought to be involved include insulin resistance, dyslipidemia, hypertension, and increased inflammation. It is unknown whether changes in vascular and endothelial function also contribute to this excess risk. We hypothesized that short-term exposure to inactivity would lead to endothelial dysfunction, arterial stiffening and increased vascular inflammation. Methods Five healthy subjects (4 males and 1 female) underwent 5 days of bed rest (BR) to simulate inactivity. Measurements of vascular function [flow-mediated vasodilation (FMD) to evaluate endothelial function; applanation tonometry to assess arterial resistance], inflammation and metabolism were made before BR, daily during BR and after 2 recovery days. Subjects maintained an isocaloric diet throughout. Results Bed rest led to significant decreases in brachial artery and femoral artery FMD [Brachial: 11 ± 3% pre-BR vs. 9 ± 2% end-BR, P=0.04; Femoral: 4 ± 1% vs. 2 ± 1%, P=0.04]. The central augmentation index increased with BR [−4 ± 9% vs. 5 ± 11%, P=0.03]. Diastolic blood pressure (DBP) increased [58 ± 7 mmHg vs. 62 ± 7 mmHg, P=0.02], while neither systolic blood pressure nor heart rate changed. 15-HETE, an arachidonic acid metabolite, increased but the other inflammatory and metabolic biomarkers were unchanged. Conclusions Our findings show that acute exposure to sedentarism results in decreased endothelial function, arterial stiffening, increased DBP, and an increase in 15-HETE. We speculate that inactivity promotes a vascular “deconditioning” state characterized by impaired endothelial function, leading to arterial stiffness and increased arterial tone. Although physiologically significant, the underlying mechanisms and clinical relevance of these findings need to be further explored. PMID:24630521

  16. Vascular smooth muscle function: defining the diabetic vascular phenotype.

    Science.gov (United States)

    Bruno, Rosa Maria; Ghiadoni, Lorenzo

    2013-10-01

    In this issue of Diabetologia, a meta-analysis performed by Montero and co-authors (Diabetologia doi 10.1007/s00125-013-2974-1 ) demonstrates a significant impairment of vascular smooth muscle (VSM) function in type 2 diabetic patients. Endothelial function and VSM function between type 2 diabetic and healthy individuals were associated, especially in the microcirculation, confirming the hypothesis that unresponsiveness of VSM cells to NO may amplify the consequences of reduced NO availability. This study suggests a novel interpretation for endothelial dysfunction in diabetic patients, indicating VSM cells as key players. Causative mechanisms of VSM dysfunction, which seems to be a feature of the vascular phenotype of type 2 diabetes mellitus, are largely unexplored in humans. Future studies should also address the crucial issue of the prognostic significance of VSM dysfunction in diabetic patients, and possibly in other conditions characterised by high cardiovascular risk.

  17. Vasoreactivity, Inflammation and vascular effects of Thiazolidinediones in Insulin resistance

    NARCIS (Netherlands)

    Martens, Fabrice Marcel Anne Clément

    2006-01-01

    In the pathophysiology of atherosclerosis, based on the respons to injury mechanism, the pathophysiological phenomenons endothelial dysfunction and inflammation are playing a pivitol role. Endothelial dysfunction is characterized by a shift towards reduced vasodilation, a pro-inflammatory state,

  18. Regulation of Vascular Function on Posttranscriptional Level

    Directory of Open Access Journals (Sweden)

    Andreas Eisenreich

    2013-01-01

    Full Text Available Posttranscriptional control of gene expression is crucial for regulating plurality of proteins and functional plasticity of the proteome under (pathophysiologic conditions. Alternative splicing as well as micro (miRNA-mediated mechanisms play an important role for the regulation of protein expression on posttranscriptional level. Both alternative splicing and miRNAs were shown to influence cardiovascular functions, such as endothelial thrombogenicity and the vascular tone, by regulating the expression of several vascular proteins and their isoforms, such as Tissue Factor (TF or the endothelial nitric oxide synthase (eNOS. This review will summarize and discuss the latest findings on the (pathophysiologic role of alternative splicing processes as well as of miRNAs on modulation of vascular functions, such as coagulation, thrombosis, and regulation of the vascular tone.

  19. Vascular access versus the effect of statins on inflammation and fibrinolysis in renal dialysis patients.

    Science.gov (United States)

    do Sameiro Faria, Maria; Ribeiro, Sandra; Rocha-Pereira, Petronila; Miranda, Vasco; Quintanilha, Alexandre; Reis, Flávio; Costa, Elísio; Belo, Luís; Santos-Silva, Alice

    2013-01-01

    The aim of this work was to assess the effect of statin therapy on inflammatory and fibrinolytic/endothelial (dys)function markers in end-stage renal disease (ESRD) patients under hemodialysis (HD), according to the type of vascular access. This transversal study includes 191 ESRD patients under regular HD, divided into four groups according to vascular access and statin therapy: 87 patients with arteriovenous fistula (AVF) and no statins (AVF-NS), 61 with AVF and statins (AVF-S), 27 with central venous dialysis catheter (CVC) and no statins (CVC-NS) and 16 with CVC and statins (CVC-S). The basic lipid profile and fibrinolytic/endothelial cell function markers were assessed. Patients with CVC presented significantly higher levels of D-dimers compared with AVF groups. CVC-NS patients also presented the highest IL-6 values, which were significantly higher than those presented by CVC-S patients. AVF-S patients presented significantly higher t-PA and PAI-1 values and lower adiponectin levels compared with AVF-NS. Our results demonstrate that patients with CVC, particularly those not under statin therapy, present a higher production and turnover of fibrin. We also found that statin therapy decreases inflammation in CVC patients but is associated with a reduction of adiponectin and increased endothelial function marker levels in AVF patients.

  20. l-Homocysteine-induced cathepsin V mediates the vascular endothelial inflammation in hyperhomocysteinaemia.

    Science.gov (United States)

    Leng, Yi-Ping; Ma, Ye-Shuo; Li, Xiao-Gang; Chen, Rui-Fang; Zeng, Ping-Yu; Li, Xiao-Hui; Qiu, Cheng-Feng; Li, Ya-Pei; Zhang, Zhen; Chen, Alex F

    2017-06-20

    Vascular inflammation, including the expression of inflammatory cytokines in endothelial cells, plays a critical role in hyperhomocysteinaemia-associated vascular diseases. Cathepsin V, specifically expressed in humans, is involved in vascular diseases through its elastolytic and collagenolytic activities. The aim of this study was to determine the effects of cathepsin V on l-homocysteine-induced vascular inflammation. A high methionine diet-induced hyperhomocysteinaemic mouse model was used to assess cathepsin V expression and vascular inflammation. Cultures of HUVECs were challenged with l-homocysteine and the cathepsin L/V inhibitor SID to assess the pro-inflammatory effects of cathepsin V. Transfection and antisense techniques were utilized to investigate the effects of cathepsin V on the dual-specificity protein phosphatases (DUSPs) and MAPK pathways. Cathepsin L (human cathepsin V homologous) was increased in the thoracic aorta endothelial cells of hyperhomocysteinaemic mice; l-homocysteine promoted cathepsin V expression in HUVECs. SID suppressed the activity of cathepsin V and reversed the up-regulation of inflammatory cytokines (IL-6, IL-8 and TNF-α), adhesion and chemotaxis of leukocytes and vascular inflammation induced by l-homocysteine in vivo and in vitro. Increased cathepsin V promoted the degradation of DUSP6 and DUSP7, phosphorylation and subsequent nuclear translocation of ERK1/2, phosphorylation of STAT1 and expression of IL-6, IL-8 and TNF-α. This study has identified a novel mechanism, which shows that l-homocysteine-induced upregulation of cathepsin V mediates vascular endothelial inflammation under high homocysteine condition partly via ERK1/2 /STAT1 pathway. This mechanism could represent a potential therapeutic target in hyperaemia-associated vascular diseases. © 2017 The British Pharmacological Society.

  1. Advanced atherosclerosis is associated with inflammation, vascular dysfunction and oxidative stress, but not hypertension.

    Science.gov (United States)

    Dinh, Quynh N; Chrissobolis, Sophocles; Diep, Henry; Chan, Christopher T; Ferens, Dorota; Drummond, Grant R; Sobey, Christopher G

    2017-02-01

    Although hypertension may involve underlying inflammation, it is unknown whether advanced atherosclerosis - a chronic inflammatory condition - can by itself promote hypertension. We thus tested if advanced atherosclerosis in chronically hypercholesterolemic mice is associated with systemic and end-organ inflammation, vascular dysfunction and oxidative stress, and whether blood pressure is higher than in control mice. Male ApoE -/- and wild-type (C57Bl6J) mice were placed on a high fat or chow diet, respectively, from 5 to 61 weeks of age. Expression of several cytokines (including IL-6, TNF-α, IFN-γ and/or IL-1β) was elevated in plasma, brain, and aorta of ApoE -/- mice. Aortic superoxide production was ∼3.5-fold greater, and endothelium-dependent relaxation was markedly reduced in aorta and mesenteric artery of ApoE -/- versus wild-type mice. There was no difference in blood pressure of aged ApoE -/- (104±3mmHg, n=13) and wild-type mice (113±1mmHg, n=18). To clarify any effects of aging alone, findings from 61 week-old wild-type mice were compared with those from young (8-12 weeks old) chow-fed wild-type mice. The data indicate that aging alone increased renal and aortic expression of numerous cytokines (including CCL2, CCL7 and IL-1β). Aging had no effect on blood pressure, systemic inflammation, oxidative stress or endothelial function. Despite systemic and end-organ inflammation, oxidative stress and endothelial dysfunction, advanced atherosclerosis does not necessarily result in elevated blood pressure. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  2. Small RNA-seq during acute maximal exercise reveal RNAs involved in vascular inflammation and cardiometabolic health: brief report.

    Science.gov (United States)

    Shah, Ravi; Yeri, Ashish; Das, Avash; Courtright-Lim, Amanda; Ziegler, Olivia; Gervino, Ernest; Ocel, Jeffrey; Quintero-Pinzon, Pablo; Wooster, Luke; Bailey, Cole Shields; Tanriverdi, Kahraman; Beaulieu, Lea M; Freedman, Jane E; Ghiran, Ionita; Lewis, Gregory D; Van Keuren-Jensen, Kendall; Das, Saumya

    2017-12-01

    Exercise improves cardiometabolic and vascular function, although the mechanisms remain unclear. Our objective was to demonstrate the diversity of circulating extracellular RNA (ex-RNA) release during acute exercise in humans and its relevance to exercise-mediated benefits on vascular inflammation. We performed plasma small RNA sequencing in 26 individuals undergoing symptom-limited maximal treadmill exercise, with replication of our top candidate miRNA in a separate cohort of 59 individuals undergoing bicycle ergometry. We found changes in miRNAs and other ex-RNAs with exercise (e.g., Y RNAs and tRNAs) implicated in cardiovascular disease. In two independent cohorts of acute maximal exercise, we identified miR-181b-5p as a key ex-RNA increased in plasma after exercise, with validation in a separate cohort. In a mouse model of acute exercise, we found significant increases in miR-181b-5p expression in skeletal muscle after acute exercise in young (but not older) mice. Previous work revealed a strong role for miR-181b-5p in vascular inflammation in obesity, insulin resistance, sepsis, and cardiovascular disease. We conclude that circulating ex-RNAs were altered in plasma after acute exercise target pathways involved in inflammation, including miR-181b-5p. Further investigation into the role of known (e.g., miRNA) and novel (e.g., Y RNAs) RNAs is warranted to uncover new mechanisms of vascular inflammation on exercise-mediated benefits on health.NEW & NOTEWORTHY How exercise provides benefits to cardiometabolic health remains unclear. We performed RNA sequencing in plasma during exercise to identify the landscape of small noncoding circulating transcriptional changes. Our results suggest a link between inflammation and exercise, providing rich data on circulating noncoding RNAs for future studies by the scientific community. Copyright © 2017 the American Physiological Society.

  3. Blood flow restricted exercise and vascular function.

    Science.gov (United States)

    Horiuchi, Masahiro; Okita, Koichi

    2012-01-01

    It is established that regular aerobic training improves vascular function, for example, endothelium-dependent vasodilatation and arterial stiffness or compliance and thereby constitutes a preventative measure against cardiovascular disease. In contrast, high-intensity resistance training impairs vascular function, while the influence of moderate-intensity resistance training on vascular function is still controversial. However, aerobic training is insufficient to inhibit loss in muscular strength with advancing age; thus, resistance training is recommended to prevent sarcopenia. Recently, several lines of study have provided compelling data showing that exercise and training with blood flow restriction (BFR) leads to muscle hypertrophy and strength increase. As such, BFR training might be a novel means of overcoming the contradiction between aerobic and high-intensity resistance training. Although it is not enough evidence to obtain consensus about impact of BFR training on vascular function, available evidences suggested that BFR training did not change coagulation factors and arterial compliance though with inconsistence results in endothelial function. This paper is a review of the literature on the impact of BFR exercise and training on vascular function, such as endothelial function, arterial compliance, or other potential factors in comparison with those of aerobic and resistance training.

  4. Blood Flow Restricted Exercise and Vascular Function

    Directory of Open Access Journals (Sweden)

    Masahiro Horiuchi

    2012-01-01

    Full Text Available It is established that regular aerobic training improves vascular function, for example, endothelium-dependent vasodilatation and arterial stiffness or compliance and thereby constitutes a preventative measure against cardiovascular disease. In contrast, high-intensity resistance training impairs vascular function, while the influence of moderate-intensity resistance training on vascular function is still controversial. However, aerobic training is insufficient to inhibit loss in muscular strength with advancing age; thus, resistance training is recommended to prevent sarcopenia. Recently, several lines of study have provided compelling data showing that exercise and training with blood flow restriction (BFR leads to muscle hypertrophy and strength increase. As such, BFR training might be a novel means of overcoming the contradiction between aerobic and high-intensity resistance training. Although it is not enough evidence to obtain consensus about impact of BFR training on vascular function, available evidences suggested that BFR training did not change coagulation factors and arterial compliance though with inconsistence results in endothelial function. This paper is a review of the literature on the impact of BFR exercise and training on vascular function, such as endothelial function, arterial compliance, or other potential factors in comparison with those of aerobic and resistance training.

  5. Phytochemical genistein in the regulation of vascular function: new insights.

    Science.gov (United States)

    Si, Hongwei; Liu, Dongmin

    2007-01-01

    Genistein, a natural bioactive compound derived from legumes, has drawn wide attention during the last decade because of its potentially beneficial effects on some human degenerative diseases. It has a weak estrogenic effect and is a well-known non-specific tyrosine kinase inhibitor at pharmacological doses. Epidemiological studies show that genistein intake is inversely associated with the risk of cardiovascular diseases. Data from animal and in vitro studies suggest a protective role of genistein in cardiovascular events. However, the mechanisms of the genistein action on vascular protective effects are unclear. Past extensive studies exploring its hypolipidemic effect resulted in contradictory data. Genistein also is a relatively poor antioxidant. However, genistein protects against pro-inflammatory factor-induced vascular endothelial barrier dysfunction and inhibits leukocyte-endothelium interaction, thereby modulating vascular inflammation, a major event in the pathogenesis of atherosclerosis. Recent studies found that genistein exerts a novel non-genomic action by targeting on important signaling molecules in vascular endothelial cells (ECs). Genistein rapidly activates endothelial nitric oxide synthase and production of nitric oxide in ECs. This genistein effect is novel since it is independent of its known effects, but mediated by the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) cascade. Further studies demonstrated that genistein directly stimulates the plasma membrane-associated adenylate cyclases, leading to activation of the cAMP signaling pathway. In addition, genistein activates peroxisome proliferator-activated receptors, ligand-activated nuclear receptors important to normal vascular function. Furthermore, genistein reduces reactive oxygen species (ROS) by attenuating the expression of ROS-producing enzymes. These new findings reveal the novel roles for genistein in the regulation of vascular function and provide a basis for further

  6. Perspectives in inflammation, neoplasia, and vascular cell biology

    Energy Technology Data Exchange (ETDEWEB)

    Edgington, T.S.; Ross, R.; Silverstein, S.C.

    1987-01-01

    This book contains 25 selections. Some of the titles are: Characterization of cDNAs for the Human Interleukin-2 Receptor; Regulation of the Epidermal Growth Factor Receptor by Phosphorylation; Endothelial Cell Proteases and Cellular Invasion; Structure and Chromosomal Localization of the Human Lymphotoxin Gene; and Vascular Endothelial Cells in Cell-Mediated Immunity: Adoptive Transfer with In Vitro Conditioned Cells is Genetically Restricted at the Endothelial Cell Barrier.

  7. Cytoskeleton, cytoskeletal interactions, and vascular endothelial function

    Directory of Open Access Journals (Sweden)

    Wang J

    2012-12-01

    Full Text Available Jingli Wang,1 Michael E Widlansky1,21Department of Medicine, Cardiovascular Medicine Division, 2Department of Pharmacology, Medical College of Wisconsin, Milwaukee, Wisconsin, USAAbstract: Far from being inert, the vascular endothelium is a critical regulator of vascular function. While the endothelium participates in autocrine, paracrine, and endocrine signaling, it also transduces mechanical signals from the cell surface involving key cell structural elements. In this review, we discuss the structure of the vascular endothelium and its relationship to traditional cardiovascular risk factors and clinical cardiovascular events. Further, we review the emerging evidence that cell structural elements, including the glycocalyx, intercellular junctions, and cytoskeleton elements, help the endothelium to communicate with its environment to regulate vascular function, including vessel permeability and signal transduction via nitric oxide bioavailability. Further work is necessary to better delineate the regulatory relationships between known key regulators of vascular function and endothelial cell structural elements.Keywords: endothelium, shear stress, eNOS, cardiovascular risk factors, glycocalyx

  8. The relationship between duration of psoriasis, vascular inflammation, and cardiovascular events

    DEFF Research Database (Denmark)

    Egeberg, Alexander; Skov, Lone; Joshi, Aditya A

    2017-01-01

    BACKGROUND: Psoriasis is associated with risk of cardiovascular (CV) disease (CVD) and a major adverse CV event (MACE). Whether psoriasis duration affects risk of vascular inflammation and MACEs has not been well characterized. OBJECTIVES: We utilized two resources to understand the effect of pso...

  9. Berberine Attenuates Vascular Remodeling and Inflammation in a Rat Model of Metabolic Syndrome.

    Science.gov (United States)

    Li, Xiao-Xing; Li, Chuan-Bao; Xiao, Jie; Gao, Hai-Qing; Wang, He-Wen; Zhang, Xin-Yu; Zhang, Cheng; Ji, Xiao-Ping

    2015-01-01

    Berberine is a natural product that shows benefits for metabolic syndrome (MS). However, the effects of berberine on the improvement of vascular inflammation and remodeling in MS remain unclear. This study aimed to investigate whether berberine could prevent vascular remodeling and inflammation in the MS condition. A rat model of MS was established, and MS rats were divided into two groups: MS group without berberine treatment, and MSB group with berberine treatment (each group n-10). Ten normal Wistar rats were used as controls (NC group). Vascular damage was examined by transmission electron microscopy and pathological staining. Compared to the NC group, the secretion of inflammatory factors was increased and the aortic wall thicker in the MS group. The MSB group exhibited decreased secretion of inflammatory factors and improved vascular remodeling, compared to the MS group. In addition, the levels of p38 mitogen-activated protein kinase (p38 MAPK), activating transcription factor 2 (ATF-2) and matrix metalloproteinase 2 (MMP-2) were significantly decreased in the MSB group compared to the MS group. In conclusion, our data show that berberine improves vascular inflammation and remodeling in the MS condition, and this is correlated with the ability of berberine to inhibit p38 MAPK activation, ATF-2 phosphorylation, and MMP-2 expression.

  10. Vascular Inflammation: A Novel Access Route for Nanomedicine.

    Science.gov (United States)

    Molinaro, Roberto; Boada, Christian; Del Rosal, Guillermo Medrano; Hartman, Kelly A; Corbo, Claudia; Andrews, Elizabeth D; Toledano-Furman, Naama E; Cooke, John P; Tasciotti, Ennio

    2016-09-01

    Despite an improved understanding of its pathophysiology and a wide range of new treatments, cardiovascular disease (CVD) remains a serious public health issue and the number one cause of mortality in the United States. Conditions that promote chronic systemic inflammation, such as obesity, cancer, and autoimmune and infectious diseases, are now known to play an important role in promoting CVD by inducing the expression of endothelial adhesion molecules and chemokines; these in turn promote leukocyte adherence and infiltration, which initiates and spurs the progression of CVD. In response to this new understanding, researchers are evaluating the potential cardiovascular benefits of new-generation therapies based on endogenous molecules with anti-inflammatory properties. Similarly, targeted approaches that leverage the phenotypic differences between non-inflamed and inflamed endothelia have the potential to selectively deliver therapeutics and decrease the morbidity and mortality of CVD patients. In this review, we discuss the role of inflammation in CVD and explore the therapeutic potential of targeting inflamed vasculature through conventional and biomimetic approaches.

  11. Spray-dried plasma and fresh frozen plasma modulate permeability and inflammation in vitro in vascular endothelial cells.

    Science.gov (United States)

    Wataha, K; Menge, T; Deng, X; Shah, A; Bode, A; Holcomb, J B; Potter, D; Kozar, R; Spinella, P C; Pati, S

    2013-01-01

    After major traumatic injury, patients often require multiple transfusions of fresh frozen plasma (FFP) to correct coagulopathy and to reduce bleeding. A spray-dried plasma (SDP) product has several logistical benefits over FFP use in trauma patients with coagulopathy. These benefits include ease of transport, stability at room temperature, and rapid reconstitution for infusion. Our past work suggests that FFP promotes endothelial stability by inhibiting endothelial permeability. The main goal of this project is to determine if solvent-detergent-treated SDP is equivalent to FFP in inhibiting vascular endothelial cell (EC) permeability and inflammation in vitro. Furthermore, this study aimed to determine if solvent-detergent treatment and spray drying of plasma alters the protective effects of FFP on EC function. The five groups tested in our studies are the following: 1) fresh frozen-thawed plasma (FFP); 2) solvent-detergent-treated FFP; 3) solvent-detergent-treated SDP; 4) lactated Ringer's solution; and 5) Hextend. This study demonstrates that in vitro SDP and FFP equivalently inhibit vascular EC permeability, EC adherens junction breakdown, and endothelial white blood cell binding, an effect that is independent of changes in Vascular Cell Adhesion Molecule 1, Intracellular Adhesion Molecule 1, or E-selectin expression on ECs. Solvent-detergent treatment of FFP does not alter the protective effects of FFP on endothelial cell function in vitro. These data suggest the equivalence of FFP and SDP on modulation of endothelial function and inflammation in vitro. © 2013 American Association of Blood Banks.

  12. Retinal vascular caliber is associated with cardiovascular biomarkers of oxidative stress and inflammation: the POLA study.

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    Vincent Daien

    Full Text Available PURPOSE: Retinal vascular caliber has been linked with increased cardiovascular risk and is predictive of cardiovascular pathology, including stroke and coronary heart disease. Oxidative stress, as well as inflammatory mechanisms, plays a major role in the pathogenesis and progression of atherosclerosis, plaque rupture and vascular thrombotic propensity. The purpose of this study is to explore the relationship between retinal vascular calibers and biomarkers of oxidative stress and inflammation, in subjects free of cardiovascular pathology. PATIENTS AND METHODS: Cross-sectional analysis from a community-dwelling cohort comprising 1224 individuals aged 60 years and over, without a history of coronary or peripheral artery disease or stroke. Retinal vascular caliber was measured from fundus photographs using semi-automated standardized imaging software. Oxidative stress was evaluated using plasma superoxide dismutase 2 and glutathione peroxidase (GPx-3 activities, and inflammatory state was assessed using plasma high sensitivity C-reactive protein (hsCRP and orosomucoid. RESULTS: In a multivariate model controlling for cardiovascular risk factors, larger retinal arteriolar caliber was independently related to higher level of GPx-3 activity (p = 0.003 whereas larger venular caliber was associated with higher levels of hsCRP (p = 0.0001 and orosomucoid (p = 0.01. CONCLUSION: In the present study, biomarkers of oxidative stress regulation and inflammation were independently associated with retinal vascular calibers. This suggests that an assessment of retinal vessels may offer early and non-invasive detection of subclinical vascular pathology.

  13. Endothelial microparticles: Sophisticated vesicles modulating vascular function

    Science.gov (United States)

    Curtis, Anne M; Edelberg, Jay; Jonas, Rebecca; Rogers, Wade T; Moore, Jonni S; Syed, Wajihuddin; Mohler, Emile R

    2015-01-01

    Endothelial microparticles (EMPs) belong to a family of extracellular vesicles that are dynamic, mobile, biological effectors capable of mediating vascular physiology and function. The release of EMPs can impart autocrine and paracrine effects on target cells through surface interaction, cellular fusion, and, possibly, the delivery of intra-vesicular cargo. A greater understanding of the formation, composition, and function of EMPs will broaden our understanding of endothelial communication and may expose new pathways amenable for therapeutic manipulation. PMID:23892447

  14. In Vivo Mapping of Vascular Inflammation Using the Translocator Protein Tracer 18F-FEDAA1106

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    Simon Cuhlmann

    2014-08-01

    Full Text Available Noninvasive imaging methods are required to monitor the inflammatory content of atherosclerotic plaques. FEDAA1106 (N-(5-fluoro- 2-phenoxyphenyl-N-(2-(2-fluoroethoxy-5-methoxybenzyl acetamide is a selective ligand for TSPO-18kDa (also known as peripheral benzodiazepine receptor, which is expressed by activated macrophages. We compared 18F-FEDAA1106 and 2-deoxy-2-[18F]fluoro-D- glucose (18F-FDG, a marker of glucose metabolism for positron emission tomographic (PET imaging of vascular inflammation. This was tested using a murine model in which focal inflammation was induced in the carotid artery via placement of a constrictive cuff. Immunostaining revealed CD68-positive cells (macrophages at a disturbed flow site located downstream from the cuff. Dynamic PET imaging using 18F-FEDAA1106 or 18F-FDG was registered to anatomic data generated by computed tomographic (CT/CT angiography. Standardized uptake values were significantly increased at cuffed compared to contralateral arteries using either 18F-FEDAA1106 (p < .01 or FDG (p < .05. However, the 18F-FEDAA1106 signal was significantly higher at the inflamed disturbed flow region compared to the noninflamed uniform flow regions, whereas differences in FDG uptake were less distinct. We conclude that 18F-FEDAA1106 can be used in vivo for detection of vascular inflammation. Moreover, the signal pattern of 18F-FEDAA1106 corresponded with vascular inflammation more specifically than FDG uptake.

  15. Distinct lipid a moieties contribute to pathogen-induced site-specific vascular inflammation.

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    Connie Slocum

    2014-07-01

    Full Text Available Several successful pathogens have evolved mechanisms to evade host defense, resulting in the establishment of persistent and chronic infections. One such pathogen, Porphyromonas gingivalis, induces chronic low-grade inflammation associated with local inflammatory bone loss and systemic inflammation manifested as atherosclerosis. P. gingivalis expresses an atypical lipopolysaccharide (LPS structure containing heterogeneous lipid A species, that exhibit Toll-like receptor-4 (TLR4 agonist or antagonist activity, or are non-activating at TLR4. In this study, we utilized a series of P. gingivalis lipid A mutants to demonstrate that antagonistic lipid A structures enable the pathogen to evade TLR4-mediated bactericidal activity in macrophages resulting in systemic inflammation. Production of antagonistic lipid A was associated with the induction of low levels of TLR4-dependent proinflammatory mediators, failed activation of the inflammasome and increased bacterial survival in macrophages. Oral infection of ApoE(-/- mice with the P. gingivalis strain expressing antagonistic lipid A resulted in vascular inflammation, macrophage accumulation and atherosclerosis progression. In contrast, a P. gingivalis strain producing exclusively agonistic lipid A augmented levels of proinflammatory mediators and activated the inflammasome in a caspase-11-dependent manner, resulting in host cell lysis and decreased bacterial survival. ApoE(-/- mice infected with this strain exhibited diminished vascular inflammation, macrophage accumulation, and atherosclerosis progression. Notably, the ability of P. gingivalis to induce local inflammatory bone loss was independent of lipid A expression, indicative of distinct mechanisms for induction of local versus systemic inflammation by this pathogen. Collectively, our results point to a pivotal role for activation of the non-canonical inflammasome in P. gingivalis infection and demonstrate that P. gingivalis evades immune

  16. The relationship between duration of psoriasis, vascular inflammation, and cardiovascular events.

    Science.gov (United States)

    Egeberg, Alexander; Skov, Lone; Joshi, Aditya A; Mallbris, Lotus; Gislason, Gunnar H; Wu, Jashin J; Rodante, Justin; Lerman, Joseph B; Ahlman, Mark A; Gelfand, Joel M; Mehta, Nehal N

    2017-10-01

    Psoriasis is associated with risk of cardiovascular (CV) disease (CVD) and a major adverse CV event (MACE). Whether psoriasis duration affects risk of vascular inflammation and MACEs has not been well characterized. We utilized two resources to understand the effect of psoriasis duration on vascular disease and CV events: (1) a human imaging study and (2) a population-based study of CVD events. First, patients with psoriasis (N = 190) underwent fludeoxyglucose F 18 positron emission tomography/computed tomography (duration effect reported as a β-coefficient). Second, MACE risk was examined by using nationwide registries (adjusted hazard ratios in patients with psoriasis (n = 87,161) versus the general population (n = 4,234,793). In the human imaging study, patients were young, of low CV risk by traditional risk scores, and had a high prevalence of cardiometabolic diseases. Vascular inflammation by fludeoxyglucose F 18 positron emission tomography/computed tomography was significantly associated with disease duration (β = 0.171, P = .002). In the population-based study, psoriasis duration had strong relationship with MACE risk (1.0% per additional year of psoriasis duration [hazard ratio, 1.010; 95% confidence interval, 1.007-1.013]). These studies utilized observational data. We found detrimental effects of psoriasis duration on vascular inflammation and MACE, suggesting that cumulative duration of exposure to low-grade chronic inflammation may accelerate vascular disease development and MACEs. Providers should consider inquiring about duration of disease to counsel for heightened CVD risk in psoriasis. Copyright © 2017 American Academy of Dermatology, Inc. All rights reserved.

  17. Inflammation is Associated with Vascular Remodeling - Repairing Balances in Hypertensive Obese Subjects

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    Lies Gantini

    2011-08-01

    Full Text Available BACKGROUND: Hypertension and obesity are proinflammatory conditions. Vascular remodeling is one of the pathomechanisms reflecting increased cardiovascular (CV risks and represented as ratio of MMP-9 and sVEGFR-2 concentration. There is no association confirmed between inflammation and remodeling yet. This study was conducted to investigate the correlation between inflammation and vascular remodeling-repairing balances in hypertensive obese subjects. METHODS: This was a cross–sectional study recruited 34 hypertensive obese subjects and 10 hypertensive non obese subjects. They had no antihypertensive medications, neither diabetics nor renal disease and nor acute inflammation detected. Inflammation was assessed as increased hsCRP concentration. Vascular remodeling and repairing were consecutively represented by ratio of MMP-9 and sVEGFR-2. RESULTS: Concentration of hsCRP and MMP-9 were significantly higher in hypertensive obese group than non obese group (2.094±1.90 vs. 0.714±0.40 mg/L; p=0.029; 363.43±143.64 vs. 261.15±61.13 ng/mL, p=0.035, respectively, nonetheless no significant differences of sVEGFR-2 concentration (9.77±2.30 vs. 9.76±1.38 pg/mL, p=0.980 found in both groups. Ratio of MMP-9/sVEGFR-2 was significantly higher in hypertensive obese group than those in non-obese group (38.67±16 vs. 27.22±10, p=0.038. Likewise, they had more subjects with ratio of MMP-9/sVEGFR-2 ≥31.53. This figure is considered as cut-off point of vascular remodeling versus repairing. CONCLUSIONS: In hypertensive obese subjects, inflammation was activated and vascular remodeling more dominant than repairing process. Inflammation was associated with increased remodeling-repairing balances. KEYWORDS: matrix metalloproteinase-9 (MMP-9, soluble vascular endothelial growth factor receptor-2 (sVEGFR-2, high sensitivity C-Reactive Protein (hsCRP.

  18. The Association between Fibroblast Growth Factor-23 and Vascular Calcification Is Mitigated by Inflammation Markers

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    Mohamed M. NasrAllah

    2013-11-01

    Full Text Available Background: Fibroblast growth factor-23 (FGF-23 has been linked to vascular calcification, ventricular hypertrophy and mortality in chronic kidney disease (CKD, although these links may not be direct and independent. Similar grave outcomes are associated with inflammation and oxidative stress in CKD. Recently, accumulating evidence has linked components of phosphate homeostasis to inflammation and oxidative stress. The interaction between the triad of inflammation, FGF-23 and cardiovascular outcomes is underinvestigated. Methods: We studied 65 patients with stage 5 CKD on hemodialysis. Serum levels of FGF-23, high-sensitivity C-reactive protein (hsCRP, endogenous soluble receptor of advanced glycation end products (esRAGE, advanced oxidation protein products (AOPP, parathormone, lipids, calcium and phosphorous were measured. The aortic calcification index (ACI was determined using non-contrast CT scans of the abdominal aorta. Results: FGF-23 was elevated (mean: 4,681 pg/ml, SD: 3,906 and correlated with hsCRP, esRAGE, AOPP, dialysis vintage and phosphorus in univariate analysis. In multiple regression analysis, hsCRP, AOPP and phosphorus but not esRAGE were all significantly correlated to FGF-23 (R2 = 0.7, p 2 = 0.65, p Conclusion: FGF-23 is strongly correlated to various markers of inflammation and oxidative stress in hemodialysis patients. The association between FGF-23 and vascular calcification was mitigated when corrected for inflammation markers.

  19. Cocoa, Blood Pressure, and Vascular Function

    Science.gov (United States)

    Ludovici, Valeria; Barthelmes, Jens; Nägele, Matthias P.; Enseleit, Frank; Ferri, Claudio; Flammer, Andreas J.; Ruschitzka, Frank; Sudano, Isabella

    2017-01-01

    Cardiovascular disease (CVD) represents the most common cause of death worldwide. The consumption of natural polyphenol-rich foods, and cocoa in particular, has been related to a reduced risk of CVD, including coronary heart disease and stroke. Intervention studies strongly suggest that cocoa exerts a beneficial impact on cardiovascular health, through the reduction of blood pressure (BP), improvement of vascular function, modulation of lipid and glucose metabolism, and reduction of platelet aggregation. These potentially beneficial effects have been shown in healthy subjects as well as in patients with risk factors (arterial hypertension, diabetes, and smoking) or established CVD (coronary heart disease or heart failure). Several potential mechanisms are supposed to be responsible for the positive effect of cocoa; among them activation of nitric oxide (NO) synthase, increased bioavailability of NO as well as antioxidant, and anti-inflammatory properties. It is the aim of this review to summarize the findings of cocoa and chocolate on BP and vascular function. PMID:28824916

  20. Malnutrition and its association with inflammation and vascular disease in children on maintenance dialysis.

    Science.gov (United States)

    Canpolat, Nur; Caliskan, Salim; Sever, Lale; Tasdemir, Mehmet; Ekmekci, Ozlem Balcı; Pehlivan, Gulseren; Shroff, Rukshana

    2013-11-01

    Malnutrition is associated with both inflammation and atherosclerotic cardiovascular disease in adults with chronic kidney disease. We studied the prevalence of malnutrition and its possible associations with inflammation and vascular disease in children on chronic dialysis. Thirty-three patients on maintenance dialysis (18 peritoneal dialysis, 15 hemodialysis) and 19 age- and gender- matched healthy controls were studied. Nutritional status was assessed by anthropometric measurements including body mass index (BMI), upper arm measurements, multifrequency bioimpedance analysis (BIA) and serum levels of albumin, prealbumin, and cholesterol. Inflammation was assessed by serum levels of C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha. The carotid artery intima thickness (cIMT) was measured to assess vascular disease. Compared with healthy children, patients had lower anthropometric measurements (P Malnutrition was present in 8 (24%) and lower BIA-based fat mass was independently associated with higher IL-6 levels (P = 0.035). An increased cIMT was present in 16 (48.5%); however, there was no difference in cIMT-SDS between patients with and without malnutrition. Carotid IMT did not show any association with nutritional indices; but positively correlated with serum IL-6 (P = 0.037), CRP (P = 0.012), and iPTH (P = 0.009), and independently associated with only iPTH (P = 0.018). Children on dialysis are at an increased risk of malnutrition, inflammation, and vascular disease. Although each of these three conditions exists, there is no interaction among them all. We postulate that the malnutrition-inflammation-atherosclerosis (MIA) complex might not exist in pediatric dialysis patients.

  1. Diabetes mellitus: The linkage between oxidative stress, inflammation, hypercoagulability and vascular complications.

    Science.gov (United States)

    Domingueti, Caroline Pereira; Dusse, Luci Maria Sant'Ana; Carvalho, Maria das Graças; de Sousa, Lirlândia Pires; Gomes, Karina Braga; Fernandes, Ana Paula

    2016-01-01

    Vascular complications are the leading cause of morbidity and mortality among patients with type 1 and type 2 diabetes mellitus. These vascular abnormalities result of a chronic hyperglycemic state, which leads to an increase in oxidative stress and inflammatory responses. This review addresses the relationships among endothelial dysfunction, hypercoagulability and inflammation and their biomarkers in the development of vascular complications in type 1 and type 2 diabetes. Inflammation, endothelial dysfunction, and hypercoagulability are correlated to each other, playing an important role in the development of vascular complications in diabetic patients. Moreover, it has been observed that several endothelial, inflammatory and pro-coagulant biomarkers, such as VWF, IL-6, TNF-α, D-dimer and PAI-1, are increased in diabetic patients who have microvascular and macrovascular complications, including nephropathy or cardiovascular disease. It is promising the clinical and laboratory use of endothelial, inflammatory and pro-coagulant biomarkers for predicting the risk of cardiovascular and renal complications in diabetic patients and for monitoring these patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Inflammation and Vascular Effects after Repeated Intratracheal Instillations of Carbon Black and Lipopolysaccharide

    DEFF Research Database (Denmark)

    Christophersen, Daniel Vest; Jacobsen, Nicklas Raun; Jensen, Ditte Marie

    2016-01-01

    Inflammation and oxidative stress are considered the main drivers of vasomotor dysfunction and progression of atherosclerosis after inhalation of particulate matter. In addition, new studies have shown that particle exposure can induce the level of bioactive mediators in serum, driving vascular......-and systemic toxicity. We aimed to investigate if pulmonary inflammation would accelerate nanoparticle-induced atherosclerotic plaque progression in Apolipoprotein E knockout (ApoE-/-) mice. ApoE-/- mice were exposed to vehicle, 8.53 or 25.6 mu g nanosized carbon black (CB) alone or spiked with LPS (0.2 mu g....../mouse/exposure; once a week for 10 weeks). Inflammation was determined by counting cells in bronchoalveolar lavage fluid. Serum Amyloid A3 (Saa3) expression and glutathione status were determined in lung tissue. Plaque progression was assessed in the aorta and the brachiocephalic artery. The effect of vasoactive...

  3. Stem cell function during plant vascular development.

    Science.gov (United States)

    Elo, A; Immanen, J; Nieminen, K; Helariutta, Y

    2009-12-01

    While many regulatory mechanisms controlling the development and function of root and shoot apical meristems have been revealed, our knowledge of similar processes in lateral meristems, including the vascular cambium, is still limited. Our understanding of even the anatomy and development of lateral meristems (procambium or vascular cambium) is still relatively incomplete, let alone their genetic regulation. Research into this particular tissue type has been mostly hindered by a lack of suitable molecular markers, as well as the fact that thus far very few mutants affecting plant secondary development have been described. The development of suitable molecular markers is a high priority in order to help define the anatomy, especially the location and identity of cambial stem cells and the developmental phases and molecular regulatory mechanisms of the cambial zone. To date, most of the advances have been obtained by studying the role of the major plant hormones in vascular development. Thus far auxin, cytokinin, gibberellin and ethylene have been implicated in regulating the maintenance and activity of cambial stem cells; the most logical question in research would be how these hormones interact during the various phases of cambial development.

  4. Organ culture of C57BL/6 mouse arteries with LPS as an in vitro model of vascular inflammation

    DEFF Research Database (Denmark)

    Outzen, Emilie Middelbo; Mehryar, Rahila; Boonen, Harrie C.M.

    an in vitro model for studying vascular inflammation and function in cultured arteries from C57BL/6 mice. Methods: Segments of abdominal aorta and mesenteric arteries (MA) were incubated for 24 hours at 37̊C and 95% O2/5% CO2 in DMEM ± 100 ng/mL LPS. Aorta segments were frozen for molecular studies...... was achieved at a normalisation factor of 0.9 (0.91 ± 0.06, mean ± SEM, n = 9) as observed (0.85 ± 0.06, mean ± SEM, n = 3) and previously described in rat MA (Mulvany and Halpern, 1977). Furthermore, preliminary findings show that organ culture with 100 ng/mL LPS decreases endothelium-dependent dilation of C......57BL/6 MA along with increased expression of inflammatory markers in aorta. Conclusions: In C57BL/6 MA, maximum active wall tension was achieved with a normalisation factor of 0.9. Furthermore, organ culture with LPS induces vascular inflammation and functional changes in C57BL/6 arteries...

  5. Inflammation-regulated mRNA stability and the progression of vascular inflammatory diseases.

    Science.gov (United States)

    Herman, Allison B; Autieri, Michael V

    2017-11-15

    Cardiovascular disease remains a major medical and socioeconomic burden in developed and developing societies, and will increase with an aging and increasingly sedentary society. Vascular disease and atherosclerotic vascular syndromes are essentially inflammatory disorders, and transcriptional and post-transcriptional processes play essential roles in the ability of resident vascular and inflammatory cells to adapt to environmental stimuli. The regulation of mRNA translocation, stability, and translation are key processes of post-transcriptional regulation that permit these cells to rapidly respond to inflammatory stimuli. For the most part, these processes are controlled by elements in the 3'-UTR of labile, proinflammatory transcripts. Since proinflammatory transcripts almost exclusively contain AU-rich elements (AREs), this represents a tightly regulated and specific mechanism for initiation and maintenance of the proinflammatory phenotype. RNA-binding proteins (RBPs) recognize cis elements in 3'-UTR, and regulate each of these processes, but there is little literature exploring the concept that RBPs themselves can be directly regulated by inflammatory stimuli. Conceptually, inflammation-responsive RBPs represent an attractive target of rational therapies to combat vascular inflammatory syndromes. Herein we briefly describe the cellular and molecular etiology of atherosclerosis, and summarize our current understanding of RBPs and their specific roles in regulation of inflammatory mRNA stability. We also detail RBPs as targets of current anti-inflammatory modalities and how this may translate into better treatment for vascular inflammatory diseases. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  6. Adipose inflammation initiates recruitment of leukocytes to mouse femoral artery: role of adipo-vascular axis in chronic inflammation.

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    Sumihiko Hagita

    Full Text Available BACKGROUND: Although inflammation within adipose tissues is known to play a role in metabolic syndrome, the causative connection between inflamed adipose tissue and atherosclerosis is not fully understood. In the present study, we examined the direct effects of adipose tissue on macro-vascular inflammation using intravital microscopic analysis of the femoral artery after adipose tissue transplantation. METHODS AND RESULTS: We obtained subcutaneous (SQ and visceral (VIS adipose tissues from C57BL/6 mice fed normal chow (NC or a high fat diet (HF, then transplanted the tissues into the perivascular area of the femoral artery of recipient C57/BL6 mice. Quantitative intravital microscopic analysis revealed an increase in adherent leukocytes after adipose tissue transplantation, with VIS found to induce significantly more leukocyte accumulation as compared to SQ. Moreover, adipose tissues from HF fed mice showed significantly more adhesion to the femoral artery. Simultaneous flow cytometry demonstrated upregulation of CD11b on peripheral granulocyte and monocytes after adipose tissue transplantation. We also observed dominant expressions of the inflammatory cytokine IL-6, and chemokines MCP-1 and MIP-1β in the stromal vascular fraction (SVF of these adipose tissues as well as sera of recipient mice after transplantation. Finally, massive accumulations of pro-inflammatory and dendritic cells were detected in mice with VIS transplantation as compared to SQ, as well as in HF mice as compared to those fed NC. CONCLUSION: Our in vivo findings indicate that adipose tissue stimulates leukocyte accumulation in the femoral artery. The underlying mechanisms involve upregulation of CD11b in leukocytes, induction of cytokines and chemokines, and accumulation of pro-inflammatory cells in the SVF.

  7. EFFECTS OF PROLONGED ENDURANCE EXERCISE ON VASCULAR ENDOTHELIAL AND INFLAMMATION MARKERS

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    Haemi Jee

    2012-12-01

    Full Text Available Systemic inflammation has been found in association with vascular endothelial function for clinical implications including exercise-induced pathology. However, information on the relationship between the exercise-related inflammatory responses and endothelial function is limited. This study aimed to investigate the effects of prolonged endurance exercise on the expression of selected soluble adhesion molecules and inflammatory markers. Twenty- four middle-aged males participating in a 308 km ultra-marathon were recruited in this study. Venous blood was collected at baseline, 100 km, 200 km, and 308 km for the analysis of sVCAM-1, sE- selectin, leukocytes, hs-CRP, CK, and TNF-α. Significant increases of sVCAM-1, sE-selectin, and leukocytes were observed at 100 km. sVCAM-1 had the greatest significant increase at 100 km. In addition, sVCAM-1 was significantly associated with the running speed and leukocytes. sE-selectin was significantly associated with leukocytes, hs-CRP, TNF-α, and CK. Delayed rises in hs-CRP and CK were observed at 200 km. TNF-α fluctuated throughout the race with a significant increase at 308 km. Delayed onset of hs-CRP and continuously increased sE-selectin suggest anti-inflammatory responses to suppress pro-inflammatory markers such as TNF-α. Prolonged repetition of muscle contraction may have released delayed CK and significant rise in TNF-α toward the end of the race. The present study demonstrated an activation of the surrogate markers of endothelial dysfunction in relationship to exercise intensity and leukocyte trafficking without a significant activation of the inflammatory responses. Thus, alteration of the endothelium may be related to increased blood flow and shear stress put upon the endothelium in response to increased oxygen demand on the heart

  8. Effect of uremia on HDL composition, vascular inflammation, and atherosclerosis in wild-type mice

    DEFF Research Database (Denmark)

    Bang, Christian A; Bro, Susanne; Bartels, Emil D

    2007-01-01

    Wild-type mice normally do not develop atherosclerosis, unless fed cholic acid. Uremia is proinflammatory and increases atherosclerosis 6- to 10-fold in apolipoprotein E-deficient mice. This study examined the effect of uremia on lipoproteins, vascular inflammation, and atherosclerosis in wild-ty...... in cholic acid-fed sham mice. The results suggest that moderate uremia neither induces aortic inflammation nor atherosclerosis in C57BL/6J mice despite increased LDL/HDL cholesterol ratio and altered HDL composition.......Wild-type mice normally do not develop atherosclerosis, unless fed cholic acid. Uremia is proinflammatory and increases atherosclerosis 6- to 10-fold in apolipoprotein E-deficient mice. This study examined the effect of uremia on lipoproteins, vascular inflammation, and atherosclerosis in wild....... In NX mice fed the Western-type diet (n = 7), the total plasma cholesterol concentration was similar to that in sham mice (n = 11), but on gel filtration the LDL/HDL cholesterol ratio was increased. HDL from NX mice contained more serum amyloid A and triglycerides and less cholesterol than HDL from sham...

  9. Protective Effect of Allium tuberosum Extract on Vascular Inflammation in Tumor Necrosis Factor-α-induced Human Vascular Endothelial Cells.

    Science.gov (United States)

    Hur, Haeng Jeon; Lee, Ae Sin

    2017-12-01

    Endothelial adhesion molecule expression induced by pro-inflammatory cytokine plays an important role in vascular endothelial cell injury, leading to vascular disease. Allium tuberosum (AT), which is used as a functional food, has a thrombolytic effect. It contains vitamin A, vitamin C, carbohydrate, calcium, iron, and phosphorus. There are many carotenes that turn into vitamin A in the body. Also, it helps blood circulation and stimulates metabolism. The purpose of the this study was to estimate the anti-inflammatory effects of the AT extract. Human vascular endothelial cells were pre-treated with 100 μg/mL AT extract for 30 minutes and subsequently co-treated with TNF-α (10 ng/mL) and AT extract (100 μg/mL) for 1, 4, and 6 hours. After treatment, the cells were lysed and used for quantitative reverse transcription PCR, Western blot analysis, and monocyte adhesion assay. We examined the effect of the AT extract on inflammatory gene expression in TNF-α-induced human umbilical vein endothelial cells (HUVECs). The extract reduced the expression levels of mRNA and protein of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 in TNF-α-stimulated HUVECs. It also inhibited the TNF-α-induced phosphorylation of the NF-κB p65 subunit and degradation of IκBα. Furthermore, the AT extract prevented the increased adhesion capacity of monocyte to TNF-α-stimulated vascular endothelial cells by reducing ICAM-1 and VCAM-1 expression. The AT extract has preventive and anti-inflammatory effect against vascular disease and has potential for supporting prevention against the early process of atherosclerosis.

  10. Role of Cox-2 in Vascular Inflammation: An Experimental Model of Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Nicolás F. Renna

    2013-01-01

    Full Text Available The objective of this work was to demonstrate the role of COX-2 enzyme at the vascular in experimental model of metabolic syndrome. SHR male WKY rats were employed; they were distributed in 8 groups (n=8 each: control (W; W + L: WKY rats receiving 20 mg/kg of lumiracoxib by intraesophageal administration; SHR; SHR + L: SHR + 20 mg/kg of lumiracoxib by intraesophageal administration; Fructose-Fed Rats (FFR: WKY rats receiving 10% (w/v fructose solution in drinking water during all 12 weeks; FFR + L: FFR + 20 mg/kg of lumiracoxib by intraesophageal administration; Fructose-Fed Hypertensive Rats (FFHR: SHR receiving 10% (w/v fructose solution in drinking water during all 12 weeks; and FFHR + L: FFHR + 20 mg/kg of lumiracoxib by intraesophageal administration. Metabolic variables, blood pressure, morphometric variables, and oxidative stress variables were evaluated; also MMP-2 and MMP-9 (collagenases, VCAM-1, and NF-κB by Westernblot or IFI were evaluated. FFHR presented all variables of metabolic syndrome; there was also an increase in oxidative stress variables; vascular remodeling and left ventricular hypertrophy were evidenced along with a significant increase in the expression of the mentioned proinflammatory molecules and increased activity and expression of collagenase. Lumiracoxib was able to reverse vascular remodeling changes and inflammation, demonstrating the involvement of COX-2 in the pathophysiology of vascular remodeling in this experimental model.

  11. Role of Renin-Angiotensin system and oxidative stress on vascular inflammation in insulin resistence model.

    Science.gov (United States)

    Renna, N F; Lembo, C; Diez, E; Miatello, R M

    2013-01-01

    (1) This study aims to demonstrate the causal involvement of renin angiotensin system (RAS) and oxidative stress (OS) on vascular inflammation in an experimental model of metabolic syndrome (MS) achieved by fructose administration to spontaneously hypertensive rats (FFHR) during 12 weeks. (2) Chronic treatment with candesartan (C) (10 mg/kg per day for the last 6 weeks) or 4OH-Tempol (T) (10(-3) mmol/L in drinking water for the last 6 weeks) reversed the increment in metabolic variables and systolic blood pressure. In addition, chronic C treatment reverted cardiovascular remodeling but not T. (3) Furthermore, chronic treatment with C was able to completely reverse the expression of NF-κB and VCAM-1, but T only reduced the expression. C reduced the expression of proatherogenic cytokines as CINC2, CINC3, VEGF, Leptin, TNF-alpha, and MCP-1 and also significantly reduced MIP-3, beta-NGF, and INF-gamma in vascular tissue in this experimental model. T was not able to substantially modify the expression of these cytokines. (4) The data suggest the involvement of RAS in the expression of inflammatory proteins at different vascular levels, allowing the creation of a microenvironment suitable for the creation, perpetuation, growth, and destabilization of vascular injury.

  12. Role of Renin-Angiotensin System and Oxidative Stress on Vascular Inflammation in Insulin Resistence Model

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    N. F. Renna

    2013-01-01

    Full Text Available (1 This study aims to demonstrate the causal involvement of renin angiotensin system (RAS and oxidative stress (OS on vascular inflammation in an experimental model of metabolic syndrome (MS achieved by fructose administration to spontaneously hypertensive rats (FFHR during 12 weeks. (2 Chronic treatment with candesartan (C (10 mg/kg per day for the last 6 weeks or 4OH-Tempol (T (10−3 mmol/L in drinking water for the last 6 weeks reversed the increment in metabolic variables and systolic blood pressure. In addition, chronic C treatment reverted cardiovascular remodeling but not T. (3 Furthermore, chronic treatment with C was able to completely reverse the expression of NF-κB and VCAM-1, but T only reduced the expression. C reduced the expression of proatherogenic cytokines as CINC2, CINC3, VEGF, Leptin, TNF-alpha, and MCP-1 and also significantly reduced MIP-3, beta-NGF, and INF-gamma in vascular tissue in this experimental model. T was not able to substantially modify the expression of these cytokines. (4 The data suggest the involvement of RAS in the expression of inflammatory proteins at different vascular levels, allowing the creation of a microenvironment suitable for the creation, perpetuation, growth, and destabilization of vascular injury.

  13. Placental hemostasis and sterile inflammation: New insights into gestational vascular disease.

    Science.gov (United States)

    Kohli, Shrey; Isermann, Berend

    2017-03-01

    Activation of the coagulation and inflammatory systems are physiologically occurring during pregnancy. However, excess activation of either system is well documented in gestational vascular diseases (GVD). GVD are placenta-mediated pregnancy complications and a major cause of feto-maternal morbidity and mortality. The causal relevance of excess coagulation and inflammatory responses for GVD remains largely unknown. Deciphering the causal relationship of excess coagulation and inflammation in GVD may allow conceptualizing new therapeutic approaches to combat GVD. Platelet activation and procoagulant extracellular vesicles (EVs) provide a link between coagulation and inflammation and their activation or generation in GVD is well established. As recently shown EVs cause sterile placental inflammation by activating maternal platelets that release ATP and activate purinergic receptor signaling and NLRP3 inflammasome in the embryonic trophoblast. This thrombo-inflammatory mechanism suggests a novel link between coagulation activation and sterile inflammation in GVD. These findings highlight a role of anti-platelet therapies in GVD. In addition, targeting the inflammasome alone or in combination with platelet inhibition may provide a new therapeutic strategy in GVD. © 2017 Elsevier Ltd. All rights reserved.

  14. Genistein inhibits TNF-α-induced endothelial inflammation through the protein kinase pathway A and improves vascular inflammation in C57BL/6 mice.

    Science.gov (United States)

    Jia, Zhenquan; Babu, Pon Velayutham Anandh; Si, Hongwei; Nallasamy, Palanisamy; Zhu, Hong; Zhen, Wei; Misra, Hara P; Li, Yunbo; Liu, Dongmin

    2013-10-03

    Genistein, a soy isoflavone, has received wide attention for its potential to improve vascular function, but the mechanism of this effect is unclear. Here, we report that genistein at physiological concentrations (0.1 μM-5 μM) significantly inhibited TNF-α-induced adhesion of monocytes to human umbilical vein endothelial cells, a key event in the pathogenesis of atherosclerosis. Genistein also significantly suppressed TNF-α-induced production of adhesion molecules and chemokines such as sICAM-1, sVCAM-1, sE-Selectin, MCP-1 and IL-8, which play key role in the firm adhesion of monocytes to activated endothelial cells (ECs). Genistein at physiologically relevant concentrations didn't significantly induce antioxidant enzyme activities or scavenge free radicals. Further, blocking the estrogen receptors (ERs) in ECs didn't alter the preventive effect of genistein on endothelial inflammation. However, inhibition of protein kinase A (PKA) significantly attenuated the inhibitory effects of genistein on TNF-α-induced monocyte adhesion to ECs as well as the production of MCP-1 and IL-8. In animal study, dietary genistein significantly suppressed TNF-α-induced increase in circulating chemokines and adhesion molecules in C57BL/6 mice. Genistein treatment also reduced VCAM-1 and monocytes-derived F4/80-positive macrophages in the aorta of TNF-α-treated mice. In conclusion, genistein protects against TNF-α-induced vascular endothelial inflammation both in vitro and in vivo models. This anti-inflammatory effect of genistein is independent of the ER-mediated signaling machinery or antioxidant activity, but mediated via the PKA signaling pathway. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  15. Aging exacerbates obesity-induced oxidative stress and inflammation in perivascular adipose tissue in mice: a paracrine mechanism contributing to vascular redox dysregulation and inflammation.

    Science.gov (United States)

    Bailey-Downs, Lora C; Tucsek, Zsuzsanna; Toth, Peter; Sosnowska, Danuta; Gautam, Tripti; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

    2013-07-01

    Obesity in the elderly individuals is increasing at alarming rates and there is evidence suggesting that elderly individuals are more vulnerable to the deleterious cardiovascular effects of obesity than younger individuals. However, the specific mechanisms through which aging and obesity interact to promote the development of cardiovascular disease remain unclear. The present study was designed to test the hypothesis that aging exacerbates obesity-induced inflammation in perivascular adipose tissue, which contributes to increased vascular oxidative stress and inflammation in a paracrine manner. To test this hypothesis, we assessed changes in the secretome, reactive oxygen species production, and macrophage infiltration in periaortic adipose tissue of young (7 month old) and aged (24 month old) high-fat diet-fed obese C57BL/6 mice. High-fat diet-induced vascular reactive oxygen species generation significantly increased in aged mice, which was associated with exacerbation of endothelial dysfunction and vascular inflammation. In young animals, high-fat diet-induced obesity promoted oxidative stress in the perivascular adipose tissue, which was associated with a marked proinflammatory shift in the profile of secreted cytokines and chemokines. Aging exacerbated obesity-induced oxidative stress and inflammation and significantly increased macrophage infiltration in periaortic adipose tissue. Using cultured arteries isolated from young control mice, we found that inflammatory factors secreted from the perivascular fat tissue of obese aged mice promote significant prooxidative and proinflammatory phenotypic alterations in the vascular wall, mimicking the aging phenotype. Overall, our findings support an important role for localized perivascular adipose tissue inflammation in exacerbation of vascular oxidative stress and inflammation in aging, an effect that likely enhances the risk for development of cardiovascular diseases from obesity in the elderly individuals.

  16. Hemodynamics, inflammation, vascular remodeling, and the development and rupture of intracranial aneurysms: a review

    Directory of Open Access Journals (Sweden)

    Francesco Signorelli

    2015-06-01

    Full Text Available The central nervous system is an immunologically active environment where several components of the immune and inflammatory response interact among them and with the constituents of nervous tissue and vasculature in a critically orchestrated manner, influencing physiologic and pathologic processes. In particular, inflammation takes a central role in the pathogenesis of intracranial aneurysms (IAs. The common pathway for aneurysm formation involves endothelial dysfunction and injury, a mounting inflammatory response, vascular smooth muscle cells (VSMCs phenotypic modulation, extracellular matrix remodeling, and subsequent cell death and vessel wall degeneration. We conducted a literature review (1980-2014 by Medline and EMBASE databases using the searching terms "IA" and "cerebral aneurysm" and further search was performed to link the search terms with the following key words: inflammation, hemodynamic(s, remodeling, macrophages, neutrophils, lymphocytes, complement, VSMCs, mast cells, cytokines, and inflammatory biomarkers. The aim of this review was to summarize the most recent and pertinent evidences regarding the articulated processes of aneurysms formation, growth, and rupture. Knowledge of these processes may guide the diagnosis and treatment of these vascular malformations, the most common cause of subarachnoid hemorrhage, which prognosis remains dismal.

  17. Anti-Inflammatory effect of Buddleja officinalis on vascular inflammation in human umbilical vein endothelial cells.

    Science.gov (United States)

    Lee, Yun Jung; Moon, Mi Kyoung; Hwang, Sun Mi; Yoon, Jung Joo; Lee, So Min; Seo, Kwan Soo; Kim, Jin Sook; Kang, Dae Gill; Lee, Ho Sub

    2010-01-01

    Vascular inflammation process has been suggested to be an important risk factor in the initiation and development of atherosclerosis. In this study, we investigated whether and by what mechanisms an aqueous extract of Buddleja officinalis (ABO) inhibited the expressions of cellular adhesion molecules, which are relevant to inflammation and atherosclerosis. Pretreatment of human umbilical vein endothelial cells (HUVEC) with ABO (1-10 microg/ml) for 18 hours dose-dependently inhibited TNF-alpha-induced adhesion U937 monocytic cells, as well as mRNA and protein expressions of vascular cell adhesion molecule-1 (VCAM-1), and intercellular cell adhesion molecule-1 (ICAM-1). Pretreatment with ABO also blocked TNF-alpha-induced ROS formation. Nuclear factor-kappa B (NF-kappaB) is required in the transcription of these adhesion molecule genes. Western blot analysis revealed that ABO inhibits the translocation of the p65 subunit of NF-kappaB to the nucleus. ABO inhibited the TNF-alpha-induced degradation of IkappaB-alpha, an inhibitor of NF-kappaB, by inhibiting the phosphorylation of IkappaB-alpha in HUVEC. Taken together, ABO could reduce cytokine-induced endothelial adhesiveness throughout down-regulating intracellular ROS production, NF-kappaB, and adhesion molecule expression in HUVEC, suggesting that the natural herb Buddleja officinalis may have potential implications in atherosclerosis.

  18. Trans fatty acids induce vascular inflammation and reduce vascular nitric oxide production in endothelial cells.

    Directory of Open Access Journals (Sweden)

    Naomi G Iwata

    Full Text Available Intake of trans fatty acids (TFA, which are consumed by eating foods made from partially hydrogenated vegetable oils, is associated with a higher risk of cardiovascular disease. This relation can be explained by many factors including TFA's negative effect on endothelial function and reduced nitric oxide (NO bioavailability. In this study we investigated the effects of three different TFA (2 common isomers of C18 found in partially hydrogenated vegetable oil and a C18 isomer found from ruminant-derived-dairy products and meat on endothelial NF-κB activation and nitric oxide (NO production. Human endothelial cells were treated with increasing concentrations of Elaidic (trans-C18:1 (9 trans, Linoelaidic (trans-C18:2 (9 trans, 12 trans, and Transvaccenic (trans-C18:1 (11 trans for 3 h. Both Elaidic and Linoelaidic acids were associated with increasing NF-κB activation as measured by IL-6 levels and phosphorylation of IκBα, and impairment of endothelial insulin signaling and NO production, whereas Transvaccenic acid was not associated with these responses. We also measured superoxide production, which has been hypothesized to be necessary in fatty acid-dependent activation of NF-κB. Both Elaidic acid and Linoelaidic acid are associated with increased superoxide production, whereas Transvaccenic acid (which did not induce inflammatory responses did not increase superoxide production. We observed differential activation of endothelial superoxide production, NF-κB activation, and reduction in NO production by different C18 isomers suggesting that the location and number of trans double bonds effect endothelial NF-κB activation.

  19. Functional preservation of vascular smooth muscle tissue

    Science.gov (United States)

    Alexander, W. C.; Hutchins, P. M.; Kimzey, S. L.

    1973-01-01

    The ionic and cellular feedback relationships operating to effect the vascular decompensatory modifications were examined to reveal procedures for implementing protective measures guarding against vascular collapse when returning from a weightless environment to that of the earth's gravity. The surgical procedures for preparing the rat cremaster, and the fixation methods are described. Abstracts of publications resulting from this research are included.

  20. T lymphocytes and vascular inflammation contribute to stress-dependent hypertension.

    Science.gov (United States)

    Marvar, Paul J; Vinh, Antony; Thabet, Salim; Lob, Heinrich E; Geem, Duke; Ressler, Kerry J; Harrison, David G

    2012-05-01

    Psychological stress is a significant risk factor for hypertension and also directly affects the immune system. We have previously reported that T lymphocytes are essential for development of hypertension and that the central nervous system contributes to peripheral T-lymphocyte activation and vascular inflammation in this disease; however, the role of T-cell activation in stress-related hypertension remains unclear. Wild-type and T-cell-deficient (RAG-1(-/-)) mice were subjected to daily episodes of stress and blood pressure was measured. Circulating T-cell activation markers and vascular infiltration of immune cells were analyzed, as were stress hormone levels and gene expression changes in the brain. The effects angiotensin II infusion in the presence of chronic stress was also studied. Repeated daily stress contributed to acute elevations in blood pressure that were associated with increased activation of circulating T cells and increased vascular infiltration of T cells. Repeated stress increased blood pressure in wild-type but not RAG-1(-/-) mice. Adoptive transfer of T cells to RAG-1(-/-) mice restored blood pressure elevation in response to stress. Stress-related hypertension and vascular infiltration of T cells was markedly enhanced by angiotensin II. Moreover, angiotensin II-infused mice exposed to chronic stress exhibited greater blood pressure reactivity to an episode of acute stress. These data demonstrate that stress-dependent hypertension triggers an inflammatory response that raises blood pressure at baseline and augments the hypertension caused by angiotensin II. These data provide insight as to how psychological stress contributes to hypertension. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  1. Nanostructures to modulate vascular inflammation: Multifunctional nanoparticles for quantifiable siRNA delivery and molecular imaging

    Science.gov (United States)

    Kaneda, Megan Marie

    Early steps in the progression of inflammatory diseases such as atherosclerosis involve the recruitment of leukocytes to the vascular endothelium through the expression or up-regulation of adhesion molecules. These adhesion molecules are critical mediators of leukocyte attachment and subsequent extravasation through transendothelial migration. One of these adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) is particularly attractive as a marker of early atherosclerotic activity due to its low expression level on normal endothelium and up-regulation prior to and during the development of early lesions. With this in mind, the purpose of this thesis was to develop nanostructures for the detection and down-regulation of adhesion molecules by the vascular endothelium. To detect early inflammation we designed a perfluorocarbon nanoparticle (PFC-NP) probe, which was used for in vivo targeting of VCAM-1. Nanoparticles were detected ex vivo by the magnetic resonance (MR) signature from the fluorine core of the particle. Nanoparticles accumulated in tissues characterized by early inflammatory processes. To down-regulate VCAM-1 expression by vascular endothelial cells, cationic PFC-NP were produced through the addition of the cationic lipid 1,2-Dioleoyl-3-Trimethylammonium-Propane. Cationic PFC-NP were able to deliver anti-VCAM-1 siRNA to endothelial cells through a non-standard lipid raft mediated endocytic pathway. VCAM-1 levels were significantly reduced in treated cells indicating that this delivery mechanism may be advantageous for delivery of cargo into the cytoplasm. Using the fluorine signature from the core of the cationic PFC-NP, we were able to quantify and localize this siRNA delivery agent both in vitro and in vivo. The ability to quantify the local concentrations of these particles could be of great benefit for estimating local drug concentrations and developing new pharmacokinetic and pharmacodynamic paradigms to describe this new class of

  2. Positive synovial vascularity in patients with low disease activity indicates smouldering inflammation leading to joint damage in rheumatoid arthritis: time-integrated joint inflammation estimated by synovial vascularity in each finger joint.

    Science.gov (United States)

    Fukae, Jun; Isobe, Masato; Kitano, Akemi; Henmi, Mihoko; Sakamoto, Fumihiko; Narita, Akihiro; Ito, Takeya; Mitsuzaki, Akio; Shimizu, Masato; Tanimura, Kazuhide; Matsuhashi, Megumi; Kamishima, Tamotsu; Atsumi, Tatsuya; Koike, Takao

    2013-03-01

    To investigate the relationship between synovial vascularity and joint damage progression in each finger joint of patients with RA under low disease activity during treatment with biologic agents. We studied 310 MCP and 310 PIP joints of 31 patients with active RA who were administered adalimumab (ADA) or tocilizumab (TCZ). Patients were examined with clinical and laboratory assessments. Power Doppler sonography was performed at baseline and at weeks 8, 20 and 40. Synovial vascularity was evaluated according to quantitative measurement. Hand and foot radiography was performed at baseline and at week 50. Composite scores of the DAS with 28 joints and the Simplified Disease Activity Index (SDAI) were significantly decreased from baseline to week 8, being sustained at a low level by biologic agents during the observational period. MCP and PIP joints with positive synovial vascularity after week 8 showed more subsequent joint damage progression than joints without synovial vascularity throughout the follow-up. The changes in radiographic progression in these joints were independent of the sum of synovial vascularity from baseline to week 40 or the occasional occurrence of positive synovial vascularity. Smouldering inflammation reflected by positive synovial vascularity under low disease activity was linked to joint damage. The damage progressed irrespective of the severity of positive synovial vascularity. Even with a favourable overall therapeutic response, monitoring of synovial vascularity has the potential to provide useful joint information to tailor treatment strategies. Trial registration. University Hospital Medical Information Network Clinical Trials Registry; http://www.umin.ac.jp/ctr/; UMIN000004476.

  3. Factors modulating bioavailability of quercetin-related flavonoids and the consequences of their vascular function.

    Science.gov (United States)

    Terao, Junji

    2017-09-01

    Nowadays dietary flavonoids attract much attention in the prevention of chronic diseases. Epidemiological and intervention studies strongly suggest that flavonoid intake has beneficial effects on vascular health. It is unlikely that flavonoids act as direct antioxidants, although oxidative stress profoundly contributes to vascular impairment leading to cardiovascular diseases. Instead, flavonoids may exert their function by tuning the cellular redox state to an adaptive response or tolerable stress. However, the optimum intake of flavonoids from supplements or diet has not been clarified yet, because a number of exogenous and endogenous factors modulating their bioavailability affect their vascular function. This review will focus on the current knowledge of the bioavailability and vascular function of quercetin as a representative of antioxidative flavonoids. Current intervention studies imply that intake of quercetin-rich onion improves vascular health. Onion may be superior to quercetin supplement from the viewpoint of quercetin bioavailability, probably because the food matrix enhances the intestinal absorption of quercetin. α-Glucosylation increases its bioavailability by elevating the accessibility to the absorptive cells. Prenylation may enhance bioaccumulation at the target site by increasing the cellular uptake. However, these chemical modifications do not guarantee health benefits to the vascular system. Dietary quercetin is exclusively present as their conjugated form in the blood stream. Quercetin may exert its vascular function as an aglycone within macrophage cells after inflammation-induced deconjugation and as conjugated metabolites by targeting endothelial cells. The relationship between the bioavailability and bio-efficacy should be clarified, to evaluate the vascular function of a wide variety of dietary flavonoids. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Niacin Inhibits Vascular Inflammation via Downregulating Nuclear Transcription Factor-κB Signaling Pathway

    Science.gov (United States)

    Si, Yanhong; Zhang, Ying; Zhao, Jilong; Guo, Shoudong; Zhai, Lei; Yao, Shutong; Sang, Hui; Yang, Nana; Song, Guohua; Gu, Jue; Qin, Shucun

    2014-01-01

    The study aimed to investigate the effect of niacin on vascular inflammatory lesions in vivo and in vitro as well as its lipid-regulating mechanism. In vivo study revealed that niacin downregulated the levels of inflammatory factors (IL-6 and TNF-α) in plasma, suppressed protein expression of CD68 and NF-κB p65 in arterial wall, and attenuated oxidative stress in guinea pigs that have been fed high fat diet. In vitro study further confirmed that niacin decreased the secretion of IL-6 and TNF-α and inhibited NF-κB p65 and notch1 protein expression in oxLDL-stimulated HUVECs and THP-1 macrophages. Moreover, niacin attenuated oxLDL-induced apoptosis of HUVECs as well. In addition, niacin significantly lessened lipid deposition in arterial wall, increased HDL-C and apoA levels and decreased TG and non-HDL-C levels in plasma, and upregulated the mRNA amount of cholesterol 7α-hydroxylase A1 in liver of guinea pigs. These data suggest for the first time that niacin inhibits vascular inflammation in vivo and in vitro via downregulating NF-κB signaling pathway. Furthermore, niacin also modulates plasma lipid by upregulating the expression of factors involved in the process of reverse cholesterol transport. PMID:24991087

  5. Relationship of cigarette smoking with inflammation and subclinical vascular disease: the Multi-Ethnic Study of Atherosclerosis.

    Science.gov (United States)

    McEvoy, John W; Nasir, Khurram; DeFilippis, Andrew P; Lima, Joao A C; Bluemke, David A; Hundley, W Gregory; Barr, R Graham; Budoff, Matthew J; Szklo, Moyses; Navas-Acien, Ana; Polak, Joseph F; Blumenthal, Roger S; Post, Wendy S; Blaha, Michael J

    2015-04-01

    We sought to assess the impact of smoking status, cumulative pack-years, and time since cessation (the latter in former smokers only) on 3 important domains of cardiovascular disease: inflammation, vascular dynamics and function, and subclinical atherosclerosis. The Multi-Ethnic Study of Atherosclerosis (MESA) cohort enrolled 6814 adults without prior cardiovascular disease. Smoking variables were determined by self-report and confirmed with urinary cotinine. We examined cross-sectional associations between smoking parameters and (1) inflammatory biomarkers (high-sensitivity C-reactive protein [hsCRP], interleukin-6, and fibrinogen); (2) vascular dynamics and function (brachial flow-mediated dilation and carotid distensibility by ultrasound, as well as aortic distensibility by MRI); and (3) subclinical atherosclerosis (coronary artery calcification, carotid intima-media thickness, and ankle-brachial index). We identified 3218 never smokers, 2607 former smokers, and 971 current smokers. Mean age was 62 years and 47% were male. There was no consistent association between smoking and vascular distensibility or flow-mediated dilation outcomes. However, compared with never smokers, the adjusted association between current smoking and measures of either inflammation or subclinical atherosclerosis was consistently stronger than for former smoking (eg, odds ratio for hsCRP>2 mg/L of 1.7 [95% confidence interval, 1.5-2.1] versus 1.2 [1.1-1.4], odds ratio for coronary artery calcification>0 of 1.8 [1.5-2.1] versus 1.4 [1.2-1.6], respectively). Similar associations were seen for interleukin-6, fibrinogen, carotid intima-media thickness, and ankle-brachial index. A monotonic association was also found between higher pack-year quartiles and increasing inflammatory markers. Furthermore, current smokers with hsCRP>2 mg/L were more likely to have increased carotid intima-media thickness, abnormal ankle-brachial index, and coronary artery calcification>75th percentile for age, sex

  6. Effect of a rosmarinic acid supplemented hemodialysis fluid on inflammation of human vascular endothelial cells

    Directory of Open Access Journals (Sweden)

    W-J. Wang

    2017-10-01

    Full Text Available Chronic systemic inflammation and repetitive damage of vascular endothelia by incompatible dialysis system are probable causes of cardiovascular disease in patients on dialysis. The present study aimed to assess in vitro biocompatibility and anti-inflammatory effect of hemodialysis fluid supplemented with rosmarinic acid (RA using human umbilical vein endothelial cells (HUVEC. HUVECs (5×106 cells/mL were pre-exposed to 1 μg/mL of lipopolysaccharides (LPS and incubated with RA-supplemented hemodialysis fluid (HDF. Cytotoxicity was assessed qualitatively by morphologic assessment and quantitatively by MTT assay. Expressions of proinflammatory mediators were assessed using quantitative real-time PCR and production of NO was quantified. Phosphorylation of AKT and nuclear localization of nuclear factor kappa B (NF-κB were examined using western blotting. Exposure of HUVECs to RA-supplemented HDF had no influence on morphology and viability. Inhibition of proinflammatory mediator production in HUVECs by RA supplementation to HDF was significant in a dose-dependent manner. Exposure to RA-supplemented HDF resulted in a decrease in nitric oxide synthase expression and reduction of NO production in LPS-stimulated HUVECs. RA supplementation of HDF suppressed Akt activation in LPS-stimulated HUVECs. In addition, the level of cellular IκB was increased in parallel to a reduced nuclear translocation of NF-κB in LPS-induced endothelial cells. Our results suggest that RA-supplemented HDF is biocompatible and significantly suppressed inflammation induced in endothelial cells. In this respect, the use of HDF supplemented with RA could alleviate inflammation and improve long-term treatment of patients with renal failure on dialysis. Further clinical studies are required to confirm the effects.

  7. Effect of a rosmarinic acid supplemented hemodialysis fluid on inflammation of human vascular endothelial cells.

    Science.gov (United States)

    Wang, W-J; Cheng, M-H; Lin, J-H; Weng, C-S

    2017-10-19

    Chronic systemic inflammation and repetitive damage of vascular endothelia by incompatible dialysis system are probable causes of cardiovascular disease in patients on dialysis. The present study aimed to assess in vitro biocompatibility and anti-inflammatory effect of hemodialysis fluid supplemented with rosmarinic acid (RA) using human umbilical vein endothelial cells (HUVEC). HUVECs (5×106 cells/mL) were pre-exposed to 1 μg/mL of lipopolysaccharides (LPS) and incubated with RA-supplemented hemodialysis fluid (HDF). Cytotoxicity was assessed qualitatively by morphologic assessment and quantitatively by MTT assay. Expressions of proinflammatory mediators were assessed using quantitative real-time PCR and production of NO was quantified. Phosphorylation of AKT and nuclear localization of nuclear factor kappa B (NF-κB) were examined using western blotting. Exposure of HUVECs to RA-supplemented HDF had no influence on morphology and viability. Inhibition of proinflammatory mediator production in HUVECs by RA supplementation to HDF was significant in a dose-dependent manner. Exposure to RA-supplemented HDF resulted in a decrease in nitric oxide synthase expression and reduction of NO production in LPS-stimulated HUVECs. RA supplementation of HDF suppressed Akt activation in LPS-stimulated HUVECs. In addition, the level of cellular IκB was increased in parallel to a reduced nuclear translocation of NF-κB in LPS-induced endothelial cells. Our results suggest that RA-supplemented HDF is biocompatible and significantly suppressed inflammation induced in endothelial cells. In this respect, the use of HDF supplemented with RA could alleviate inflammation and improve long-term treatment of patients with renal failure on dialysis. Further clinical studies are required to confirm the effects.

  8. Vascular Burden and Cognitive Function in Late-Life Depression

    NARCIS (Netherlands)

    Zuidersma, Marij; Izaks, Gerbrand J.; Naarding, Paul; Comijs, Hannie C.; Oude Voshaar, Richard C.

    OBJECTIVE: To evaluate the relation of vascular risk factors, subclinical, and manifest vascular disease with four domains of cognitive functioning in a large sample of clinically depressed older persons. METHODS: A cross-sectional analysis was used, and depressed patients were recruited from

  9. Vascular Function and Structure in Veteran Athletes after Myocardial Infarction.

    NARCIS (Netherlands)

    Maessen, M.F.H.; Eijsvogels, T.M.H.; Hijmans-Kersten, B.T.P.; Grotens, A.; Schreuder, T.H.A.; Hopman, M.T.E.; Thijssen, D.H.J.

    2017-01-01

    PURPOSE: Although athletes demonstrate lower cardiovascular risk and superior vascular function compared with sedentary peers, they are not exempted from cardiac events (i.e., myocardial infarction [MI]). The presence of an MI is associated with increased cardiovascular risk and impaired vascular

  10. Structural and functional imaging for vascular targeted photodynamic therapy

    Science.gov (United States)

    Li, Buhong; Gu, Ying; Wilson, Brian C.

    2017-02-01

    Vascular targeted photodynamic therapy (V-PDT) has been widely used for the prevention or treatment of vascular-related diseases, such as localized prostate cancer, wet age-related macular degeneration, port wine stains, esophageal varices and bleeding gastrointestinal mucosal lesions. In this study, the fundamental mechanisms of vascular responses during and after V-PDT will be introduced. Based on the V-PDT treatment of blood vessels in dorsal skinfold window chamber model, the structural and functional imaging, which including white light microscopy, laser speckle imaging, singlet oxygen luminescence imaging, and fluorescence imaging for evaluating vascular damage will be presented, respectively. The results indicate that vessel constriction and blood flow dynamics could be considered as the crucial biomarkers for quantitative evaluation of vascular damage. In addition, future perspectives of non-invasive optical imaging for evaluating vascular damage of V-PDT will be discussed.

  11. Assessing vascular endothelial function using frequency and rank order statistics

    Science.gov (United States)

    Wu, Hsien-Tsai; Hsu, Po-Chun; Sun, Cheuk-Kwan; Liu, An-Bang; Lin, Zong-Lin; Tang, Chieh-Ju; Lo, Men-Tzung

    2013-08-01

    Using frequency and rank order statistics (FROS), this study analyzed the fluctuations in arterial waveform amplitudes recorded from an air pressure sensing system before and after reactive hyperemia (RH) induction by temporary blood flow occlusion to evaluate the vascular endothelial function of aged and diabetic subjects. The modified probability-weighted distance (PWD) calculated from the FROS was compared with the dilatation index (DI) to evaluate its validity and sensitivity in the assessment of vascular endothelial function. The results showed that the PWD can provide a quantitative determination of the structural changes in the arterial pressure signals associated with regulation of vascular tone and blood pressure by intact vascular endothelium after the application of occlusion stress. Our study suggests that the use of FROS is a reliable noninvasive approach to the assessment of vascular endothelial degeneration in aging and diabetes.

  12. Thalidomide Ameliorates Inflammation and Vascular Injury but Aggravates Tubular Damage in the Irradiated Mouse Kidney

    Energy Technology Data Exchange (ETDEWEB)

    Scharpfenecker, Marion, E-mail: m.scharpfenecker@nki.nl [Division of Biological Stress Response, The Netherlands Cancer Institute, Amsterdam (Netherlands); Floot, Ben [Division of Biological Stress Response, The Netherlands Cancer Institute, Amsterdam (Netherlands); Russell, Nicola S. [Division of Radiotherapy, The Netherlands Cancer Institute, Amsterdam (Netherlands); Coppes, Rob P. [Departments of Radiation Oncology and Cell Biology, University Medical Centre Groningen, University of Groningen, Groningen (Netherlands); Stewart, Fiona A. [Division of Biological Stress Response, The Netherlands Cancer Institute, Amsterdam (Netherlands)

    2014-07-01

    Purpose: The late side effects of kidney irradiation include vascular damage and fibrosis, which are promoted by an irradiation-induced inflammatory response. We therefore treated kidney-irradiated mice with the anti-inflammatory and angiogenesis-modulating drug thalidomide in an attempt to prevent the development of late normal tissue damage and radiation nephropathy in the mouse kidney. Methods and Materials: Kidneys of C57Bl/6 mice were irradiated with a single dose of 14 Gy. Starting from week 16 after irradiation, the mice were fed with thalidomide-containing chow (100 mg/kg body weight/day). Gene expression and kidney histology were analyzed at 40 weeks and blood samples at 10, 20, 30, and 40 weeks after irradiation. Results: Thalidomide improved the vascular structure and vessel perfusion after irradiation, associated with a normalization of pericyte coverage. The drug also reduced infiltration of inflammatory cells but could not suppress the development of fibrosis. Irradiation-induced changes in hematocrit and blood urea nitrogen levels were not rescued by thalidomide. Moreover, thalidomide worsened tubular damage after irradiation and also negatively affected basal tubular function. Conclusions: Thalidomide improved the inflammatory and vascular side effects of kidney irradiation but could not reverse tubular toxicity, which probably prevented preservation of kidney function.

  13. Effects of blueberries on inflammation, motor performance and cognitive function

    Science.gov (United States)

    Motor and cognitive function decrease with age, to include deficits in balance, coordination, gait, processing speed, executive function, memory, and spatial learning. These functional declines may be caused by long term increases in and susceptibility to oxidative stress and inflammation. Research ...

  14. In vitro assessment of mouse fetal abdominal aortic vascular function

    OpenAIRE

    Renshall, Lewis J.; Dilworth, Mark R.; Greenwood, Susan L.; Sibley, Colin P.; Wareing, Mark

    2014-01-01

    Fetal growth restriction (FGR) affects 3?8% of human pregnancies. Mouse models have provided important etiological data on FGR; they permit the assessment of treatment strategies on the physiological function of both mother and her developing offspring. Our study aimed to 1) develop a method to assess vascular function in fetal mice and 2) as a proof of principle ascertain whether a high dose of sildenafil citrate (SC; Viagra) administered to the pregnant dam affected fetal vascular reactivit...

  15. Modeling vascular inflammation and atherogenicity after inhalation of ambient levels of ozone: exploratory lessons from transcriptomics.

    Science.gov (United States)

    Tham, Andrea; Lullo, Dominic; Dalton, Sarah; Zeng, Siyang; van Koeverden, Ian; Arjomandi, Mehrdad

    2017-02-01

    Epidemiologic studies have linked inhalation of air pollutants such as ozone to cardiovascular mortality. Human exposure studies have shown that inhalation of ambient levels of ozone causes airway and systemic inflammation and an imbalance in sympathetic/parasympathetic tone. To explore molecular mechanisms through which ozone inhalation contributes to cardiovascular mortality, we compared transcriptomics data previously obtained from bronchoalveolar lavage (BAL) cells obtained from healthy subjects after inhalational exposure to ozone (200 ppb for 4 h) to those of various cell samples from 11 published studies of patients with atherosclerotic disease using the Nextbio genomic data platform. Overlapping gene ontologies that may be involved in the transition from pulmonary to systemic vascular inflammation after ozone inhalation were explored. Local and systemic enzymatic activity of an overlapping upregulated gene, matrix metalloproteinase-9 (MMP-9), was measured by zymography after ozone exposure. A set of differentially expressed genes involved in response to stimulus, stress, and wounding were in common between the ozone and most of the atherosclerosis studies. Many of these genes contribute to biological processes such as cholesterol metabolism dysfunction, increased monocyte adherence, endothelial cell lesions, and matrix remodeling, and to diseases such as heart failure, ischemia, and atherosclerotic occlusive disease. Inhalation of ozone increased MMP-9 enzymatic activity in both BAL fluid and serum. Comparison of transcriptomics between BAL cells after ozone exposure and various cell types from patients with atherosclerotic disease reveals commonly regulated processes and potential mechanisms by which ozone inhalation may contribute to progression of pre-existent atherosclerotic lesions.

  16. The Multifaceted Roles of PI3Kγ in Hypertension, Vascular Biology, and Inflammation

    Directory of Open Access Journals (Sweden)

    Marialuisa Perrotta

    2016-11-01

    Full Text Available PI3Kγ is a multifaceted protein, crucially involved in cardiovascular and immune systems. Several studies described the biological and physiological functions of this enzyme in the regulation of cardiovascular system, while others stressed its role in the modulation of immunity. Although PI3Kγ has been historically investigated for its role in leukocytes, the last decade of research also dedicated efforts to explore its functions in the cardiovascular system. In this review, we report an overview recapitulating how PI3Kγ signaling participates in the regulation of vascular functions involved in blood pressure regulation. Moreover, we also summarize the main functions of PI3Kγ in immune responses that could be potentially important in the interaction with the cardiovascular system. Considering that vascular and immune mechanisms are increasingly emerging as intertwining players in hypertension, PI3Kγ could be an intriguing pathway acting on both sides. The availability of specific inhibitors introduces a perspective of further translational research and clinical approaches that could be exploited in hypertension.

  17. The Multifaceted Roles of PI3Kγ in Hypertension, Vascular Biology, and Inflammation.

    Science.gov (United States)

    Perrotta, Marialuisa; Lembo, Giuseppe; Carnevale, Daniela

    2016-11-08

    PI3Kγ is a multifaceted protein, crucially involved in cardiovascular and immune systems. Several studies described the biological and physiological functions of this enzyme in the regulation of cardiovascular system, while others stressed its role in the modulation of immunity. Although PI3Kγ has been historically investigated for its role in leukocytes, the last decade of research also dedicated efforts to explore its functions in the cardiovascular system. In this review, we report an overview recapitulating how PI3Kγ signaling participates in the regulation of vascular functions involved in blood pressure regulation. Moreover, we also summarize the main functions of PI3Kγ in immune responses that could be potentially important in the interaction with the cardiovascular system. Considering that vascular and immune mechanisms are increasingly emerging as intertwining players in hypertension, PI3Kγ could be an intriguing pathway acting on both sides. The availability of specific inhibitors introduces a perspective of further translational research and clinical approaches that could be exploited in hypertension.

  18. Vascular Function and Structure in Veteran Athletes after Myocardial Infarction.

    Science.gov (United States)

    Maessen, Martijn F H; Eijsvogels, Thijs M H; Hijmans-Kersten, Bregina T P; Grotens, Ayla; Schreuder, Tim H A; Hopman, Maria T E; Thijssen, Dick H J

    2017-01-01

    Although athletes demonstrate lower cardiovascular risk and superior vascular function compared with sedentary peers, they are not exempted from cardiac events (i.e., myocardial infarction [MI]). The presence of an MI is associated with increased cardiovascular risk and impaired vascular function. We tested the hypothesis that lifelong exercise training in post-MI athletes, similar as in healthy controls, is associated with a superior peripheral vascular function and structure compared with a sedentary lifestyle in post-MI individuals. We included 18 veteran athletes (ATH) (>20 yr) and 18 sedentary controls (SED). To understand the effect of lifelong exercise training after MI, we included 20 veteran post-MI athletes (ATH + MI) and 19 sedentary post-MI controls (SED + MI). Participants underwent comprehensive assessment using vascular ultrasound (vascular stiffness, intima-media thickness, and endothelium (in)dependent mediated dilatation). Lifetime risk score was calculated for a 30-yr risk prediction of cardiovascular disease mortality of the participants. ATH demonstrated a lower vascular stiffness and smaller femoral intima-media thickness compared with SED. Vascular function and structure did not differ between ATH + MI and SED + MI. ATH (4.0% ± 5.1%) and ATH + MI (6.1% ± 3.7%) had a significantly better lifetime risk score compared with their sedentary peers (SED: 6.9% ± 3.7% and SED + MI: 9.3% ± 4.8%). ATH + MI had no secondary events versus two recurrent MI and six elective percutaneous coronary interventions within SED + MI (P < 0.05). Although veteran post-MI athletes did not have a superior peripheral vascular function and structure compared with their sedentary post-MI peers, benefits of lifelong exercise training in veteran post-MI athletes relate to a better cardiovascular risk profile and lower occurrence of secondary events.

  19. Function of histone deacetylase inhibitors in inflammation

    NARCIS (Netherlands)

    Grabiec, Aleksander M.; Tak, Paul P.; Reedquist, Kris A.

    2011-01-01

    Histone deacetylases (HDACs) display multi-faceted roles in coordinating the interaction of intracellular signaling pathways with chromatin remodeling and transcription factor function to finely specify gene alterations and maintenance of gene expression during cellular activation, proliferation,

  20. Luteolin protects against vascular inflammation in mice and TNF-alpha-induced monocyte adhesion to endothelial cells via suppressing IΚBα/NF-κB signaling pathway.

    Science.gov (United States)

    Jia, Zhenquan; Nallasamy, Palanisamy; Liu, Dongmin; Shah, Halley; Li, Jason Z; Chitrakar, Rojin; Si, Hongwei; McCormick, John; Zhu, Hong; Zhen, Wei; Li, Yunbo

    2015-03-01

    Vascular inflammation plays a significant role in the pathogenesis of atherosclerosis. Luteolin, a naturally occurring flavonoid present in many medicinal plants and some commonly consumed fruits and vegetables, has received wide attention for its potential to improve vascular function in vitro. However, its effect in vivo and the molecular mechanism of luteolin at physiological concentrations remain unclear. Here, we report that luteolin as low as 0.5 μM significantly inhibited tumor necrosis factor (TNF)-α-induced adhesion of monocytes to human EA.hy 926 endothelial cells, a key event in triggering vascular inflammation. Luteolin potently suppressed TNF-α-induced expression of the chemokine monocyte chemotactic protein-1 (MCP-1) and adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), key mediators involved in enhancing endothelial cell-monocyte interaction. Furthermore, luteolin inhibited TNF-α-induced nuclear factor (NF)-κB transcriptional activity, IκBα degradation, expression of IκB kinase β and subsequent NF-κB p65 nuclear translocation in endothelial cells, suggesting that luteolin can inhibit inflammation by suppressing NF-κB signaling. In an animal study, C57BL/6 mice were fed a diet containing 0% or 0.6% luteolin for 3 weeks, and luteolin supplementation greatly suppressed TNF-α-induced increase in circulating levels of MCP-1/JE, CXCL1/KC and sICAM-1 in C57BL/6 mice. Consistently, dietary intake of luteolin significantly reduced TNF-α-stimulated adhesion of monocytes to aortic endothelial cells ex vivo. Histology shows that luteolin treatment prevented the eruption of endothelial lining in the intima layer of the aorta and preserved elastin fibers' delicate organization as shown by Verhoeff-Van Gieson staining. Immunohistochemistry studies further show that luteolin treatment also reduced VCAM-1 and monocyte-derived F4/80-positive macrophages in the aorta of TNF-α-treated mice. In

  1. Systemic inflammation and lung function: A longitudinal analysis.

    Science.gov (United States)

    Hancox, Robert J; Gray, Andrew R; Sears, Malcolm R; Poulton, Richie

    2016-02-01

    Systemic inflammation is associated with impaired lung function in healthy adults as well as in patients with lung disease. The mechanism for this association is unknown and it is unclear if systemic inflammation leads to impaired lung function or if poor lung function leads to inflammation. We explored the temporal associations between blood C-reactive protein (CRP), fibrinogen, and white blood cells, and lung function in young adults. Spirometry, plethysmography, and diffusion capacity were measured in a population-based cohort at ages 32 and 38 years. High-sensitivity CRP, fibrinogen, and white blood cells were measured at the same ages. Higher levels of CRP and, to a lesser extent, fibrinogen were associated with lower lung volumes in cross-sectional analyses at both ages 32 and 38 years. Higher CRP and fibrinogen at age 32 were associated with higher FEV1 and FEV1/FVC at age 38, but not other measures of lung function. Lower lung volumes (total lung capacity, functional residual capacity, and residual volume) but not airflow obstruction (FEV1/FVC) at age 32 were associated with higher CRP at age 38. Associations between age 32 lung function and fibrinogen at follow-up were weaker, but consistent. There were no longitudinal associations between white blood cells and lung function. We found no evidence that systemic inflammation causes a decline in lung function. However, lower lung volumes were associated with higher CRP and fibrinogen at follow-up indicating that pulmonary restriction may be a risk factor for systemic inflammation. The mechanism for this association remains unclear. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Implications of Pericardial, Visceral and Subcutaneous Adipose Tissue on Vascular Inflammation Measured Using 18FDG-PET/CT.

    Directory of Open Access Journals (Sweden)

    Ho Cheol Hong

    Full Text Available Pericardial adipose tissue (PAT is associated with adverse cardiometabolic risk factors and cardiovascular disease (CVD. However, the relative implications of PAT, abdominal visceral and subcutaneous adipose tissue on vascular inflammation have not been explored.We compared the association of PAT, abdominal visceral fat area (VFA, and subcutaneous fat area (SFA with vascular inflammation, represented as the target-to-background ratio (TBR, the blood-normalized standardized uptake value measured using 18F-Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET in 93 men and women without diabetes or CVD. Age- and sex-adjusted correlation analysis showed that PAT, VFA, and SFA were positively associated with most cardiometabolic risk factors, including systolic blood pressure, LDL-cholesterol, triglycerides, glucose, insulin resistance and high sensitive C-reactive proteins (hsCRP, whereas they were negatively associated with HDL-cholesterol. In particular, the maximum TBR (maxTBR values were positively correlated with PAT and VFA (r = 0.48 and r = 0.45, respectively; both P <0.001, whereas SFA showed a relatively weak positive relationship with maxTBR level (r = 0.31, P = 0.003.This study demonstrated that both PAT and VFA are significantly and similarly associated with vascular inflammation and various cardiometabolic risk profiles.

  3. Magnetic ferroferric oxide nanoparticles induce vascular endothelial cell dysfunction and inflammation by disturbing autophagy

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Lu, E-mail: chaperones@163.com [College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou 450001 (China); Wang, XueQin; Miao, YiMing; Chen, ZhiQiang; Qiang, PengFei; Cui, LiuQing; Jing, Hongjuan [College of Bioengineering, Henan University of Technology, Lianhua Street, Zhengzhou 450001 (China); Guo, YuQi [Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 (China)

    2016-03-05

    Highlights: • B-Fe{sub 3}O{sub 4}NPs did not induce cell apoptosis or necrosis in HUVECs within 24 h. • B-Fe{sub 3}O{sub 4}NPs induced HUVEC dysfunction and inflammation. • B-Fe{sub 3}O{sub 4}NPs induced enhanced autophagic activity and blockade of autophagy flux. • Suppression of autophagy dysfunction attenuated B-Fe{sub 3}O{sub 4}NP-induced HUVEC dysfunction. - Abstract: Despite the considerable use of magnetic ferroferric oxide nanoparticles (Fe{sub 3}O{sub 4}NPs) worldwide, their safety is still an important topic of debate. In the present study, we detected the toxicity and biological behavior of bare-Fe{sub 3}O{sub 4}NPs (B-Fe{sub 3}O{sub 4}NPs) on human umbilical vascular endothelial cells (HUVECs). Our results showed that B-Fe{sub 3}O{sub 4}NPs did not induce cell death within 24 h even at concentrations up to 400 μg/ml. The level of nitric oxide (NO) and the activity of endothelial NO synthase (eNOS) were decreased after exposure to B-Fe{sub 3}O{sub 4}NPs, whereas the levels of proinflammatory cytokines were elevated. Importantly, B-Fe{sub 3}O{sub 4}NPs increased the accumulation of autophagosomes and LC3-II in HUVECs through both autophagy induction and the blockade of autophagy flux. The levels of Beclin 1 and VPS34, but not phosphorylated mTOR, were increased in the B-Fe{sub 3}O{sub 4}NP-treated HUVECs. Suppression of autophagy induction or stimulation of autophagy flux, at least partially, attenuated the B-Fe{sub 3}O{sub 4}NP-induced HUVEC dysfunction. Additionally, enhanced autophagic activity might be linked to the B-Fe{sub 3}O{sub 4}NP-induced production of proinflammatory cytokines. Taken together, these results demonstrated that B-Fe{sub 3}O{sub 4}NPs disturb the process of autophagy in HUVECs, and eventually lead to endothelial dysfunction and inflammation.

  4. Prunella vulgaris Suppresses HG-Induced Vascular Inflammation via Nrf2/HO-1/eNOS Activation

    Directory of Open Access Journals (Sweden)

    Ho Sub Lee

    2012-01-01

    Full Text Available Vascular inflammation is an important factor which can promote diabetic complications. In this study, the inhibitory effects of aqueous extract from Prunella vulgaris (APV on high glucose (HG-induced expression of cell adhesion molecules in human umbilical vein endothelial cells (HUVEC are reported. APV decreased HG-induced expression of intercellular adhesion molecule-1 (ICAM-1, vascular cell adhesion molecule-1 (VCAM-1, and E-selectin. APV also dose-dependently inhibited HG-induced adhesion of HL-60 monocytic cells. APV suppressed p65 NF-κB activation in HG-treated cells. APV significantly inhibited the formation of intracellular reactive oxygen species (ROS. HG-stimulated HUVEC secreted gelatinases, however, APV inhibited it. APV induced Akt phosphorylation as well as activation of heme oxygenase-1 (HO-1, eNOS, and nuclear factor E2-related factor 2 (Nrf2, which may protect vascular inflammation caused by HG. In conclusion, APV exerts anti-inflammatory effect via inhibition of ROS/NF-κB pathway by inducing HO-1 and eNOS expression mediated by Nrf2, thereby suggesting that Prunella vulgaris may be a possible therapeutic approach to the inhibition of diabetic vascular diseases.

  5. VASCULAR INFLAMMATION AND ABNORMAL AORTIC HISTOMORPHOMETRY IN PATIENTS FOLLOWING PULSATILE AND CONTINUOUS FLOW LEFT VENTRICULAR ASSIST DEVICE PLACEMENT

    Science.gov (United States)

    Lee, Mike; Akashi, Hirokazu; Kato, Tomoko S.; Takayama, Hiroo; Wu, Christina; Xu, Katherine; Collado, Elias; Weber, Matthew P.; Kennel, Peter J.; Brunjes, Danielle L; Ji, Ruiping; Naka, Yoshifumi; George, Isaac; Mancini, Donna; Farr, Maryjane; Schulze, P. Christian

    2017-01-01

    Objective Left ventricular assist devices are increasingly used in patients with advanced heart failure as both destination therapy and bridge-to-transplantation. We aimed to analyze histomorphometric, structural and inflammatory changes following pulsatile and continuous flow left ventricular assist device placement. Method Clinical and echocardiographic data were collected from medical records. Aortic wall diameter, cellularity and inflammation were assessed by immunohistochemistry on aortic tissue collected at left ventricular assist device placement and at explantation during heart transplantation. Expression of adhesion molecules was quantified by western blot. Results Decellularization of the aortic tunica media was observed in patients receiving continuous flow support. Both device types showed an increased inflammatory response following left ventricular assist device placement with variable T cell and macrophage accumulations and increased expression of vascular E-selectin, ICAM and VCAM in the aortic wall. Conclusion Left ventricular assist device implantation is associated with distinct vascular derangements with development of vascular inflammation. These changes are pronounced in patients on continuous flow left ventricular assist and associated with aortic media decellularization. These findings help to explain the progressive aortic root dilation and vascular dysfunction in patients following continuous flow device placement. PMID:26899764

  6. Protein Kinase C Inhibitors as Modulators of Vascular Function and Their Application in Vascular Disease

    Directory of Open Access Journals (Sweden)

    Raouf A. Khalil

    2013-03-01

    Full Text Available Blood pressure (BP is regulated by multiple neuronal, hormonal, renal and vascular control mechanisms. Changes in signaling mechanisms in the endothelium, vascular smooth muscle (VSM and extracellular matrix cause alterations in vascular tone and blood vessel remodeling and may lead to persistent increases in vascular resistance and hypertension (HTN. In VSM, activation of surface receptors by vasoconstrictor stimuli causes an increase in intracellular free Ca2+ concentration ([Ca2+]i, which forms a complex with calmodulin, activates myosin light chain (MLC kinase and leads to MLC phosphorylation, actin-myosin interaction and VSM contraction. Vasoconstrictor agonists could also increase the production of diacylglycerol which activates protein kinase C (PKC. PKC is a family of Ca2+-dependent and Ca2+-independent isozymes that have different distributions in various blood vessels, and undergo translocation from the cytosol to the plasma membrane, cytoskeleton or the nucleus during cell activation. In VSM, PKC translocation to the cell surface may trigger a cascade of biochemical events leading to activation of mitogen-activated protein kinase (MAPK and MAPK kinase (MEK, a pathway that ultimately increases the myofilament force sensitivity to [Ca2+]i, and enhances actin-myosin interaction and VSM contraction. PKC translocation to the nucleus may induce transactivation of various genes and promote VSM growth and proliferation. PKC could also affect endothelium-derived relaxing and contracting factors as well as matrix metalloproteinases (MMPs in the extracellular matrix further affecting vascular reactivity and remodeling. In addition to vasoactive factors, reactive oxygen species, inflammatory cytokines and other metabolic factors could affect PKC activity. Increased PKC expression and activity have been observed in vascular disease and in certain forms of experimental and human HTN. Targeting of vascular PKC using PKC inhibitors may function in

  7. Overexpression of circadian clock protein cryptochrome (CRY) 1 alleviates sleep deprivation-induced vascular inflammation in a mouse model.

    Science.gov (United States)

    Qin, Bing; Deng, Yunlong

    2015-01-01

    Disturbance of the circadian clock by sleep deprivation has been proposed to be involved in the regulation of inflammation. However, the underlying mechanism of circadian oscillator components in regulating the pro-inflammatory process during sleep deprivation remains poorly understood. Using a sleep deprivation mouse model, we showed here that sleep deprivation increased the expression of pro-inflammatory cytokines expression and decreased the expression of cryptochrome 1 (CRY1) in vascular endothelial cells. Furthermore, the adhesion molecules including intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and E-selectin were elevated in vascular endothelial cells and the monocytes binding to vascular endothelial cells were also increased by sleep deprivation. Interestingly, overexpression of CRY1 in a mouse model by adenovirus vector significantly inhibited the expression of inflammatory cytokines and adhesion molecules, and NF-κB signal pathway activation, as well as the binding of monocytes to vascular endothelial cells. Using a luciferase reporter assay, we found that CRY1 could repress the transcriptional activity of nuclear factor (NF)-κB in vitro. Subsequently, we demonstrated that overexpression of CRY1 inhibited the basal concentration of cyclic adenosine monophosphate (cAMP), leading to decreased protein kinase A activity, which resulted in decreased phosphorylation of p65. Taken together, these results suggested that the overexpression of CRY1 inhibited sleep deprivation-induced vascular inflammation that might be associated with NF-κB and cAMP/PKA pathways. Copyright © 2014 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  8. Simple advice on lifestyle habits and long-term changes in biomarkers of inflammation and vascular adhesion in healthy middle-aged men.

    Science.gov (United States)

    Sjögren, P; Cederholm, T; Heimbürger, M; Stenvinkel, P; Vedin, I; Palmblad, J; Hellenius, M-L

    2010-12-01

    Lifestyle habits, vascular function and inflammation are components in the development of cardiovascular disease (CVD). We investigated whether simple advice on dietary and exercise habits given (at a single time point) to hypercholesterolemic men affects circulating biomarkers of inflammation and vascular adhesion. In total, 157 men (age 46±5 years) with mild hypercholesterolemia were randomized to four intervention groups, diet (D, n=40), exercise (E, n=39), diet and exercise (DE, n=39) or controls (C, n=39) and serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1) and soluble E-selectin (sE-selectin) were quantified at baseline and after a 6-month intervention period. The intervention applied in this study, that is, simple advice on lifestyle changes given at a single time point, had a modest effect on inflammatory biomarkers and soluble vascular adhesion molecules. The most apparent alterations were found for individuals in group DE, who responded with significant reductions in sICAM-1, -28 (-41 to -14 μg/l) and sE-selectin, -3.6 (-6.9 to -0.3 μg/l) after 6 months. None of the groups had altered their concentrations of sVCAM-1, CRP or IL-6 significantly after the intervention. In all individuals combined, we found changes in apolipoprotein B (apoB) to predict alterations in sICAM-1 (β=0.21) and sE-selectin (β=0.26), independently of changes in inflammation and other adhesion molecules. These observations indicate that even small efforts to improve diet and physical activity can influence biomarkers of vascular function in individuals at increased risk for CVD. ApoB was identified as an important determinant of this improvement, which adds further support to the notion of apoB as a critical target in cardiovascular prevention.

  9. In vitro assessment of mouse fetal abdominal aortic vascular function.

    Science.gov (United States)

    Renshall, Lewis J; Dilworth, Mark R; Greenwood, Susan L; Sibley, Colin P; Wareing, Mark

    2014-09-15

    Fetal growth restriction (FGR) affects 3-8% of human pregnancies. Mouse models have provided important etiological data on FGR; they permit the assessment of treatment strategies on the physiological function of both mother and her developing offspring. Our study aimed to 1) develop a method to assess vascular function in fetal mice and 2) as a proof of principle ascertain whether a high dose of sildenafil citrate (SC; Viagra) administered to the pregnant dam affected fetal vascular reactivity. We developed a wire myography methodology for evaluation of fetal vascular function in vitro using the placenta-specific insulin-like growth factor II (Igf2) knockout mouse (P0; a model of FGR). Vascular function was determined in abdominal aortas isolated from P0 and wild-type (WT) fetuses at embryonic day (E) 18.5 of gestation. A subset of dams received SC 0.8 mg/ml via drinking water from E12.5; data were compared with water-only controls. Using wire myography, we found that fetal aortic rings exhibited significant agonist-induced contraction, and endothelium-dependent and endothelium-independent relaxation. Sex-specific alterations in reactivity were noted in both strains. Maternal treatment with SC significantly attenuated endothelium-dependent and endothelium-independent relaxation of fetal aortic rings. Mouse fetal abdominal aortas reproducibly respond to vasoactive agents. Study of these vessels in mouse genetic models of pregnancy complications may 1) help to delineate early signs of abnormal vascular reactivity and 2) inform whether treatments given to the mother during pregnancy may impact upon fetal vascular function. Copyright © 2014 the American Physiological Society.

  10. Effect of long-term treatment with melatonin on vascular markers of oxidative stress/inflammation and on the anticontractile activity of perivascular fat in aging mice.

    Science.gov (United States)

    Agabiti-Rosei, Claudia; Favero, Gaia; De Ciuceis, Carolina; Rossini, Claudia; Porteri, Enzo; Rodella, Luigi Fabrizio; Franceschetti, Lorenzo; Maria Sarkar, Anna; Agabiti-Rosei, Enrico; Rizzoni, Damiano; Rezzani, Rita

    2017-01-01

    Some reports have suggested that inflammation in perivascular adipose tissue (PVAT) may be implicated in vascular dysfunction by causing the disappearance of an anticontractile effect. The aim of this study was to investigate the effects of chronic melatonin treatment on the functional responses of the small mesenteric arteries and on the expression of markers of inflammation/oxidative stress in the aortas of senescence-accelerated prone mice (SAMP8), a model of age-related vascular dysfunction. We investigated seven SAMP8 and seven control senescence-accelerated resistant mice (SAMR1) treated for 10 months with melatonin, as well as equal numbers of age-matched untreated SAMP8 and SAMR1. The mesenteric small resistance arteries were dissected and mounted on a wire myograph, and the concentration-response to norepinephrine was evaluated in vessels with intact PVAT and after the removal of the PVAT. The expression of markers of oxidative stress, inflammation and aging in the aortas was evaluated by immunostaining. In addition, the adiponectin content and the expression of adiponectin receptor 1 were evaluated in the visceral adipose tissue. In untreated SAMP8 mice, we observed an overexpression of oxidative stress and inflammatory markers in the vasculature compared with the controls. No anticontractile effect of the PVAT was observed in untreated SAMP8 mice. Long-term treatment of SAMP8 mice with melatonin increased the expression of some markers of vasoprotection, decreased oxidative stress and inflammation and restored the anticontractile effect of the PVAT. Decreased expression of adiponectin and adiponectin receptor 1 was also observed in visceral fat of untreated SAMP8, whereas a significant increase was observed after melatonin treatment.

  11. Impact of AT2-receptor stimulation on vascular biology, kidney function, and blood pressure

    DEFF Research Database (Denmark)

    Danyel, L.A.; Schmerler, P.; Paulis, L.

    2013-01-01

    The angiotensin type 2 receptor (AT2R) and the receptor MAS are receptors within the renin-angiotensin system, which mediate tissue-protective actions such as anti-inflammation, antifibrosis, and antiapoptosis. In recent years, several programs have been launched in order to develop drugs that act...... angiotensin II) and with relevance for blood pressure (BP) regulation or hypertensive end-organ damage. These data will include studies on vasodilation/vasoconstriction in isolated resistance arteries ex vivo, studies on kidney function, studies on vascular remodeling, and studies that measured the net effect...... to attenuate hypertension-induced vascular remodeling and reduce arterial stiffening, which in more chronic settings and together with the natriuretic effect may result in modest lowering of BP. We conclude from these preclinical data that AT2R agonists are not suitable for antihypertensive monotherapy...

  12. Protein Kinase C as Regulator of Vascular Smooth Muscle Function and Potential Target in Vascular Disorders.

    Science.gov (United States)

    Ringvold, H C; Khalil, R A

    2017-01-01

    Vascular smooth muscle (VSM) plays an important role in maintaining vascular tone. In addition to Ca2+-dependent myosin light chain (MLC) phosphorylation, protein kinase C (PKC) is a major regulator of VSM function. PKC is a family of conventional Ca2+-dependent α, β, and γ, novel Ca2+-independent δ, ɛ, θ, and η, and atypical ξ, and ι/λ isoforms. Inactive PKC is mainly cytosolic, and upon activation it undergoes phosphorylation, maturation, and translocation to the surface membrane, the nucleus, endoplasmic reticulum, and other cell organelles; a process facilitated by scaffold proteins such as RACKs. Activated PKC phosphorylates different substrates including ion channels, pumps, and nuclear proteins. PKC also phosphorylates CPI-17 leading to inhibition of MLC phosphatase, increased MLC phosphorylation, and enhanced VSM contraction. PKC could also initiate a cascade of protein kinases leading to phosphorylation of the actin-binding proteins calponin and caldesmon, increased actin-myosin interaction, and VSM contraction. Increased PKC activity has been associated with vascular disorders including ischemia-reperfusion injury, coronary artery disease, hypertension, and diabetic vasculopathy. PKC inhibitors could test the role of PKC in different systems and could reduce PKC hyperactivity in vascular disorders. First-generation PKC inhibitors such as staurosporine and chelerythrine are not very specific. Isoform-specific PKC inhibitors such as ruboxistaurin have been tested in clinical trials. Target delivery of PKC pseudosubstrate inhibitory peptides and PKC siRNA may be useful in localized vascular disease. Further studies of PKC and its role in VSM should help design isoform-specific PKC modulators that are experimentally potent and clinically safe to target PKC in vascular disease. © 2017 Elsevier Inc. All rights reserved.

  13. Inflammation

    DEFF Research Database (Denmark)

    Holst-Hansen, Thomas

    Inflammation is an intricate response relying on the activation and response of both the innate immune system and the infected tissue to remove a threat. The pro-inflammatory NF-kappaB pathway has been studied extensively, among others because of its key role in regulation of inflammation. However...

  14. Diesel exhaust particulate induces pulmonary and systemic inflammation in rats without impairing endothelial function ex vivo or in vivo

    OpenAIRE

    Robertson Sarah; Gray Gillian A; Duffin Rodger; McLean Steven G; Shaw Catherine A; Hadoke Patrick WF; Newby David E; Miller Mark R

    2012-01-01

    Abstract Background Inhalation of diesel exhaust impairs vascular function in man, by a mechanism that has yet to be fully established. We hypothesised that pulmonary exposure to diesel exhaust particles (DEP) would cause endothelial dysfunction in rats as a consequence of pulmonary and systemic inflammation. Methods Wistar rats were exposed to DEP (0.5 mg) or saline vehicle by intratracheal instillation and hind-limb blood flow, blood pressure and heart rate were monitored in situ 6 or 24 h ...

  15. Methanol extract of Sorbus commixta cortex prevents vascular inflammation in rats with a high fructose-induced metabolic syndrome.

    Science.gov (United States)

    Kang, Dae Gill; Sohn, Eun Jin; Lee, An Sook; Kim, Jin Sook; Lee, Dae Ho; Lee, Ho Sub

    2007-01-01

    Feeding high fructose (Frc) to rats induces a moderate increase in blood pressure, which is associated with insulin resistance. The present study was designed to evaluate the effect of the methanol extract of Sorbus commixta cortex (MSC) on vascular inflammation in a rat model of the metabolic syndrome induced by a high Frc-diet. Male Sprague-Dawley rats were divided into 4 groups and treated for 7 weeks as follows: 1) control, 2) high Frc-diet group, 3) Frc/MSC1 group; high Frc-diet group treated with MSC (100 mg/kg/day), and 4) Frc/MSC2 group; high Frc-diet group treated with MSC (200 mg/kg/day). High Frc-induced decreases of the expression level of aortic endothelial nitric oxide synthase (ecNOS) while the production of cyclic GMP (cGMP) was restored by treatment with MSC. On the contrary, increases of the expression level of endothelin-1 (ET-1) in the aorta, the transcription factor, the cytokine related with vascular inflammation, and the adhesion molecules were suppressed by MSC treatment. Moreover, MSC treatment was shown to lessen the thickening noted in the aortic intima and media of the high Frc-diet group. Our findings suggest that MSC may have an anti-vascular inflammatory effect on rats with a high Frc-induced metabolic syndrome.

  16. Potential benefits of exercise on blood pressure and vascular function.

    Science.gov (United States)

    Pal, Sebely; Radavelli-Bagatini, Simone; Ho, Suleen

    2013-01-01

    Physical activity seems to enhance cardiovascular fitness during the course of the lifecycle, improve blood pressure, and is associated with decreased prevalence of hypertension and coronary heart disease. It may also delay or prevent age-related increases in arterial stiffness. It is unclear if specific exercise types (aerobic, resistance, or combination) have a better effect on blood pressure and vascular function. This review was written based on previous original articles, systematic reviews, and meta-analyses indexed on PubMed from years 1975 to 2012 to identify studies on different types of exercise and the associations or effects on blood pressure and vascular function. In summary, aerobic exercise (30 to 40 minutes of training at 60% to 85% of predicted maximal heart rate, most days of the week) appears to significantly improve blood pressure and reduce augmentation index. Resistance training (three to four sets of eight to 12 repetitions at 10 repetition maximum, 3 days a week) appears to significantly improve blood pressure, whereas combination exercise training (15 minutes of aerobic and 15 minutes of resistance, 5 days a week) is beneficial to vascular function, but at a lower scale. Aerobic exercise seems to better benefit blood pressure and vascular function. Copyright © 2013 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

  17. Diurnal Variation in Vascular and Metabolic Function in Diet-Induced Obesity

    Science.gov (United States)

    Prasai, Madhu J.; Mughal, Romana S.; Wheatcroft, Stephen B.; Kearney, Mark T.; Grant, Peter J.; Scott, Eleanor M.

    2013-01-01

    Circadian rhythms are integral to the normal functioning of numerous physiological processes. Evidence from human and mouse studies suggests that loss of rhythm occurs in obesity and cardiovascular disease and may be a neglected contributor to pathophysiology. Obesity has been shown to impair the circadian clock mechanism in liver and adipose tissue but its effect on cardiovascular tissues is unknown. We investigated the effect of diet-induced obesity in C57BL6J mice upon rhythmic transcription of clock genes and diurnal variation in vascular and metabolic systems. In obesity, clock gene function and physiological rhythms were preserved in the vasculature but clock gene transcription in metabolic tissues and rhythms of glucose tolerance and insulin sensitivity were blunted. The most pronounced attenuation of clock rhythm occurred in adipose tissue, where there was also impairment of clock-controlled master metabolic genes and both AMPK mRNA and protein. Across tissues, clock gene disruption was associated with local inflammation but diverged from impairment of insulin signaling. We conclude that vascular tissues are less sensitive to pathological disruption of diurnal rhythms during obesity than metabolic tissues and suggest that cellular disruption of clock gene rhythmicity may occur by mechanisms shared with inflammation but distinct from those leading to insulin resistance. PMID:23382450

  18. Small-Nucleic-Acid-Based Therapeutic Strategy Targeting the Transcription Factors Regulating the Vascular Inflammation, Remodeling and Fibrosis in Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Sung Won Youn

    2015-05-01

    Full Text Available Atherosclerosis arises when injury to the arterial wall induces an inflammatory cascade that is sustained by a complex network of cytokines, together with accumulation of lipids and fibrous material. Inflammatory cascades involve leukocyte adherence and chemotaxis, which are coordinated by the local secretion of adhesion molecules, chemotactic factors, and cytokines. Transcription factors are critical to the integration of the various steps of the cascade response to mediators of vascular injury, and are induced in a stimulus-dependent and cell-type-specific manner. Several small-nucleic-acid-based therapeutic strategies have recently been developed to target transcription factors: antisense oligodeoxynucleotides, RNA interference, microRNA, and decoy oligodeoxynucleotides. The aim of this review was to provide an overview of these particular targeted therapeutic strategies, toward regulation of the vascular inflammation, remodeling and fibrosis associated with atherosclerosis.

  19. You're Only as Old as Your Arteries: Translational Strategies for Preserving Vascular Endothelial Function with Aging

    Science.gov (United States)

    Kaplon, Rachelle E.; Gioscia-Ryan, Rachel A.; LaRocca, Thomas J.

    2014-01-01

    Endothelial dysfunction develops with age and increases the risk of age-associated vascular disorders. Nitric oxide insufficiency, oxidative stress, and chronic low-grade inflammation, induced by upregulation of adverse cellular signaling processes and imbalances in stress resistance pathways, mediate endothelial dysfunction with aging. Healthy lifestyle behaviors preserve endothelial function with aging by inhibiting these mechanisms, and novel nutraceutical compounds that favorably modulate these pathways hold promise as a complementary approach for preserving endothelial health. PMID:24985329

  20. A study of plaque vascularization and inflammation using quantitative contrast-enhanced US and PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Hjelmgren, Ola, E-mail: ola.hjelmgren@wlab.gu.se [Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Department of Molecular and Clinical Medicine, Clinical Physiology, Gothenburg (Sweden); Sahlgrenska University Hospital, Department of Clinical Physiology, Gothenburg (Sweden); Johansson, Lars, E-mail: lars.johansson@radiol.uu.se [Uppsala University, Department of Radiology, Uppsala (Sweden); Prahl, Ulrica, E-mail: ulrica-prahl-gullberg@wlab.gu.se [Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Department of Molecular and Clinical Medicine, Clinical Physiology, Gothenburg (Sweden); Schmidt, Caroline, E-mail: caroline.schmidt@wlab.gu.se [Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Department of Molecular and Clinical Medicine, Clinical Physiology, Gothenburg (Sweden); Fredén-Lindqvist, Johan, E-mail: johan.freden-lindqvist@vgregion.se [Sahlgrenska University Hospital, Department of Clinical Physiology, Gothenburg (Sweden); Bergström, Göran M.L., E-mail: goran.bergstrom@hjl.gu.se [Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Department of Molecular and Clinical Medicine, Clinical Physiology, Gothenburg (Sweden); Sahlgrenska University Hospital, Department of Clinical Physiology, Gothenburg (Sweden)

    2014-07-15

    Background: Contrast-enhanced ultrasound (CEUS) is an in vivo methodology to quantify carotid plaque vascularization. Increased metabolism in plaques, measured as FDG uptake in PET/CT examination, has been associated with markers of inflammation in histological samples. In this study, we tested the association between FDG uptake and vascularization measured by CEUS to assess whether CEUS can be used as an in vivo marker of plaque vulnerability. Methods: After informed consent, subjects aged >60 years with carotid plaque height exceeding 2.5 mm were recruited. CEUS was performed and analyzed using earlier described protocol and software, Contrast Quantification Program, which calculates the fraction of the plaque being contrast positive (CQP value). PET/CT examination was performed within 3 months of CEUS (median time 7 days). PET/CT images were acquired 90 min after FDG injection (2.7 MBq/kg). FDG uptake was measured as tissue background index (TBI), calculated using Spearman's rho as mean standard uptake value (SUV) of the plaque divided by mean SUV in the jugular vein (mean of 7 measuring points). Local ethics committee approved the study. Results: We recruited 13 subjects (5 women) with a mean age of 71 years, 6 had a history of stroke or TIA, 1 had a history of ipsilateral stroke. CQP values showed a significant, positive correlation with TBI of carotid plaques, r = 0.67, p < 0.02. Conclusions: Plaque vascularization measured by CEUS correlates positively with FDG uptake measured by PET/CT in humans. This indicates an association between vascularization and inflammation and/or hypoxia, supporting the use of CEUS as a non-invasive method to detect plaque vulnerability.

  1. Age Drives Distortion of Brain Metabolic, Vascular and Cognitive Functions, and the Gut Microbiome

    Directory of Open Access Journals (Sweden)

    Jared D. Hoffman

    2017-09-01

    Full Text Available Advancing age is the top risk factor for the development of neurodegenerative disorders, including Alzheimer’s disease (AD. However, the contribution of aging processes to AD etiology remains unclear. Emerging evidence shows that reduced brain metabolic and vascular functions occur decades before the onset of cognitive impairments, and these reductions are highly associated with low-grade, chronic inflammation developed in the brain over time. Interestingly, recent findings suggest that the gut microbiota may also play a critical role in modulating immune responses in the brain via the brain-gut axis. In this study, our goal was to identify associations between deleterious changes in brain metabolism, cerebral blood flow (CBF, gut microbiome and cognition in aging, and potential implications for AD development. We conducted our study with a group of young mice (5–6 months of age and compared those to old mice (18–20 months of age by utilizing metabolic profiling, neuroimaging, gut microbiome analysis, behavioral assessments and biochemical assays. We found that compared to young mice, old mice had significantly increased levels of numerous amino acids and fatty acids that are highly associated with inflammation and AD biomarkers. In the gut microbiome analyses, we found that old mice had increased Firmicutes/Bacteroidetes ratio and alpha diversity. We also found impaired blood-brain barrier (BBB function and reduced CBF as well as compromised learning and memory and increased anxiety, clinical symptoms often seen in AD patients, in old mice. Our study suggests that the aging process involves deleterious changes in brain metabolic, vascular and cognitive functions, and gut microbiome structure and diversity, all which may lead to inflammation and thus increase the risk for AD. Future studies conducting comprehensive and integrative characterization of brain aging, including crosstalk with peripheral systems and factors, will be necessary to

  2. Age Drives Distortion of Brain Metabolic, Vascular and Cognitive Functions, and the Gut Microbiome.

    Science.gov (United States)

    Hoffman, Jared D; Parikh, Ishita; Green, Stefan J; Chlipala, George; Mohney, Robert P; Keaton, Mignon; Bauer, Bjoern; Hartz, Anika M S; Lin, Ai-Ling

    2017-01-01

    Advancing age is the top risk factor for the development of neurodegenerative disorders, including Alzheimer's disease (AD). However, the contribution of aging processes to AD etiology remains unclear. Emerging evidence shows that reduced brain metabolic and vascular functions occur decades before the onset of cognitive impairments, and these reductions are highly associated with low-grade, chronic inflammation developed in the brain over time. Interestingly, recent findings suggest that the gut microbiota may also play a critical role in modulating immune responses in the brain via the brain-gut axis. In this study, our goal was to identify associations between deleterious changes in brain metabolism, cerebral blood flow (CBF), gut microbiome and cognition in aging, and potential implications for AD development. We conducted our study with a group of young mice (5-6 months of age) and compared those to old mice (18-20 months of age) by utilizing metabolic profiling, neuroimaging, gut microbiome analysis, behavioral assessments and biochemical assays. We found that compared to young mice, old mice had significantly increased levels of numerous amino acids and fatty acids that are highly associated with inflammation and AD biomarkers. In the gut microbiome analyses, we found that old mice had increased Firmicutes/Bacteroidetes ratio and alpha diversity. We also found impaired blood-brain barrier (BBB) function and reduced CBF as well as compromised learning and memory and increased anxiety, clinical symptoms often seen in AD patients, in old mice. Our study suggests that the aging process involves deleterious changes in brain metabolic, vascular and cognitive functions, and gut microbiome structure and diversity, all which may lead to inflammation and thus increase the risk for AD. Future studies conducting comprehensive and integrative characterization of brain aging, including crosstalk with peripheral systems and factors, will be necessary to define the

  3. Determinants of vascular function in patients with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Naka Katerina K

    2012-10-01

    Full Text Available Abstract Background Type 2 diabetes mellitus (T2DM is independently associated with an increased risk for cardiovascular diseases that is primarily due to the early development of advanced atherosclerotic vascular changes. The aim of our study was to investigate the predictors of vascular dysfunction in T2DM patients. Methods We studied 165 T2DM patients without known macrovascular or microvascular disease. Standard demographic (age, gender, cardiovascular risk factors, medications, clinical (body mass index, blood pressure and laboratory (glucose, glycated hemoglobin, lipids, renal function parameters were included in analyses. Brachial artery flow-mediated dilation (FMD, nitrate mediated dilation (NMD and Carotid-Femoral Pulse Wave Velocity (PWV were measured. Results Median age was 66 years and duration since T2DM diagnosis was 10 years, 70% were females and 79% hypertensives, while only 10% had a glycated hemoglobin Conclusions In T2DM patients, impairment of endothelium-dependent vasodilation was independently associated only with longer diabetes duration while no association with other established risk factors was found. Vascular smooth muscle dysfunction and increased arterial stiffness were more prominent in older T2DM patients with hypertension. Worse glycemic control was associated with impaired vascular smooth muscle function.

  4. Aerobic exercise training does not alter vascular structure and function in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Gelinas, Jinelle C; Lewis, Nia C; Harper, Megan I; Melzer, Bernie; Agar, Gloria; Rolf, J Douglass; Eves, Neil D

    2017-08-31

    What is the central question of this study? Chronic obstructive pulmonary disease (COPD) is associated with endothelial dysfunction, arterial stiffness and systemic inflammation, which are linked to increased cardiovascular disease risk. We asked whether periodized aerobic exercise training could improve vascular structure and function in patients with COPD. What is the main finding and its importance? Eight weeks of periodized aerobic training did not improve endothelial function, arterial stiffness or systemic inflammation in COPD, despite improvements in aerobic capacity, blood pressure and dyspnoea. Short-term training programmes may not be long enough to improve vascular-related cardiovascular risk in COPD. Chronic obstructive pulmonary disease (COPD) has been associated with endothelial dysfunction and arterial stiffening, which are predictive of future cardiovascular events. Although aerobic exercise improves vascular function in healthy individuals and those with chronic disease, it is unknown whether aerobic exercise can positively modify the vasculature in COPD. We examined the effects of 8 weeks of periodized aerobic training on vascular structure and function and inflammation in 24 patients with COPD (age, 69 ± 7 years; forced expiratory volume in 1 second as a percentage of predicted (FEV1 %pred), 68 ± 19%) and 20 matched control subjects (age, 64 ± 5 years; FEV1 %pred, 113 ± 16%) for comparison. Endothelial function was measured using brachial artery flow-mediated dilatation, whereas central and peripheral pulse wave velocity, carotid artery intima-media thickness, carotid compliance, distensibility and β-stiffness index were measured using applanation tonometry and ultrasound. Peak aerobic power (V̇O2 peak ) was measured using an incremental cycling test. Upper and lower body cycling training was performed three times per week for 8 weeks, and designed to optimize vascular adaptation by increasing and sustaining vascular shear

  5. The Soluble Epoxide Hydrolase Inhibitor AR9281 Decreases Blood Pressure, Ameliorates Renal Injury and Improves Vascular Function in Hypertension

    Directory of Open Access Journals (Sweden)

    Sean Shaw

    2009-12-01

    Full Text Available Soluble epoxide hydrolase inhibitors (sEHIs are demonstrating promise as potential pharmaceutical agents for the treatment of cardiovascular disease, diabetes, inflammation, and kidney disease. The present study determined the ability of a first-inclass sEHI, AR9281, to decrease blood pressure, improve vascular function, and decrease renal inflammation and injury in angiotensin hypertension. Rats were infused with angiotensin and AR9281 was given orally during the 14-day infusion period. Systolic blood pressure averaged 180 ± 5 mmHg in vehicle treated and AR9281 treatment significantly lowered blood pressure to 142 ± 7 mmHg in angiotensin hypertension. Histological analysis demonstrated decreased injury to the juxtamedullary glomeruli. Renal expression of inflammatory genes was increased in angiotensin hypertension and two weeks of AR9281 treatment decreased this index of renal inflammation. Vascular function in angiotensin hypertension was also improved by AR9281 treatment. Decreased afferent arteriolar and mesenteric resistance endothelial dependent dilator responses were ameliorated by AR9281 treatment of angiotensin hypertensive rats. These data demonstrate that the first-in-class sEHI, AR9281, lowers blood pressure, improves vascular function and reduces renal damage in angiotensin hypertension.

  6. Enzymatic regulation of functional vascular networks using gelatin hydrogels

    Science.gov (United States)

    Chuang, Chia-Hui; Lin, Ruei-Zeng; Tien, Han-Wen; Chu, Ya-Chun; Li, Yen-Cheng; Melero-Martin, Juan M.; Chen, Ying-Chieh

    2015-01-01

    To manufacture tissue engineering-based functional tissues, scaffold materials that can be sufficiently vascularized to mimic the functionality and complexity of native tissues are needed. Currently, vascular network bioengineering is largely carried out using natural hydrogels as embedding scaffolds, but most natural hydrogels have poor mechanical stability and durability, factors that critically limit their widespread use. In this study, we examined the suitability of gelatin-phenolic hydroxyl (gelatin-Ph) hydrogels that can be enzymatically crosslinked, allowing tuning of the storage modulus and the proteolytic degradation rate, for use as injectable hydrogels to support the human progenitor cell-based formation of a stable and mature vascular network. Porcine gelatin-Ph hydrogels were found to be cytocompatible with human blood-derived endothelial colony-forming cells and white adipose tissue-derived mesenchymal stem cells, resulting in >87% viability, and cell proliferation and spreading could be modulated by using hydrogels with different proteolytic degradability and stiffness. In addition, gelatin was extracted from mouse dermis and murine gelatin-Ph hydrogels were prepared. Importantly, implantation of human cell-laden porcine or murine gelatin-Ph hydrogels into immunodeficient mice resulted in the rapid formation of functional anastomoses between the bioengineered human vascular network and the mouse vasculature. Furthermore, the degree of enzymatic crosslinking of the gelatin-Ph hydrogels could be used to modulate cell behavior and the extent of vascular network formation in vivo. Our report details a technique for the synthesis of gelatin-Ph hydrogels from allogeneic or xenogeneic dermal skin and suggests that these hydrogels can be used for biomedical applications that require the formation of microvascular networks, including the development of complex engineered tissues. PMID:25749296

  7. Gender Differences in Bed Rest: Preliminary Analysis of Vascular Function

    Science.gov (United States)

    Platts, Steven H.; Stenger, Michael B.; Martin, David S.; Freeman-Perez, Sondra A.; Phillips, Tiffany; Ribeiro, L. Christine

    2008-01-01

    Orthostatic intolerance is a recognized consequence of spaceflight. Numerous studies have shown that women are more susceptible to orthostatic intolerance following spaceflight as well as bed rest, the most commonly used ground-based analog for spaceflight. One of the possible mechanisms proposed to account for this is a difference in vascular responsiveness between genders. We hypothesized that women and men would have differing vascular responses to 90 days of 6-degree head down tilt bed rest. Additionally, we hypothesized that vessels in the upper and lower body would respond differently, as has been shown in the animal literature. Thirteen subjects were placed in bedrest for 90 days (8 men, 5 women) at the Flight Analogs Unit, UTMB. Direct arterial and venous measurements were made with ultrasound to evaluate changes in vascular structure and function. Arterial function was assessed, in the arm and leg, during a reactive hyperemia protocol and during sublingual nitroglycerin administration to gauge the contributions of endothelial dependent and independent dilator function respectively. Venous function was assessed in dorsal hand and foot veins during the administration of pharmaceuticals to assess constrictor and dilator function. Both gender and day effects are seen in arterial dilator function to reactive hyperemia, but none are seen with nitroglycerin. There are also differences in the wall thickness in the arm vs the leg during bed rest, which return toward pre-bed rest levels by day 90. More subjects are required, especially females as there is not sufficient power to properly analyze venous function. Day 90 data are most underpowered.

  8. Polyphenol-containing azuki bean (Vigna angularis) seed coats attenuate vascular oxidative stress and inflammation in spontaneously hypertensive rats.

    Science.gov (United States)

    Mukai, Yuuka; Sato, Shin

    2011-01-01

    We investigated the effects of azuki bean (Vigna angularis) seed coats (ABSC), which contain polyphenols, on the vascular oxidative stress and inflammation associated with hypertension. Spontaneously hypertensive rats (SHR) and control normotensive Wistar-Kyoto (WKY) rats were divided into 2 groups each. One group was fed 0% ABSC; the other, a 1.0% ABSC-containing diet. Tail systolic blood pressure (SBP) was examined throughout ABSC treatment. At 8 weeks, vascular superoxide (O(2)(-)) production was measured by lucigenin-enhanced chemiluminescence. mRNA expressions of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, macrophage chemoattractant protein-1 (MCP-1) and its receptor C-C chemokine receptor 2 (CCR2) in the aorta were analyzed by reverse transcriptase-polymerase chain reaction. Protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were determined by western blotting. Polyphenol-containing ABSC suppressed the elevation of SBP throughout the treatment period. The NADPH-stimulated O(2)(-) level decreased significantly in the aorta of ABSC-treated SHR compared with the level of untreated SHR. The p47phox and Nox4 mRNA expression increased significantly in untreated SHR compared with that in WKY rats. Conversely, the level of p47phox mRNA was significantly lower in ABSC-treated SHR than in untreated SHR. The protein abundance of both iNOS and COX-2 was significantly decreased in the aorta of the ABSC-treated SHR compared with this abundance in untreated SHR. The MCP-1 and CCR2 mRNA expressions increased in untreated SHR, and these levels were significantly lower in ABSC-treated SHR. In conclusion, our results suggested that polyphenol-containing ABSC could attenuate vascular oxidative stress and inflammation during the progression of hypertension, and this may lead to an improvement in hypertension. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. A key role for the endothelium in NOD1 mediated vascular inflammation: comparison to TLR4 responses.

    Directory of Open Access Journals (Sweden)

    Timothy Gatheral

    Full Text Available Understanding the mechanisms by which pathogens induce vascular inflammation and dysfunction may reveal novel therapeutic targets in sepsis and related conditions. The intracellular receptor NOD1 recognises peptidoglycan which features in the cell wall of gram negative and some gram positive bacteria. NOD1 engagement generates an inflammatory response via activation of NFκB and MAPK pathways. We have previously shown that stimulation of NOD1 directly activates blood vessels and causes experimental shock in vivo. In this study we have used an ex vivo vessel-organ culture model to characterise the relative contribution of the endothelium in the response of blood vessels to NOD1 agonists. In addition we present the novel finding that NOD1 directly activates human blood vessels. Using human cultured cells we confirm that endothelial cells respond more avidly to NOD1 agonists than vascular smooth muscle cells. Accordingly we have sought to pharmacologically differentiate NOD1 and TLR4 mediated signalling pathways in human endothelial cells, focussing on TAK1, NFκB and p38 MAPK. In addition we profile novel inhibitors of RIP2 and NOD1 itself, which specifically inhibit NOD1 ligand induced inflammatory signalling in the vasculature. This paper is the first to demonstrate activation of whole human artery by NOD1 stimulation and the relative importance of the endothelium in the sensing of NOD1 ligands by vessels. This data supports the potential utility of NOD1 and RIP2 as therapeutic targets in human disease where vascular inflammation is a clinical feature, such as in sepsis and septic shock.

  10. Opposing functions of IKKβ during acute and chronic intestinal inflammation

    Science.gov (United States)

    Eckmann, Lars; Nebelsiek, Tim; Fingerle, Alexander A.; Dann, Sara M.; Mages, Jörg; Lang, Roland; Robine, Sylvie; Kagnoff, Martin F.; Schmid, Roland M.; Karin, Michael; Arkan, Melek C.; Greten, Florian R.

    2008-01-01

    NF-κB is a key transcriptional regulator of inflammatory responses, but also controls expression of prosurvival genes, whose products protect tissues from damage and may thus act indirectly in an antiinflammatory fashion. The variable importance of these two distinct NF-κB-controlled responses impacts the potential utility of NF-κB inhibition as a treatment strategy for intractable inflammatory conditions, such as inflammatory bowel disease. Here, we show in murine models that inhibition of IKKβ-dependent NF-κB activation exacerbates acute inflammation, but attenuates chronic inflammatory disease in the intestinal tract. Acute ulcerating inflammation is aggravated because of diminished NF-κB-mediated protection against epithelial cell apoptosis and delayed mucosal regeneration secondary to reduced NF-κB-dependent recruitment of inflammatory cells that secrete cytoprotective factors. In contrast, in IL-10-deficient mice, which serve as a model of chronic T cell-dependent colitis, ablation of IKKβ in the intestinal epithelium has no impact, yet IKKβ deficiency in myeloid cells attenuates inflammation and prolongs survival. These results highlight the striking context and tissue dependence of the proinflammatory and antiapoptotic functions of NF-κB. Our findings caution against the therapeutic use of IKKβ/NF-κB inhibitors in acute inflammatory settings dominated by cell loss and ulceration. PMID:18815378

  11. Opposing functions of IKKbeta during acute and chronic intestinal inflammation.

    Science.gov (United States)

    Eckmann, Lars; Nebelsiek, Tim; Fingerle, Alexander A; Dann, Sara M; Mages, Jörg; Lang, Roland; Robine, Sylvie; Kagnoff, Martin F; Schmid, Roland M; Karin, Michael; Arkan, Melek C; Greten, Florian R

    2008-09-30

    NF-kappaB is a key transcriptional regulator of inflammatory responses, but also controls expression of prosurvival genes, whose products protect tissues from damage and may thus act indirectly in an antiinflammatory fashion. The variable importance of these two distinct NF-kappaB-controlled responses impacts the potential utility of NF-kappaB inhibition as a treatment strategy for intractable inflammatory conditions, such as inflammatory bowel disease. Here, we show in murine models that inhibition of IKKbeta-dependent NF-kappaB activation exacerbates acute inflammation, but attenuates chronic inflammatory disease in the intestinal tract. Acute ulcerating inflammation is aggravated because of diminished NF-kappaB-mediated protection against epithelial cell apoptosis and delayed mucosal regeneration secondary to reduced NF-kappaB-dependent recruitment of inflammatory cells that secrete cytoprotective factors. In contrast, in IL-10-deficient mice, which serve as a model of chronic T cell-dependent colitis, ablation of IKKbeta in the intestinal epithelium has no impact, yet IKKbeta deficiency in myeloid cells attenuates inflammation and prolongs survival. These results highlight the striking context and tissue dependence of the proinflammatory and antiapoptotic functions of NF-kappaB. Our findings caution against the therapeutic use of IKKbeta/NF-kappaB inhibitors in acute inflammatory settings dominated by cell loss and ulceration.

  12. Bioprinting of a functional vascularized mouse thyroid gland construct.

    Science.gov (United States)

    Bulanova, Elena A; Koudan, Elizaveta V; Degosserie, Jonathan; Heymans, Charlotte; Pereira, Frederico DAS; Parfenov, Vladislav A; Sun, Yi; Wang, Qi; Akhmedova, Suraya A; Sviridova, Irina K; Sergeeva, Natalia S; Frank, Georgy A; Khesuani, Yusef D; Pierreux, Christophe E; Mironov, Vladimir A

    2017-08-18

    Bioprinting can be defined as additive biofabrication of three-dimensional (3D) tissues and organ constructs using tissue spheroids, capable of self-assembly, as building blocks. The thyroid gland, a relatively simple endocrine organ, is suitable for testing the proposed bioprinting technology. Here we report the bioprinting of a functional vascularized mouse thyroid gland construct from embryonic tissue spheroids as a proof of concept. Based on the self-assembly principle, we generated thyroid tissue starting from thyroid spheroids (TS) and allantoic spheroids (AS) as a source of thyrocytes and endothelial cells (EC), respectively. Inspired by mathematical modeling of spheroid fusion, we used an original 3D bioprinter to print TS in close association with AS within a collagen hydrogel. During the culture, closely placed embryonic tissue spheroids fused into a single integral construct, EC from AS invaded and vascularized TS, and epithelial cells from the TS progressively formed follicles. In this experimental setting, we observed formation of a capillary network around follicular cells, as observed during in utero thyroid development when thyroid epithelium controls the recruitment, invasion and expansion of EC around follicles. To prove that EC from AS are responsible for vascularization of the thyroid gland construct, we depleted endogenous EC from TS before bioprinting. EC from AS completely revascularized depleted thyroid tissue. The cultured bioprinted construct was functional as it could normalize blood thyroxine levels and body temperature after grafting under the kidney capsule of hypothyroid mice. Bioprinting of functional vascularized mouse thyroid gland construct represents a further advance in bioprinting technology, exploring the self-assembling properties of tissue spheroids.

  13. Genistein inhibits TNF-α-induced endothelial inflammation through the protein kinase pathway A and improves vascular inflammation in C57BL/6 mice

    OpenAIRE

    Jia, Zhenquan; Babu, Pon Velayutham Anandh; Si, Hongwei; Nallasamy, Palanisamy; Zhu, Hong; Zhen, Wei; Misra, Hara P.; Li, Yunbo; Liu, Dongmin

    2013-01-01

    Genistein, a soy isoflavone, has received wide attention for its potential to improve vascular function, but the mechanism of this effect is unclear. Here, we report that genistein at physiological concentrations (0.1 µM–5 µM) significantly inhibited TNF-α-induced adhesion of monocytes to human umbilical vein endothelial cells (HUVECs), a key event in the pathogenesis of atherosclerosis. Genistein also significantly suppressed TNF-α-induced production of adhesion molecules and chemokines such...

  14. Vascular and lung function related to ultrafine and fine particles exposure assessed by personal and indoor monitoring: a cross-sectional study

    DEFF Research Database (Denmark)

    Olsen, Yulia; Karottki, Dorina Gabriela; Jensen, Ditte Marie

    2014-01-01

    -related effects. Methods: Associations between vascular and lung function, inflammation markers and exposure in terms of particle number concentration (PNC; d = 10-300 nm) were studied in a cross-sectional design with personal and home indoor monitoring in the Western Copenhagen Area, Denmark. During 48-h, PNC...

  15. Association between Preoperative Vascular Function and Postoperative Arteriovenous Fistula Development.

    Science.gov (United States)

    Allon, Michael; Greene, Tom; Dember, Laura M; Vita, Joseph A; Cheung, Alfred K; Hamburg, Naomi M; Imrey, Peter B; Kaufman, James S; Robbin, Michelle L; Shiu, Yan-Ting; Terry, Christi M; Umphrey, Heidi R; Feldman, Harold I

    2016-12-01

    Arteriovenous fistula (AVF) maturation failure is the primary cause of dialysis vascular access dysfunction. To evaluate whether preoperative vascular functional properties predict postoperative AVF measurements, patients enrolled in the Hemodialysis Fistula Maturation Study underwent up to five preoperative vascular function tests (VFTs): flow-mediated dilation (FMD), nitroglycerin-mediated dilation (NMD), carotid-femoral pulse wave velocity, carotid-radial pulse wave velocity, and venous occlusion plethysmography. We used mixed effects multiple regression analyses to relate each preoperative VFT to ultrasound measurements of AVF blood flow rate and venous diameter at 1 day, 2 weeks, and 6 weeks after AVF placement. After controlling for AVF location, preoperative ultrasound measurements, and demographic factors (age, sex, race, and dialysis status), greater NMD associated with greater 6-week AVF blood flow rate and AVF diameter (per absolute 10% difference in NMD: change in blood flow rate =14.0%; 95% confidence interval [95% CI], 3.7% to 25.3%; Pfunctional arterial properties affect AVF development. Copyright © 2016 by the American Society of Nephrology.

  16. VEGFR-3 blocking deteriorates inflammation with impaired lymphatic function and different changes in lymphatic vessels in acute and chronic colitis.

    Science.gov (United States)

    Wang, Xiao-Lei; Zhao, Jing; Qin, Li; Cao, Jing-Li

    2016-01-01

    Recent studies show inflammation-associated lymphangiogenesis (IAL) induced by vascular endothelial growth factor receptor 3 (VEGFR-3) pathway has a close relationship with chronic intestinal inflammation, and antilymphatic signaling pathways may repress IAL. However, whether the biologic function of lymphatic vessel is the same in severe acute intestinal inflammation still remain unknown. C57BL/6 mice were administered with 5% of dextran sodium sulfate (DSS) in drinking water for 7 days to establish severe acute colitis (SAC) model. Chronic colitis (CC) model was established by three cycles of 2% DSS for 5 days following water for 5 days. Mice were treated with VEGFR-3 antibody once daily in SAC group, or once every 3 days in CC group. The colon inflammation, submucosal edema, lymphatic vessel (LV) density, LV size, lymph flow, cytokines and immune cells infiltration were detected. Both acute and chronic colitis resulted in a significant aggravation of colon inflammation in anti-VEGFR-3-treated mice, compared with PBS-treated colitis mice. Meanwhile, this was accompanied with decreased lymph drainage, increased submucosal edema, inflammatory cells infiltration and cytokines levels. In acute intestinal inflammation, significantly distorted and enlarged lymphatics were found but the LV number remained unchanged; not only significantly distorted and enlarged lymphatics but reduced LV number were found in chronic colitis. Blocking VEGFR-3 in acute and chronic colitis leads to deterioration of colon inflammation with impaired lymphatic function and different changes in LVs. In the therapy targeting VEGF-C/VEGFR-3 pathway for lymphangiogenesis, the phrase and severity of intestinal inflammation should be taken into account.

  17. Ocular surface inflammation impairs structure and function of meibomian gland.

    Science.gov (United States)

    Mizoguchi, Shin; Iwanishi, Hiroki; Arita, Reiko; Shirai, Kumi; Sumioka, Takayoshi; Kokado, Masahide; Jester, James V; Saika, Shizuya

    2017-10-01

    Dysfunction of the meibomian glands alters secreted meibum quantitatively and qualitatively that can lead to damage to the ocular surface epithelium. In response to an unstable tear film cause by meibomian gland dysfunction, ocular surface epithelium is damaged and expresses inflammatory cytokines leading to secondary ocular inflammation. In turn, inflammatory disorders of the palpebral conjunctiva and lid margin may affect the structure and function of meibomian gland. The disorders include allergic conjunctivitis, long-term usage of contact lenses, dermatological diseases that affect conjunctival homeostasis, Stevens-Johnson's syndrome or chemical burning of the ocular surface and lid margin. Copyright © 2017. Published by Elsevier Ltd.

  18. Diet induced mild hypercholesterolemia in pigs: local and systemic inflammation, effects on vascular injury - rescue by high-dose statin treatment.

    Directory of Open Access Journals (Sweden)

    Marco Busnelli

    Full Text Available OBJECTIVE: The aim of the present study was to comprehensively evaluate systemic and local inflammation as well as progression of vascular inflammation in normal and mechanically injured vessels in a large animal model of mild hypercholesterolemia. Our aim was also to test the effect of high-dose statin treatment on these processes. METHODS: Pigs were kept for 120 days on a standard diet (SD, n=7, high-cholesterol diet (HCD, n=7 or high-cholesterol diet with Atorvastatin starting after 50 days (STATIN, n=7. Left carotid artery balloon injury was conducted in all groups after 60 days of diet treatment. Biochemical analysis together with evaluation of blood and tissue markers of vascular injury and inflammation were performed in all groups at the end of experiment. RESULTS: HCD compared to SD induced systemic inflammation demonstrated by increased number of circulating monocytes and lymphocytes. HCD compared to SD induced also local inflammation demonstrated by adipocyte hypertrophy and infiltration of T-lymphocytes in abdominal white adipose tissue, activation of hepatic stellate cells with infiltration of T- and B-lymphocytes and macrophages in the liver and increased macrophage content in lung parenchyma. These changes were accompanied by increased Intima/Media thickness, stenosis, matrix deposition and activated T-cell infiltrates in injured but not in uninjured contralateral carotid artery as we previously reported. The treatment with high-dose statin attenuated all aspects of systemic and local inflammation as well as pathological changes in injured carotid artery. CONCLUSIONS: Diet related mild hypercholesterolemia induce systemic and local inflammation in the liver, lung and adipose tissue that coincide with enhanced inflammation of injured vessel but is without deleterious effect on uninjured vessels. High dose statin attenuated systemic and local inflammation and protected injured vessels. However, finding exact role of reduced systemic

  19. Thalidomide Ameliorates Inflammation and Vascular Injury but Aggravates Tubular Damage in the Irradiated Mouse Kidney

    NARCIS (Netherlands)

    Scharpfenecker, Marion; Floot, Ben; Russell, Nicola S.; Coppes, Rob P.; Stewart, Fiona A.

    2014-01-01

    Purpose: The late side effects of kidney irradiation include vascular damage and fibrosis, which are promoted by an irradiation-induced inflammatory response. We therefore treated kidney-irradiated mice with the anti-inflammatory and angiogenesis-modulating drug thalidomide in an attempt to prevent

  20. Sulforaphane inhibits restenosis by suppressing inflammation and the proliferation of vascular smooth muscle cells.

    Science.gov (United States)

    Kwon, Jin-Sook; Joung, Hosouk; Kim, Yong Sook; Shim, Young-Sun; Ahn, Youngkeun; Jeong, Myung Ho; Kee, Hae Jin

    2012-11-01

    Sulforaphane, a naturally occurring organosulfur compound in broccoli, has chemopreventive properties in cancer. However, the effects of sulforaphane in vascular diseases have not been examined. We therefore aimed to investigate the effects of sulforaphane on vascular smooth muscle cell (VSMC) proliferation and neointimal formation and the related mechanisms. The expression of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) was examined in VSMCs. The nuclear translocation of nuclear factor-κB (NF-κB) and GATA6 expression was examined in VSMCs and in a carotid artery injury model by Western blot and immunohistochemistry. We also investigated whether local delivery of sulforaphane affected neointimal formation. Sulforaphane inhibited the mRNA and protein expression of VCAM-1 induced by tumor necrosis factor (TNF)-α in VSMCs. Treatment of VSMCs with sulforaphane blocked TNF-α-induced IκBα degradation and NF-κB p65 and GATA6 expression. Furthermore, NF-κB p65 and GATA6 expression were reduced in sulforaphane-treated carotid injury sections. Notably, binding of GATA6 to the VCAM-1 promoter was dramatically reduced by sulforaphane. The MTT, BrdU incorporation, and in vitro scratch assays revealed that the proliferation and migration of VSMCs were reduced by sulforaphane. Furthermore, local administration of sulforaphane significantly reduced neointima formation 14 days after vascular injury in rats. Our results indicate that sulforaphane inhibits neointima formation via targeting of adhesion molecules through the suppression of NF-κB/GATA6. Furthermore, sulforaphane regulates migration and proliferation in VSMCs. Sulforaphane may be a potential therapeutic agent for preventing restenosis after vascular injury. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  1. Sulforaphane reduces vascular inflammation in mice and prevents TNF-α-induced monocyte adhesion to primary endothelial cells through interfering with the NF-κB pathway.

    Science.gov (United States)

    Nallasamy, Palanisamy; Si, Hongwei; Babu, Pon Velayutham Anandh; Pan, Dengke; Fu, Yu; Brooke, Elizabeth A S; Shah, Halley; Zhen, Wei; Zhu, Hong; Liu, Dongmin; Li, Yunbo; Jia, Zhenquan

    2014-08-01

    Sulforaphane, a naturally occurring isothiocyanate present in cruciferous vegetables, has received wide attention for its potential to improve vascular function in vitro. However, its effect in vivo and the molecular mechanism of sulforaphane at physiological concentrations remain unclear. Here, we report that a sulforaphane concentration as low as 0.5 μM significantly inhibited tumor necrosis factor-α (TNF-α)-induced adhesion of monocytes to human umbilical vein endothelial cells, a key event in the pathogenesis of atherosclerosis both in static and under flow conditions. Such physiological concentrations of sulforaphane also significantly suppressed TNF-α-induced production of monocyte chemotactic protein-1 and adhesion molecules including soluble vascular adhesion molecule-1 and soluble E-selectin, key mediators in the regulation of enhanced endothelial cell-monocyte interaction. Furthermore, sulforaphane inhibited TNF-α-induced nuclear factor (NF)-κB transcriptional activity, Inhibitor of NF-κB alpha (IκBα) degradation and subsequent NF-κB p65 nuclear translocation in endothelial cells, suggesting that sulforaphane can inhibit inflammation by suppressing NF-κB signaling. In an animal study, sulforaphane (300 ppm) in a mouse diet significantly abolished TNF-α-increased ex vivo monocyte adhesion and circulating adhesion molecules and chemokines in C57BL/6 mice. Histology showed that sulforaphane treatment significantly prevented the eruption of endothelial lining in the intima layer of the aorta and preserved elastin fibers' delicate organization, as shown by Verhoeff-van Gieson staining. Immunohistochemistry studies showed that sulforaphane treatment also reduced vascular adhesion molecule-1 and monocyte-derived F4/80-positive macrophages in the aorta of TNF-α-treated mice. In conclusion, sulforaphane at physiological concentrations protects against TNF-α-induced vascular endothelial inflammation, in both in vitro and in vivo models. This anti

  2. Doppler ultrasound findings correlate with tissue vascularity and inflammation in surgical pathology specimens from patients with small intestinal Crohn's disease.

    Science.gov (United States)

    Sasaki, Tomohiko; Kunisaki, Reiko; Kinoshita, Hiroto; Kimura, Hideaki; Kodera, Teruaki; Nozawa, Akinori; Hanzawa, Akiho; Shibata, Naomi; Yonezawa, Hiromi; Miyajima, Eiji; Morita, Satoshi; Fujii, Shoichi; Numata, Kazushi; Tanaka, Katsuaki; Tanaka, Masanori; Maeda, Shin

    2014-06-14

    Crohn's disease (CD) is routinely evaluated using clinical symptoms, laboratory variables, and the CD activity index (CDAI). However, clinical parameters are often nonspecific and do not precisely reflect the actual activity of CD small-intestinal lesions. The purposes of this prospective study were to compare color Doppler ultrasound (US) findings with histological findings from surgically resected specimens and confirm the hypothesis that color Doppler US can distinguish tissue inflammation and fibrosis. Among 1764 consecutive patients who underwent color Doppler US examinations, 10 patients with CD (12 small-intestinal CD lesions) who underwent US examinations before elective small-intestine resection were evaluated in the present study. Areas of thickened intestinal walls were evaluated in terms of blood flow using color Doppler US imaging. The blood flow was semiquantitatively classified as "hyper-flow" and "hypo-flow" according to the Limberg score. Resected lesions were macroscopically and histopathologically processed. Inflammatory cell infiltration, fibrosis and vascularity were evaluated by myeloperoxidase (granulocytes), CD163 (macrophages), CD79a (B cells), CD3 (T cells), Masson's trichrome (fibrosis), and factor VIII staining (vascular walls). All histopathological images were entered into virtual slide equipment and quantified using a quantitative microscopy integrated system (TissueMorph™). There were no significant differences in disease features or laboratory findings between "hypo-flow" lesions (n = 4) and "hyper-flow" lesions (n = 8). Histopathologically, "hyper-flow" lesions showed significantly greater bowel wall vascularity (factor VIII) (p = 0.047) and inflammatory cell infiltration, including CD163 macrophages (p = 0.008), CD3 T cells, and CD79a B cells (p = 0.043), than did "hypo-flow" lesions. There was no apparent association between the blood flow and CDAI. In this study, active CD lesions were macroscopically

  3. Monitoring asthma in childhood: lung function, bronchial responsiveness and inflammation.

    Science.gov (United States)

    Moeller, Alexander; Carlsen, Kai-Hakon; Sly, Peter D; Baraldi, Eugenio; Piacentini, Giorgio; Pavord, Ian; Lex, Christiane; Saglani, Sejal

    2015-06-01

    This review focuses on the methods available for measuring reversible airways obstruction, bronchial hyperresponsiveness (BHR) and inflammation as hallmarks of asthma, and their role in monitoring children with asthma. Persistent bronchial obstruction may occur in asymptomatic children and is considered a risk factor for severe asthma episodes and is associated with poor asthma outcome. Annual measurement of forced expiratory volume in 1 s using office based spirometry is considered useful. Other lung function measurements including the assessment of BHR may be reserved for children with possible exercise limitations, poor symptom perception and those not responding to their current treatment or with atypical asthma symptoms, and performed on a higher specialty level. To date, for most methods of measuring lung function there are no proper randomised controlled or large longitudinal studies available to establish their role in asthma management in children. Noninvasive biomarkers for monitoring inflammation in children are available, for example the measurement of exhaled nitric oxide fraction, and the assessment of induced sputum cytology or inflammatory mediators in the exhaled breath condensate. However, their role and usefulness in routine clinical practice to monitor and guide therapy remains unclear, and therefore, their use should be reserved for selected cases. Copyright ©ERS 2015.

  4. Monitoring asthma in childhood: lung function, bronchial responsiveness and inflammation

    Directory of Open Access Journals (Sweden)

    Alexander Moeller

    2015-06-01

    Full Text Available This review focuses on the methods available for measuring reversible airways obstruction, bronchial hyperresponsiveness (BHR and inflammation as hallmarks of asthma, and their role in monitoring children with asthma. Persistent bronchial obstruction may occur in asymptomatic children and is considered a risk factor for severe asthma episodes and is associated with poor asthma outcome. Annual measurement of forced expiratory volume in 1 s using office based spirometry is considered useful. Other lung function measurements including the assessment of BHR may be reserved for children with possible exercise limitations, poor symptom perception and those not responding to their current treatment or with atypical asthma symptoms, and performed on a higher specialty level. To date, for most methods of measuring lung function there are no proper randomised controlled or large longitudinal studies available to establish their role in asthma management in children. Noninvasive biomarkers for monitoring inflammation in children are available, for example the measurement of exhaled nitric oxide fraction, and the assessment of induced sputum cytology or inflammatory mediators in the exhaled breath condensate. However, their role and usefulness in routine clinical practice to monitor and guide therapy remains unclear, and therefore, their use should be reserved for selected cases.

  5. The role of inflammation in vascular insulin resistance with focus on IL-6

    DEFF Research Database (Denmark)

    Andersen, Kirsten; Pedersen, B.K.

    2008-01-01

    The present review focuses on the possible role of interleukin-(IL)-6 in vascular insulin resistance. The endothelium plays an important role in regulating the tone of the vasculature by releasing nitric oxide (NO) to the smooth muscles of the vessels, thereby regulating the distribution of blood...... flow to the various tissues in relation to their energy demand. A dysfunctioning endothelium has been associated with both initiation and progression of atherosclerotic cardiovascular (CV) disease and has been shown to predate the onset of hyperglycemia in the natural history of type 2 diabetes...... dysfunction and these cytokines. With regard to vascular insulin resistance, the available data point to a direct pathogenic role of TNF-alpha in mediating endothelial dysfunction, whereas with regard to IL-6 evidence is sparse and does not allow any firm conclusions Udgivelsesdato: 2008/9...

  6. Light-triggered in vivo activation of adhesive peptides regulates cell adhesion, inflammation and vascularization of biomaterials.

    Science.gov (United States)

    Lee, Ted T; García, José R; Paez, Julieta I; Singh, Ankur; Phelps, Edward A; Weis, Simone; Shafiq, Zahid; Shekaran, Asha; Del Campo, Aránzazu; García, Andrés J

    2015-03-01

    Materials engineered to elicit targeted cellular responses in regenerative medicine must display bioligands with precise spatial and temporal control. Although materials with temporally regulated presentation of bioadhesive ligands using external triggers, such as light and electric fields, have recently been realized for cells in culture, the impact of in vivo temporal ligand presentation on cell-material responses is unknown. Here, we present a general strategy to temporally and spatially control the in vivo presentation of bioligands using cell-adhesive peptides with a protecting group that can be easily removed via transdermal light exposure to render the peptide fully active. We demonstrate that non-invasive, transdermal time-regulated activation of cell-adhesive RGD peptide on implanted biomaterials regulates in vivo cell adhesion, inflammation, fibrous encapsulation, and vascularization of the material. This work shows that triggered in vivo presentation of bioligands can be harnessed to direct tissue reparative responses associated with implanted biomaterials.

  7. Comparative assessment of vascular function in autoimmune rheumatic diseases: considerations of prevention and treatment.

    Science.gov (United States)

    Soltész, Pál; Kerekes, György; Dér, Henriett; Szücs, Gabriella; Szántó, Sándor; Kiss, Emese; Bodolay, Edit; Zeher, Margit; Timár, Orsolya; Szodoray, Péter; Szegedi, Gyula; Szekanecz, Zoltán

    2011-05-01

    Numerous autoimmune-inflammatory rheumatic diseases have been associated with accelerated atherosclerosis or other types of vasculopathy leading to increased cardio- and cerebrovascular disease risk. Traditional risk factors, as well as the role of systemic inflammation including cytokines, chemokines, proteases, autoantibodies, adhesion receptors and others have been implicated in the development of these vascular pathologies. The characteristics of vasculopathies may significantly differ depending on the underlying disease. While classical accelerated atherosclerosis has been associated with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) or spondyloarthropathies (SpA), obliterative vasculopathy may rather be characteristic for systemic sclerosis (SSc) or mixed connective tissue disease (MCTD). Antiphospholipid antibodies have been implicated in vasculopathies underlying SLE, antiphospholipid syndrome (APS), RA and MCTD. There is also heterogeneity with respect to inflammatory risk factors. Cytokines, such as tumor necrosis factor-α (TNF-α) or interleukin 6 (IL-6) and immune complexes are primarily involved in arthritides, such as RA, SpA, as well as in SLE. On the other hand, autoantibodies including anti-oxLDL anti-cardiolipin and anti-β2GPI are rather involved in SLE- and APS-associated vasculopathies. Regarding the non-invasive assessment of vascular function, endothelial dysfunction, overt atherosclerosis and vascular stiffness may be indicated by brachial artery flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT) and aortic pulse-wave velocity (PWV), respectively. These abnormalities have been described in most inflammatory rheumatic diseases. While ccIMT and stiffness are relatively stable, FMD may be influenced by many confounding factors. In addition to traditional vasculoprotection, immunosuppressive agents including corticosteroids, traditional and biologic DMARDs may have significant vascular and metabolic

  8. Adiponectin, biomarkers of inflammation and changes in cardiac autonomic function

    DEFF Research Database (Denmark)

    Hansen, Christian Stevns; Vistisen, Dorte; Jørgensen, Marit Eika

    2017-01-01

    BACKGROUND: Biomarkers of inflammation and adiponectin are associated with cardiovascular autonomic neuropathy (CAN) in cross-sectional studies, but prospective data are scarce. This study aimed to assess the associations of biomarkers of subclinical inflammation and adiponectin with subsequent...

  9. Targeting inflammation to slow or delay functional decline: where are we?

    Science.gov (United States)

    Corsonello, Andrea; Garasto, Sabrina; Abbatecola, Angela Marie; Rose, Giuseppina; Passarino, Giuseppe; Mazzei, Bruno; Pranno, Luigi; Guffanti, Enrico Eugenio; Bustacchini, Silvia; Lattanzio, Fabrizia

    2010-10-01

    The role of inflammation in the pathophysiology of chronic age-related diseases is increasingly recognized, and inflammation could represent the common pathway linking diseases and disability. Thus, targeting inflammation could represent a useful strategy at preventing or delaying functional decline. In this paper we review recent evidence suggesting that selected drugs, such as statins, fibrates, angiotensin converting enzyme-inhibitors and angiotensin receptor blockers, and physical exercise may be able to contrast functional decline by blunting inflammation. Results from randomized trials investigating the effects of physical activity programs on inflammation and functional decline is still limited, and further investigations are warranted.

  10. Nebivolol for improving endothelial dysfunction, pulmonary vascular remodeling, and right heart function in pulmonary hypertension.

    Science.gov (United States)

    Perros, Frédéric; Ranchoux, Benoît; Izikki, Mohamed; Bentebbal, Sana; Happé, Chris; Antigny, Fabrice; Jourdon, Philippe; Dorfmüller, Peter; Lecerf, Florence; Fadel, Elie; Simonneau, Gerald; Humbert, Marc; Bogaard, Harm Jan; Eddahibi, Saadia

    2015-02-24

    Endothelial cell (EC) dysfunction plays a central role in the pathogenesis of pulmonary arterial hypertension (PAH), promoting vasoconstriction, smooth muscle proliferation, and inflammation. This study sought to test the hypothesis that nebivolol, a β1-antagonist and β2,3-agonist, may improve PAH and reverse the PAH-related phenotype of pulmonary ECs (P-EC). We compared the effects of nebivolol with metoprolol, a first-generation β1-selective β-blocker, on human cultured PAH and control P-EC proliferation, vasoactive and proinflammatory factor production, and crosstalk with PA smooth muscle cells. We assessed the effects of both β-blockers in precontracted PA rings. We also compared the effects of both β-blockers in experimental PAH. PAH P-ECs overexpressed the proinflammatory mediators interleukin-6 and monocyte chemoattractant protein-1, fibroblast growth factor-2, and the potent vasoconstrictive agent endothelin-1 as compared with control cells. This pathological phenotype was corrected by nebivolol but not metoprolol in a dose-dependent fashion. We confirmed that PAH P-EC proliferate more than control cells and stimulate more PA smooth muscle cell mitosis, a growth abnormality that was normalized by nebivolol but not by metoprolol. Nebivolol but not metoprolol induced endothelium-dependent and nitric oxide-dependent relaxation of PA. Nebivolol was more potent than metoprolol in improving cardiac function, pulmonary vascular remodeling, and inflammation of rats with monocrotaline-induced pulmonary hypertension. Nebivolol could be a promising option for the management of PAH, improving endothelial dysfunction, pulmonary vascular remodeling, and right heart function. Until clinical studies are undertaken, however, routine use of β-blockers in PAH cannot be recommended. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  11. Role of Renin-Angiotensin System and Oxidative Stress on Vascular Inflammation in Insulin Resistence Model

    OpenAIRE

    Renna, N. F.; Lembo, C.; Diez, E.; R. M. Miatello

    2013-01-01

    (1) is study aims to demonstrate the causal involvement of renin angiotensin system (RAS) and oxidative stress (OS) on vascular in��ammation in an experimental model of metabolic syndrome (MS) achieved by fructose administration to spontaneously hypertensive rats (FFHR) during 12 weeks. (2) Chronic treatment with candesartan (C) (10 mg/kg per day for the last 6 weeks) or 4OH-Tempol (T) (10−3 mmol/L in drinking water for the last 6 weeks) reversed the increment in metabolic variables and sys...

  12. Inflammation and vascular remodeling in the ventral hippocampus contributes to vulnerability to stress.

    Science.gov (United States)

    Pearson-Leary, J; Eacret, D; Chen, R; Takano, H; Nicholas, B; Bhatnagar, S

    2017-06-27

    During exposure to chronic stress, some individuals engage in active coping behaviors that promote resiliency to stress. Other individuals engage in passive coping that is associated with vulnerability to stress and with anxiety and depression. In an effort to identify novel molecular mechanisms that underlie vulnerability or resilience to stress, we used nonbiased analyses of microRNAs in the ventral hippocampus (vHPC) to identify those miRNAs differentially expressed in active (long-latency (LL)/resilient) or passive (short-latency (SL)/vulnerable) rats following chronic social defeat. In the vHPC of active coping rats, miR-455-3p level was increased, while miR-30e-3p level was increased in the vHPC of passive coping rats. Pathway analyses identified inflammatory and vascular remodeling pathways as enriched by genes targeted by these microRNAs. Utilizing several independent markers for blood vessels, inflammatory processes and neural activity in the vHPC, we found that SL/vulnerable rats exhibit increased neural activity, vascular remodeling and inflammatory processes that include both increased blood-brain barrier permeability and increased number of microglia in the vHPC relative to control and resilient rats. To test the relevance of these changes for the development of the vulnerable phenotype, we used pharmacological approaches to determine the contribution of inflammatory processes in mediating vulnerability and resiliency. Administration of the pro-inflammatory cytokine vascular endothelial growth factor-164 increased vulnerability to stress, while the non-steroidal anti-inflammatory drug meloxicam attenuated vulnerability. Collectively, these results show that vulnerability to stress is determined by a re-designed neurovascular unit characterized by increased neural activity, vascular remodeling and pro-inflammatory mechanisms in the vHPC. These results suggest that dampening inflammatory processes by administering anti-inflammatory agents reduces

  13. Recombinant lectin-like domain of thrombomodulin suppresses vascular inflammation by reducing leukocyte recruitment via interacting with Lewis Y on endothelial cells.

    Science.gov (United States)

    Lin, Wei-Ling; Chang, Chuan-Fa; Shi, Chung-Sheng; Shi, Guey-Yueh; Wu, Hua-Lin

    2013-10-01

    The N-terminal lectin-like domain (domain 1 [D1]) of thrombomodulin (TM) is known to have an anti-inflammatory function. We previously showed that recombinant TM domain 1 (rTMD1) interacts with a carbohydrate molecule, Lewis Y (Le(y)), which is found to be expressed on adhesion molecules and involved in cell adhesion. Here, we tested the effect of rTMD1/Le(y) interaction on leukocyte recruitment in inflammation. The expression of Le(y) on the surface of human umbilical vein endothelial cells was increased by tumor necrosis factor-α stimulation. Direct binding of rTMD1 to Le(y) on the cell surface was observed. rTMD1 inhibited Le(y)-mediated leukocyte adhesion on the Le(y)-immobilized flow chamber and activated endothelium under a shear flow. The following leukocyte transmigration to endothelium was also reduced by rTMD1 through binding Le(y). In vivo, treatment of rTMD1 reduced leukocyte recruitment to the inflammatory sites in carotid ligation injury and thioglycollate-induced peritonitis. rTMD1 administration in apolipoprotein E-deficient mice effectively suppressed atherosclerotic plaque formation and macrophage infiltration in atherosclerotic lesions. Increased Le(y) expression, as well as administered rTMD1, was observed in inflamed vessels. rTMD1 suppresses vascular inflammation by inhibiting leukocyte recruitment to endothelium through attenuating Le(y)-mediated adhesion and further protects against atherosclerosis progression. The present study provides a mechanism showing that rTMD1 can inhibit inflammation by binding to its carbohydrate ligand Le(y).

  14. HDL functionality and crystal-based sterile inflammation in atherosclerosis.

    Science.gov (United States)

    Eren, Esin; Ellidag, Hamit Yasar; Aydin, Ozgur; Yilmaz, Necat

    2015-01-15

    Change is inevitable. In early evolution, due to the limited availability of resources, the sole purpose of living organisms was to survive long enough to transmit their genes to the next generation. During their short lifetime, organisms used pathogen-associated and damage-associated molecular pattern pathways as an inflammatory response against pathogens (exogenous factors) and tissue damage (endogenous factors), respectively. Despite advances in human lifespan, it appears that an increasing number of diseases such as atherosclerosis are associated with inflammation. Excessive glucose, lipid and protein intake leads to the formation of endogenous crystals, i.e., cholesterol, which can induce a sterile inflammatory immune response that manifests as a vicious cycle. In this review, we evaluate the possible relationship between crystal-based sterile inflammatory response and HDL functionality. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Adipose Tissue Inflammation Induces B Cell Inflammation and Decreases B Cell Function in Aging

    Directory of Open Access Journals (Sweden)

    Daniela Frasca

    2017-08-01

    Full Text Available Aging is the greatest risk factor for developing chronic diseases. Inflamm-aging, the age-related increase in low-grade chronic inflammation, may be a common link in age-related diseases. This review summarizes recent published data on potential cellular and molecular mechanisms of the age-related increase in inflammation, and how these contribute to decreased humoral immune responses in aged mice and humans. Briefly, we cover how aging and related inflammation decrease antibody responses in mice and humans, and how obesity contributes to the mechanisms for aging through increased inflammation. We also report data in the literature showing adipose tissue infiltration with immune cells and how these cells are recruited and contribute to local and systemic inflammation. We show that several types of immune cells infiltrate the adipose tissue and these include macrophages, neutrophils, NK cells, innate lymphoid cells, eosinophils, T cells, B1, and B2 cells. Our main focus is how the adipose tissue affects immune responses, in particular B cell responses and antibody production. The role of leptin in generating inflammation and decreased B cell responses is also discussed. We report data published by us and by other groups showing that the adipose tissue generates pro-inflammatory B cell subsets which induce pro-inflammatory T cells, promote insulin resistance, and secrete pathogenic autoimmune antibodies.

  16. In vitro effects of waterpipe smoke condensate on endothelial cell function: a potential risk factor for vascular disease.

    Science.gov (United States)

    Rammah, Mayyasa; Dandachi, Farah; Salman, Rola; Shihadeh, Alan; El-Sabban, Marwan

    2013-05-23

    Despite its increasing popularity, little is known about the health effects of waterpipe smoking (WPS), particularly on the cardiovascular system. To investigate the role of WPS as a risk factor for vascular disease, we evaluated its effect on endothelial cell function, which is an early event in vascular disease pathogenesis. We assessed the changes in cell viability, ROS generation, inflammatory and vasodilatory markers and in vitro angiogenesis of human aortic endothelial cells in response to waterpipe smoke condensate exposure. Mainstream waterpipe smoke condensate (WSC) was generated using a standard laboratory machine protocol. Compared to control, WSC induced cell cycle arrest, apoptosis, and oxidative stress in human primary endothelial cells. In addition, we assayed for impaired endothelium-dependent vasodilation and induced inflammation by studying the effect of WPS on the content and activity of AMPK, eNOS proteins and NF-κB p65 ser536 phosphorylation, respectively. WSC inhibited AMPK/eNOS phosphorylation and induced phosphorylation of p65. Moreover, we evaluated endothelial cells repair mechanism related properties that include migration/invasion and in vitro tube formation upon treatment with WSC. WSC reduced the motility and inhibited angiogenic potential of HAEC cells. WPS induced endothelial cell dysfunction as evident by exerting oxidative stress, inflammation, and impaired endothelial vasodilatory function and repair mechanisms. All together these data provide evidence for the potential contribution of WPS to endothelial dysfunction and thus to vascular disease. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  17. Dietary fiber, kidney function, inflammation, and mortality risk.

    Science.gov (United States)

    Xu, Hong; Huang, Xiaoyan; Risérus, Ulf; Krishnamurthy, Vidya M; Cederholm, Tommy; Arnlöv, Johan; Lindholm, Bengt; Sjögren, Per; Carrero, Juan Jesús

    2014-12-05

    In the United States population, high dietary fiber intake has been associated with a lower risk of inflammation and mortality in individuals with kidney dysfunction. This study aimed to expand such findings to a Northern European population. Dietary fiber intake was calculated from 7-day dietary records in 1110 participants aged 70-71 years from the Uppsala Longitudinal Study of Adult Men (examinations performed during 1991-1995). Dietary fiber was adjusted for total energy intake by the residual method. Renal function was estimated from the concentration of serum cystatin C, and deaths were registered prospectively during a median follow-up of 10.0 years. Dietary fiber independently and directly associated with eGFR (adjusted difference, 2.6 ml/min per 1.73 m(2) per 10 g/d higher; 95% confidence interval [95% CI], 0.3 to 4.9). The odds of C-reactive protein >3 mg/L were lower (linear trend, P=0.002) with higher fiber quartiles. During follow-up, 300 participants died (incidence rate of 2.87 per 100 person-years at risk). Multiplicative interactions were observed between dietary fiber intake and kidney dysfunction in the prediction of mortality. Higher dietary fiber was associated with lower mortality in unadjusted analysis. These associations were stronger in participants with kidney dysfunction (eGFRdietary fiber was associated with better kidney function and lower inflammation in community-dwelling elderly men from Sweden. High dietary fiber was also associated with lower (cancer) mortality risk, especially in individuals with kidney dysfunction. Copyright © 2014 by the American Society of Nephrology.

  18. Soy isoflavones avert chronic inflammation-induced bone loss and vascular disease

    Directory of Open Access Journals (Sweden)

    Lightfoot Stan A

    2007-09-01

    Full Text Available Abstract Background Evidence from epidemiological, clinical and animal studies suggests a link may exist between low bone density and cardiovascular disease, with inflammatory mediators implicated in the pathophysiology of both conditions. This project examined whether supplementation with soy isoflavones (IF, shown to have anti-inflammatory properties, could prevent tissue expression of TNF-α and the development of skeletal pathology in an animal model of chronic inflammation. Methods Eight-week old, intact, female C57BL/6J mice were used. In Phase 1, a lipopolysaccharide (LPS-dose response study (0, 0.133, 1.33 and 13.3 μg/d was conducted to determine the LPS dose to use in Phase 2. The results indicated the 1.33 μg LPS/d dose produced the greatest decrease in lymphocytes and increase in neutrophils. Subsequently, in Phase 2, mice were randomly assigned to one of six groups (n = 12–13 per group: 0 or 1.33 μg LPS/d (placebo or LPS in combination with 0, 126 or 504 mg aglycone equivalents of soy IF/kg diet (Control, Low or High dose IF. Mice were fed IF beginning 2 wks prior to the 30-d LPS study period. Results At the end of the study, no differences were detected in final body weights or uterine weights. In terms of trabecular bone microarchitecture, μCT analyses of the distal femur metaphysis indicated that LPS significantly decreased trabecular bone volume (BV/TV and number (TbN, and increased separation (TbSp. Trabecular bone strength (i.e. total force and stiffness were also compromised in response to LPS. The High IF dose provided protection against these detrimental effects on microarchitecture, but not biomechanical properties. No alterations in trabecular thickness (TbTh, or cortical bone parameters were observed in response to the LPS or IF. Immunohistomchemical staining showed that tumor necrosis factor (TNF-α was up-regulated by LPS in the endothelium of small myocardial arteries and arterioles as well as the tibial

  19. Systemic inflammation and complications of”vascular" comorbidity in patients with COPD

    Directory of Open Access Journals (Sweden)

    A. S. Skotnikov

    2015-01-01

    Full Text Available In this article the authors examine the chronic obstructive pulmonary disease (COPD from the standpoint of comorbidity — in close connection with other common diseases of modern social comorbid patient. This article presents the known and suspected, confirmed and studied basic mechanisms of the pathogenesis of COPD and a number of systemic diseases. Typical pathological process, which the authors explain the stages of formation of comorbidity is a chronic systemic inflammation. On the pages of this paper reviewed the most famous today inflammatory markers and a causal connection with the increase of their concentration and worsening destabilization of these disease entities and clinical conditions such as coronary heart disease, hypertension, diabetes, obesity, atrial fibrillation, stroke, osteoporosis and malignant neoplasm.

  20. Arctigenin improves vascular tone and decreases inflammation in human saphenous vein.

    Science.gov (United States)

    Daci, Armond; Neziri, Burim; Krasniqi, Shaip; Cavolli, Raif; Alaj, Rame; Norata, Giuseppe Danilo; Beretta, Giangiacomo

    2017-09-05

    The goal of this study was to test the effects of bioactive phenylpropanoid dibenzylbutyrolactone lignan arctigenin (ATG) in vascular tone. Human bypass graft vessel, from a saphenous vein (SV), were set up in organ bath system and contracted with potassium chloride (KCl, 40mM). Two concentration-response curves of noradrenaline (NE) (10nM-100μM) separated with an incubation period of 30min without (Control) or with ATG (3-100μM) were established. Inhibitors of nitric oxide, prostaglandins, K+ related channels or calcium influx were used to delineate the molecular mechanisms beyond ATG effects. To investigate anti-inflammatory actions, SV were treated with 10μM or 100μM ATG and incubated for 18h in the absence or presence of both interleukin-1beta (IL-1β) and lipopolysaccharide (LPS) to mimic the physiological or inflamed tissue conditions. Proatherogenic and inflammatory mediators İnterleukine-1 beta (IL-1β), Monocyte Chemoattractant Proteine-1 (MCP-1), Tumor Necrosis Factor- α (TNF-α), İnterleukine-6 (IL-6), Prostaglandin E2 (PGE2) and İnterleukine-8 (IL-8) in the supernatant were measured. ATG significantly decreased vascular contractile response to NE. Moreover, it reduced contractions induced by KCl and cumulative addition of CaCl2. The mediators were significantly increased in inflammatory conditions compared to normal conditions, an effect which was inhibited by ATG (10 and 100µM). ATG reduces contractions in SV and decreases the production of proinflammatory-proatherogenic mediators, setting the stage for further evaluating the effect of ATG in cardiovascular diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Are markers of inflammation more strongly associated with risk for fatal than for nonfatal vascular events?

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    Naveed Sattar

    2009-06-01

    Full Text Available BACKGROUND: Circulating inflammatory markers may more strongly relate to risk of fatal versus nonfatal cardiovascular disease (CVD events, but robust prospective evidence is lacking. We tested whether interleukin (IL-6, C-reactive protein (CRP, and fibrinogen more strongly associate with fatal compared to nonfatal myocardial infarction (MI and stroke. METHODS AND FINDINGS: In the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER, baseline inflammatory markers in up to 5,680 men and women aged 70-82 y were related to risk for endpoints; nonfatal CVD (i.e., nonfatal MI and nonfatal stroke [n = 672], fatal CVD (n = 190, death from other CV causes (n = 38, and non-CVD mortality (n = 300, over 3.2-y follow-up. Elevations in baseline IL-6 levels were significantly (p = 0.0009; competing risks model analysis more strongly associated with fatal CVD (hazard ratio [HR] for 1 log unit increase in IL-6 1.75, 95% confidence interval [CI] 1.44-2.12 than with risk of nonfatal CVD (1.17, 95% CI 1.04-1.31, in analyses adjusted for treatment allocation. The findings were consistent in a fully adjusted model. These broad trends were similar for CRP and, to a lesser extent, for fibrinogen. The results were also similar in placebo and statin recipients (i.e., no interaction. The C-statistic for fatal CVD using traditional risk factors was significantly (+0.017; p<0.0001 improved by inclusion of IL-6 but not so for nonfatal CVD events (p = 0.20. CONCLUSIONS: In PROSPER, inflammatory markers, in particular IL-6 and CRP, are more strongly associated with risk of fatal vascular events than nonfatal vascular events. These novel observations may have important implications for better understanding aetiology of CVD mortality, and have potential clinical relevance.

  2. Longitudinal study of vascular structure and function during normal pregnancy.

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    Iacobaeus, C; Andolf, E; Thorsell, M; Bremme, K; Jörneskog, G; Östlund, E; Kahan, T

    2017-01-01

    To examine alterations in maternal vascular structure and function during normal pregnancy. We assessed brachial and central blood pressure, pulse-wave velocity and augmentation index (by pulse-wave analysis and applanation tonometry), common carotid artery structure (by ultrasonography) and endothelial function in the brachial artery (by postischemic hyperemia-induced flow-mediated vasodilatation by glyceryl trinitrate) and in the forearm skin microcirculation (by laser Doppler perfusion imaging during iontophoretic administration of acetylcholine and sodium nitroprusside) in 52 healthy nulliparous women at 14, 24 and 34 weeks' gestation, and at 9 months postpartum. During pregnancy, brachial and central systolic and diastolic blood pressures initially decreased but subsequently increased (all P pregnancy (P pregnancy (0.30 ± 0.18 in the non-pregnant state at 9 months postpartum and 0.51 ± 0.19, 0.61 ± 0.39 and 0.49 ± 0.30 in the first, second and third trimesters, respectively) (P reactivity to acetylcholine also increased (P pregnancy (5.88 ± 0.91 m/s in the non-pregnant state and 5.55 ± 0.67, 5.12 ± 0.66 and 5.62 ± 0.74 m/s in the first, second and third trimesters, respectively) (P pregnancy, the blood volume expansion necessary for sufficient fetal growth is accommodated by early and marked changes in the matvascular system. This seems to be dependent on normal adaptive endothelial and vascular function. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

  3. A comparison of the effect of alcohol and povidone-iodine mixture with alcohol after povidon-iodine in prevention of vascular access inflammation in patients undergoing hemodialysis

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    Bazzi A

    2014-11-01

    Full Text Available Background and Objective: The quality of hemodialysis can be promoted through reducing vascular access complications in these patients. One of the crucial roles of nurses in hemodialysis wards is reducing inflammation and infection of the vascular access. This study was conducted to compare the incidence of inflammation around the vascular access area in patients undergoing hemodialysis between two antiseptic methods of alcohol after povidone-iodine and the combination of alcohol and povidone-iodine. Materials and Method: This clinical trial was performed under the supervision of Mashhad University of Medical Sciences, Iran, after gaining ethical committee approval in 2014. In the present study, 100 participants were selected by convenience sampling method and randomly divided into three groups of combination of alcohol and povidone-iodine (n = 37, alcohol after using povidone-iodine (n = 32, and control group (n = 31. In the intervention groups 1 and 2, vascular access was disinfected using a combination of alcohol and povidone-iodine and alcohol after povidone-iodine, respectively. In the control group, vascular access was disinfected using the method of the related ward. Patients were fully observed for phlebitis occurrence for 12 hemodialysis sessions (1 month. Vascular access was controlled using the Iranian Nurses Association's phlebitis criteria. Data were analyzed using chi-square, ANOVA test, and Fisher's exact test in SPSS version 16. Results: The incidence rate of inflammation in the combination of alcohol and povidone-iodine, alcohol after povidone-iodine, and control groups, respectively, were 46%, 87.9%, and 100%. The incidence rate of inflammation was significantly lower in the combination of alcohol and povidone-iodine compared to the alcohol after povidone-iodine group (P < 0.001. However, no significant differences existed between the alcohol after povidone-iodine and control group. Conclusion: The combination of alcohol and

  4. Nitric oxide and reactive oxygen species in limb vascular function

    DEFF Research Database (Denmark)

    Gliemann, Lasse; Nyberg, Michael Permin; Hellsten, Ylva

    2014-01-01

    Abstract Nitric oxide (NO) is known to be one of the most important regulatory compounds within the cardiovascular system where it is central for functions such as regulation of blood pressure, blood flow and vascular growth. The bioavailability of NO is determined by a balance between, on one hand...... and xanthine oxidase and the degree of ROS removal through the antioxidant defense system. The development of cardiovascular disease has been proposed to be closely related to a reduced bioavailability of NO in parallel with an increased presence of ROS. Excessive levels of ROS not only lower....... Regular physical activity is therefore likely to be a highly useful tool in the treatment of cardiovascular disease. Future studies should focus on which form of exercise that may be most optimal for enhancing NO bioavailability and improving cardiovascular health....

  5. The VEGF-C/VEGFR3 signaling pathway contributes to resolving chronic skin inflammation by activating lymphatic vessel function.

    Science.gov (United States)

    Hagura, Asami; Asai, Jun; Maruyama, Kazuichi; Takenaka, Hideya; Kinoshita, Shigeru; Katoh, Norito

    2014-02-01

    The functions of lymphatic vessels are to drain the protein-rich lymph from the extracellular space, to maintain normal tissue pressure, and to mediate the immune response, particularly in inflammatory conditions. To evaluate the function of the vascular endothelial growth factor (VEGF)-C/VEGF receptor (VEGFR)-3 signaling pathway in chronic skin inflammation. We used adenovirus-mediated VEGF-C or VEGFR3-immunoglobulin (Ig) production and investigated the effects of VEGF-C/VEGFR3 signaling on the resolution of inflammation using the experimental chronic contact hypersensitivity (CHS) reaction mouse model. VEGF-C gene transfer promoted significant reduction of ear swelling and ear weight in CHS reaction-induced skin inflammation. Although, there was no significant difference in the number of lymphatic vessels, the number of infiltrating CD11b-positive inflammatory cells was significantly reduced in the VEGF-C group, which suggested that VEGF-C upregulated the drainage of interstitial fluid and inflammatory cells via lymphatic vessels. Furthermore, blockade of VEGFR3 expression resulted in a significant delay in the recovery from CHS reaction-induced skin inflammation. Lymphatic vessel size was enlarged and a significant increase of infiltrating CD11b inflammatory cells was observed in mice with VEGFR3-Ig gene transfer compared to control mice. These results suggested that blockade of VEGFR3 inhibited the drainage function of the lymphatic system. This study provides evidence that VEGF-C/VEGFR3 signaling plays an important role in the resolution of skin inflammation; the regulation of lymphatic function may have a great therapeutic potential in inflammatory skin diseases. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  6. Vascular function and mortality in haemodialysis patients: a pilot study.

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    Dalton, Brad S; Fassett, Robert G; Geraghty, Dominic P; De Ryke, Rex; Coombes, Jeff S

    2011-10-01

    Haemodialysis patients often have impaired vascular function that can contribute to mortality. Endothelial-dependent and -independent vascular function can be assessed using the brachial artery reactivity (BAR) technique that measures flow-mediated dilatation (FMD) and the response to glyceryl trinitrate (GTN), respectively. The aim of this pilot study was to determine whether BAR measurements in haemodialysis patients were associated with mortality. Brachial artery responses to FMD and administration of GTN were assessed in consecutive haemodialysis patients. Patients were then followed up to 18 months after BAR measurements. Seventeen patients were included in the study. After 18 months of follow-up, patients were divided into two groups: survived (n=12) and deceased (n=5). Patients who survived had a significantly greater median percentage vasodilatation to GTN than those who died (19.1% vs 8.8%; P=0.04); and a significantly greater median area under the diameter change-time curve (318 vs 146 mm/s; P=0.03). However, there were no significant differences between survivors and deceased in median percentage vasodilation to FMD (6.0% vs 4.3%; P=0.21), time to peak dilation (45 vs 40s; P=0.66) or area under the diameter change-time curve (35.5 vs 20 mm/s; P=0.29). In this pilot study in a small group of haemodialysis patients, endothelial-independent vasodilatory response to GTN was associated with mortality and was of better prognostic value than the endothelial-dependent response to FMD. This finding needs to be investigated in a larger cohort. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  7. MicroRNA-147b regulates vascular endothelial barrier function by targeting ADAM15 expression.

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    Victor Chatterjee

    Full Text Available A disintegrin and metalloproteinase15 (ADAM15 has been shown to be upregulated and mediate endothelial hyperpermeability during inflammation and sepsis. This molecule contains multiple functional domains with the ability to modulate diverse cellular processes including cell adhesion, extracellular matrix degradation, and ectodomain shedding of transmembrane proteins. These characteristics make ADAM15 an attractive therapeutic target in various diseases. The lack of pharmacological inhibitors specific to ADAM15 prompted our efforts to identify biological or molecular tools to alter its expression for further studying its function and therapeutic implications. The goal of this study was to determine if ADAM15-targeting microRNAs altered ADAM15-induced endothelial barrier dysfunction during septic challenge by bacterial lipopolysaccharide (LPS. An in silico analysis followed by luciferase reporter assay in human vascular endothelial cells identified miR-147b with the ability to target the 3' UTR of ADAM15. Transfection with a miR-147b mimic led to decreased total, as well as cell surface expression of ADAM15 in endothelial cells, while miR-147b antagomir produced an opposite effect. Functionally, LPS-induced endothelial barrier dysfunction, evidenced by a reduction in transendothelial electric resistance and increase in albumin flux across endothelial monolayers, was attenuated in cells treated with miR-147b mimics. In contrast, miR-147b antagomir exerted a permeability-increasing effect in vascular endothelial cells similar to that caused by LPS. Taken together, these data suggest the potential role of miR147b in regulating endothelial barrier function by targeting ADAM15 expression.

  8. Garlic and Onion Attenuates Vascular Inflammation and Oxidative Stress in Fructose-Fed Rats

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    Marcela Alejandra Vazquez-Prieto

    2011-01-01

    Full Text Available This study evaluates the antioxidant and the anti-inflammatory properties of garlic (G and onion (O in fructose-fed rats (FFR. Thirty-day-old male Wistar rats were assigned to control (C, F (10% fructose in drinking water, F+T (tempol 1 mM as control antioxidant, F+G, and F+O. Aqueous G and O extracts were administered orally in doses of 150 and 400 mg/kg/d respectively, and along with tempol, were given during the last 8 weeks of a 14-week period. At the end of the study, FFR had developed insulin resistance, aortic NADPH oxidase activity, increased SBP, plasma TBARS and vascular cell adhesion molecule-1 (VCAM-1 expression in mesenteric arteries, and a decrease in heart endothelial nitric oxide synthase (eNOS. Garlic and onion administration to F rats reduced oxidative stress, increased eNOS activity, and also attenuated VCAM-1 expression. These results provide new evidence showing the anti-inflammatory and antioxidant effect of these vegetables.

  9. Implication of Free Fatty Acids in Thrombin Generation and Fibrinolysis in Vascular Inflammation in Zucker Rats and Evolution with Aging

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    Jérémy Lagrange

    2017-11-01

    Full Text Available Background: The metabolic syndrome (MetS and aging are associated with modifications in blood coagulation factors, vascular inflammation, and increased risk of thrombosis.Objectives: Our aim was to determine concomitant changes in thrombin generation in the blood compartment and at the surface of vascular smooth muscle cells (VSMCs and its interplay with adipokines, free fatty acids (FFA, and metalloproteinases (MMPs in obese Zucker rats that share features of the human MetS.Methods: Obese and age-matched lean Zucker rats were compared at 25 and 80 weeks of age. Thrombin generation was assessed by calibrated automated thrombography (CAT.Results: Endogenous thrombin potential (ETP was increased in obese rats independent of platelets and age. Clot half-lysis time was delayed with obesity and age. Interleukin (IL-1β and IL-13 were increased with obesity and age respectively. Addition of exogenous fibrinogen, leptin, linoleic, or palmitic acid increased thrombin generation in plasma whereas adiponectin had an opposite effect. ETP was increased at the surface of VSMCs from obese rats and addition of exogenous palmitic acid further enhanced ETP values. Gelatinase activity was increased in aorta at both ages in obese rats and MMP-2 activity was increased in VSMCs from obese rats.Conclusions: Our study demonstrated in MetS an early prothrombotic phenotype of the blood compartment reinforced by procoagulant properties of dedifferentiated and inflammatory VSMCs. Mechanisms involved (1 increased fibrinogen and impaired fibrinolysis and (2 increased saturated fatty acids responsible for additive procoagulant effects. Whether specifically targeting this hypercoagulability using direct thrombin inhibitors would improve outcome in MetS is worth investigating.

  10. Neonates with reduced neonatal lung function have systemic low-grade inflammation

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    Chawes, Bo L.K.; Stokholm, Jakob; Bønnelykke, Klaus

    2015-01-01

    Background: Children and adults with asthma and impaired lung function have been reported to have low-grade systemic inflammation, but it is unknown whether this inflammation starts before symptoms and in particular whether low-grade inflammation is present in asymptomatic neonates with reduced...... lung function. ObjectiveWe sought to investigate the possible association between neonatal lung function and biomarkers of systemic inflammation.  Methods: Plasma levels of high-sensitivity C-reactive protein (hs-CRP), IL-1β, IL-6, TNF-α, and CXCL8 (IL-8) were measured at age 6 months in 300 children...

  11. The impact of high-intensity interval training versus moderate-intensity continuous training on vascular function: a systematic review and meta-analysis.

    Science.gov (United States)

    Ramos, Joyce S; Dalleck, Lance C; Tjonna, Arnt Erik; Beetham, Kassia S; Coombes, Jeff S

    2015-05-01

    Vascular dysfunction is a precursor to the atherosclerotic cascade, significantly increasing susceptibility to cardiovascular events such as myocardial infarction or stroke. Previous studies have revealed a strong relationship between vascular function and cardiorespiratory fitness (CRF). Thus, since high-intensity interval training (HIIT) is a potent method of improving CRF, several small randomized trials have investigated the impact on vascular function of HIIT relative to moderate-intensity continuous training (MICT). The aim of this study was to systematically review the evidence and quantify the impact on vascular function of HIIT compared with MICT. Three electronic databases (PubMed, Embase, and MEDLINE) were searched (until May 2014) for randomized trials comparing the effect of at least 2 weeks of HIIT and MICT on vascular function. HIIT protocols involved predominantly aerobic exercise at a high intensity, interspersed with active or passive recovery periods. We performed a meta-analysis to compare the mean difference in the change in vascular function assessed via brachial artery flow-mediated dilation (FMD) from baseline to post-intervention between HIIT and MICT. The impact of HIIT versus MICT on CRF, traditional cardiovascular disease (CVD) risk factors, and biomarkers associated with vascular function (oxidative stress, inflammation, and insulin resistance) was also reviewed across included studies. Seven randomized trials, including 182 patients, met the eligibility criteria and were included in the meta-analysis. A commonly used HIIT prescription was four intervals of 4 min (4 × 4 HIIT) at 85-95% of maximum or peak heart rate (HRmax/peak), interspersed with 3 min of active recovery at 60-70% HRmax/peak, three times per week for 12-16 weeks. Brachial artery FMD improved by 4.31 and 2.15% following HIIT and MICT, respectively. This resulted in a significant (p HIIT also had a greater tendency than MICT to induce positive effects on secondary

  12. A Novel Single-Domain Antibody Against von Willebrand Factor A1 Domain Resolves Leukocyte Recruitment and Vascular Leakage During Inflammation-Brief Report.

    Science.gov (United States)

    Aymé, Gabriel; Adam, Frédéric; Legendre, Paulette; Bazaa, Amine; Proulle, Valérie; Denis, Cécile V; Christophe, Olivier D; Lenting, Peter J

    2017-09-01

    von Willebrand factor (VWF) is crucial to hemostasis, but also plays a role in inflammatory processes. Unfortunately, no proper monoclonal antibodies to study VWF function in mice are currently available. We therefore aimed to generate single-domain antibodies (sdAbs) recognizing murine VWF and blocking its function in vivo. Llama-derived sdAbs recognizing both human and murine VWF were isolated via phage display technology. One of them (designated KB-VWF-006) recognized the VWF A1 domain with picomolar affinity. This sdAb avidity was strongly enhanced via dimerization using a triple Ala linker (KB-VWF-006bi). When administered in vivo to wild-type mice, KB-VWF-006bi dose dependently induced bleeding in a tail clip model. In 2 distinct models of inflammation, KB-VWF-006bi efficiently interfered with leukocyte recruitment and vascular leakage. KB-VWF-006bi is an sdAb recognizing the A1 domain of human VWF and murine VWF that interferes with VWF-platelet interactions in vivo. By using this sdAb, we now also show that the A1 domain is pertinent to the participation of VWF in the inflammatory response. © 2017 American Heart Association, Inc.

  13. The suppression of bromodomain and extra-terminal domain inhibits vascular inflammation by blocking NF-κB and MAPK activation.

    Science.gov (United States)

    Huang, Mingcheng; Zeng, Shan; Zou, Yaoyao; Shi, Maohua; Qiu, Qian; Xiao, Youjun; Chen, Guoqiang; Yang, Xiuyan; Liang, Liuqin; Xu, Hanshi

    2017-01-01

    There is increasing evidence indicating that bromodomain and extra-terminal domain (BET) proteins play a critical role in the regulation of immune and inflammatory responses; however, their contribution to vascular inflammation has not yet been elucidated. In this study, we investigated the effect of inhibiting BET bromodomain on vascular inflammation and the underlying mechanisms. HUVECs were isolated from fresh umbilical cords. JQ1, a specific BET bromodomain inhibitor, and Brd shRNA were used to evaluate the regulation of the BET proteins in vascular inflammation. Leukocyte adhesion to HUVECs was measure by an adhesion assay. Western blot or immunohistochemical analysis was used to detect the protein expression. Real-time PCR was used to evaluate mRNA expression. Leukocyte accumulation in vivo was determined by an acute lung inflammation model. BET bromodomain inhibition suppressed the expression of adhesion molecules induced by TNF-α- or LPS, including ICAM-1, VCAM-1 and E-selectin, and inhibited leukocyte adhesion to activated HUVEC monolayers. Treatment with JQ1 also attenuated the LPS-induced accumulation of leukocytes and expression of endothelial adhesion molecules in the acute lung inflammation model in vivo. Furthermore, BET bromodomain inhibition reduced the activity of p38 and JNK MAPKs and NF-κB in TNF-α-stimulated HUVECs. TNF-α-induced NF-κB activation was also blocked by inhibitors of p38 (SB203580) or JNK (SP600125). BET bromodomain is important for regulating endothelial inflammation. Strategies targeting endothelial BET bromodomain may provide a new therapeutic approach for controlling inflammatory-related diseases. © 2016 The British Pharmacological Society.

  14. Sex differences in obesity-induced hypertension and vascular dysfunction: a protective role for estrogen in adipose tissue inflammation?

    Science.gov (United States)

    Taylor, Lia E; Sullivan, Jennifer C

    2016-10-01

    Obesity is a potent predictor of cardiovascular disease and associated risk factors, including hypertension. Systemic inflammation has been suggested by a number of studies to be an important link between excess adiposity and hypertension, yet the majority of the studies have been conducted exclusively in males. This is problematic since women represent ∼53% of hypertensive cases and are more likely than men to be obese. There is a growing body of literature supporting a central role for immune cell activation in numerous experimental models of hypertension, and both the sex of the subject and the sex of the T cell have been shown to impact blood pressure (BP) responses to hypertensive stimuli. Moreover, sex steroid hormones play an important role in energy homeostasis, as well as in the regulation of immune responses; estrogen, in particular, has a well-known impact on both cardiovascular and metabolic disorders. Therefore, the purpose of this review is to examine whether sex or sex hormones regulate the role of the immune system in the development of hypertension and related vascular dysfunction in response to metabolic changes and stimuli, including a high-fat diet. Copyright © 2016 the American Physiological Society.

  15. Enhanced biocompatibility of CD47-functionalized vascular stents.

    Science.gov (United States)

    Slee, Joshua B; Alferiev, Ivan S; Nagaswami, Chandrasekaran; Weisel, John W; Levy, Robert J; Fishbein, Ilia; Stachelek, Stanley J

    2016-05-01

    The effectiveness of endovascular stents is hindered by in-stent restenosis (ISR), a secondary re-obstruction of treated arteries due to unresolved inflammation and activation of smooth muscle cells in the arterial wall. We previously demonstrated that immobilized CD47, a ubiquitously expressed transmembrane protein with an established role in immune evasion, can confer biocompatibility when appended to polymeric surfaces. In present studies, we test the hypothesis that CD47 immobilized onto metallic surfaces of stents can effectively inhibit the inflammatory response thus mitigating ISR. Recombinant CD47 (recCD47) or a peptide sequence corresponding to the Ig domain of CD47 (pepCD47), were attached to the surfaces of both 316L-grade stainless steel foils and stents using bisphosphonate coordination chemistry and thiol-based conjugation reactions to assess the anti-inflammatory properties of CD47-functionalized surfaces. Initial in vitro and ex vivo analysis demonstrated that both recCD47 and pepCD47 significantly reduced inflammatory cell attachment to steel surfaces without impeding on endothelial cell retention and expansion. Using a rat carotid stent model, we showed that pepCD47-functionalized stents prevented fibrin and platelet thrombus deposition, inhibited inflammatory cell attachment, and reduced restenosis by 30%. It is concluded that CD47-modified stent surfaces mitigate platelet and inflammatory cell attachment, thereby disrupting ISR pathophysiology. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Viral cross-class serpin inhibits vascular inflammation and T lymphocyte fratricide; a study in rodent models in vivo and human cell lines in vitro.

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    Kasinath Viswanathan

    Full Text Available Poxviruses express highly active inhibitors, including serine proteinase inhibitors (serpins, designed to target host immune defense pathways. Recent work has demonstrated clinical efficacy for a secreted, myxomaviral serpin, Serp-1, which targets the thrombotic and thrombolytic proteases, suggesting that other viral serpins may have therapeutic application. Serp-2 and CrmA are intracellular cross-class poxviral serpins, with entirely distinct functions from the Serp-1 protein. Serp-2 and CrmA block the serine protease granzyme B (GzmB and cysteine proteases, caspases 1 and 8, in apoptotic pathways, but have not been examined for extracellular anti-inflammatory activity. We examined the ability of these cross-class serpins to inhibit plaque growth after arterial damage or transplant and to reduce leukocyte apoptosis. We observed that purified Serp-2, but not CrmA, given as a systemic infusion after angioplasty, transplant, or cuff-compression injury markedly reduced plaque growth in mouse and rat models in vivo. Plaque growth was inhibited both locally at sites of surgical trauma, angioplasty or transplant, and systemically at non-injured sites in ApoE-deficient hyperlipidemic mice. With analysis in vitro of human cells in culture, Serp-2 selectively inhibited T cell caspase activity and blocked cytotoxic T cell (CTL mediated killing of T lymphocytes (termed fratricide. Conversely, both Serp-2 and CrmA inhibited monocyte apoptosis. Serp-2 inhibitory activity was significantly compromised either in vitro with GzmB antibody or in vivo in ApoE/GzmB double knockout mice. Conclusions The viral cross-class serpin, Serp-2, that targets both apoptotic and inflammatory pathways, reduces vascular inflammation in a GzmB-dependent fashion in vivo, and inhibits human T cell apoptosis in vitro. These findings indicate that therapies targeting Granzyme B and/or T cell apoptosis may be used to inhibit T lymphocyte apoptosis and inflammation in response to

  17. Tissue Transglutaminase Modulates Vascular Stiffness and Function Through Crosslinking-Dependent and Crosslinking-Independent Functions.

    Science.gov (United States)

    Steppan, Jochen; Bergman, Yehudit; Viegas, Kayla; Armstrong, Dinani; Tan, Siqi; Wang, Huilei; Melucci, Sean; Hori, Daijiro; Park, Sung Yong; Barreto, Sebastian F; Isak, Abraham; Jandu, Sandeep; Flavahan, Nicholas; Butlin, Mark; An, Steven S; Avolio, Alberto; Berkowitz, Dan E; Halushka, Marc K; Santhanam, Lakshmi

    2017-02-03

    The structural elements of the vascular wall, namely, extracellular matrix and smooth muscle cells (SMCs), contribute to the overall stiffness of the vessel. In this study, we examined the crosslinking-dependent and crosslinking-independent roles of tissue transglutaminase (TG2) in vascular function and stiffness. SMCs were isolated from the aortae of TG2-/- and wild-type (WT) mice. Cell adhesion was examined by using electrical cell-substrate impedance sensing and PicoGreen assay. Cell motility was examined using a Boyden chamber assay. Cell proliferation was examined by electrical cell-substrate impedance sensing and EdU incorporation assays. Cell micromechanics were studied using magnetic torsion cytometry and spontaneous nanobead tracer motions. Aortic mechanics were examined by tensile testing. Vasoreactivity was studied by wire myography. SMCs from TG2-/- mice had delayed adhesion, reduced motility, and accelerated de-adhesion and proliferation rates compared with those from WT. TG2-/- SMCs were stiffer and displayed fewer cytoskeletal remodeling events than WT. Collagen assembly was delayed in TG2-/- SMCs and recovered with adenoviral transduction of TG2. Aortic rings from TG2-/- mice were less stiff than those from WT; stiffness was partly recovered by incubation with guinea pig liver TG2 independent of crosslinking function. TG2-/- rings showed augmented response to phenylephrine-mediated vasoconstriction when compared with WT. In human coronary arteries, vascular media and plaque, high abundance of fibronectin expression, and colocalization with TG2 were observed. TG2 modulates vascular function/tone by altering SMC contractility independent of its crosslinking function and contributes to vascular stiffness by regulating SMC proliferation and matrix remodeling. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  18. Angiogenesis, inflammation and endothelial function in postmenopausal women screened for the metabolic syndrome.

    Science.gov (United States)

    Chedraui, Peter; Escobar, Gustavo S; Pérez-López, Faustino R; Palla, Giulia; Montt-Guevara, Magdalena; Cecchi, Elena; Genazzani, Andrea R; Simoncini, Tommaso

    2014-04-01

    Prevalence of the metabolic syndrome (METS) increases after the menopause; nevertheless, concomitant vascular, inflammatory and endothelial changes have not been completely elucidated. To measure serum markers of angiogenesis, inflammation and endothelial function in postmenopausal women screened for the METS. Serum of 100 postmenopausal women was analyzed for angiopoietin-2, interleukin-8 (IL-8), soluble FAS ligand (sFASL), interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-α), soluble CD40 ligand (sCD40L), plasminogen activator inhibitor-1 (PAI-1), and urokinase-type plasminogen activator (uPA). Comparisons were made in accordance to the presence or not of the METS and each of its components. Modified Adult Treatment Panel III criteria were used to define the METS. Women with the METS (n=57) had similar age and time since menopause as compared to those without the syndrome (n=43). In general, women with the METS displayed a trend for higher levels of the analyzed markers. Nevertheless, only IL-6 levels were found to be significantly higher and uPA levels significantly lower among METS women as compared to those without the syndrome. When analyte levels were compared as to presenting or not each of the diagnostic features of the METS, it was found that IL-6 levels were higher among women with abdominal obesity, low HDL-C and high triglyceride levels. Women with low HDL-C and high triglyceride levels presented significantly lower uPA levels and those with high glucose and low HDL-C displayed significantly higher sCD40L levels. Postmenopausal women with the METS in this sample displayed higher IL-6 (inflammation) and lower uPA levels (endothelial dysfunction). These were mainly related to metabolic and lipid abnormalities. More research is warranted in this regard. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. Human HOXA5 homeodomain enhances protein transduction and its application to vascular inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ji Young [Infectious Signaling Network Research Center and Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747 (Korea, Republic of); Park, Kyoung sook [BioNanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806 (Korea, Republic of); Cho, Eun Jung; Joo, Hee Kyoung; Lee, Sang Ki; Lee, Sang Do; Park, Jin Bong [Infectious Signaling Network Research Center and Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747 (Korea, Republic of); Chang, Seok Jong [Department of Physiology, College of Medicine, Seonam University, Namwon 590-170 (Korea, Republic of); Jeon, Byeong Hwa, E-mail: bhjeon@cnu.ac.kr [Infectious Signaling Network Research Center and Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747 (Korea, Republic of)

    2011-07-01

    Highlights: {yields} We have developed an E. coli protein expression vector including human specific gene sequences for protein cellular delivery. {yields} The plasmid was generated by ligation the nucleotides 770-817 of the homeobox A5 mRNA sequence. {yields} HOXA5-APE1/Ref-1 inhibited TNF-alpha-induced monocyte adhesion to endothelial cells. {yields} Human HOXA5-PTD vector provides a powerful research tools for uncovering cellular functions of proteins or for the generation of human PTD-containing proteins. -- Abstract: Cellular protein delivery is an emerging technique by which exogenous recombinant proteins are delivered into mammalian cells across the membrane. We have developed an Escherichia coli expression vector including human specific gene sequences for protein cellular delivery. The plasmid was generated by ligation the nucleotides 770-817 of the homeobox A5 mRNA sequence which was matched with protein transduction domain (PTD) of homeodomain protein A5 (HOXA5) into pET expression vector. The cellular uptake of HOXA5-PTD-EGFP was detected in 1 min and its transduction reached a maximum at 1 h within cell lysates. The cellular uptake of HOXA5-EGFP at 37 {sup o}C was greater than in 4 {sup o}C. For study for the functional role of human HOXA5-PTD, we purified HOXA5-APE1/Ref-1 and applied it on monocyte adhesion. Pretreatment with HOXA5-APE1/Ref-1 (100 nM) inhibited TNF-{alpha}-induced monocyte adhesion to endothelial cells, compared with HOXA5-EGFP. Taken together, our data suggested that human HOXA5-PTD vector provides a powerful research tools for uncovering cellular functions of proteins or for the generation of human PTD-containing proteins.

  20. Review of gestational diabetes mellitus effects on vascular structure and function.

    Science.gov (United States)

    Jensen, Louise A; Chik, Constance L; Ryan, Edmond A

    2016-05-01

    Vascular dysfunction has been described in women with a history of gestational diabetes mellitus. Furthermore, previous gestational diabetes mellitus increases the risk of developing Type 2 diabetes mellitus, a risk factor for cardiovascular disease. Factors contributing to vascular changes remain uncertain. The aim of this review was to summarize vascular structure and function changes found to occur in women with previous gestational diabetes mellitus and to identify factors that contribute to vascular dysfunction. A systematic search of electronic databases yielded 15 publications from 1998 to March 2014 that met the inclusion criteria. Our review confirmed that previous gestational diabetes mellitus contributes to vascular dysfunction, and the most consistent risk factor associated with previous gestational diabetes mellitus and vascular dysfunction was elevated body mass index. Heterogeneity existed across studies in determining the relationship of glycaemic levels and insulin resistance to vascular dysfunction. © The Author(s) 2016.

  1. Distribution and functional traits of charophytes and vascular plants

    DEFF Research Database (Denmark)

    Båstrup-Spohr, Lars

    A large variety of plant species of very different evolutionary origin are found within and along the margins of aquatic ecosystems. These species have very different adaptations depending on the particular environmental condition under which they grow. This thesis examines the role of these adap......A large variety of plant species of very different evolutionary origin are found within and along the margins of aquatic ecosystems. These species have very different adaptations depending on the particular environmental condition under which they grow. This thesis examines the role...... of these adaptations or functional traits for the distribution on large scales and along specific environmental gradients. Characean algae (charophytes) are an ancient group of aquatic plants found in most aquatic ecosystems. I confirmed that they have declined markedly during the 20th century, most likely...... rare species are specialists in particular environments, while the abundant species have traits such as broad salinity tolerance, tall shoots, vegetative reproduction and variable life form. Vascular plants, in contrast to charophytes, occupy the entire gradient from submerged to drained conditions...

  2. HIV infection, antiretroviral therapy, and measures of endothelial function, inflammation, metabolism, and oxidative stress.

    Directory of Open Access Journals (Sweden)

    Andrew Dysangco

    Full Text Available HIV-infected patients have an increased risk of cardiovascular disease (CVD. Impaired endothelial function is an early risk factor for CVD in the general population. It is presumed that HIV infection is associated with impaired endothelial function, but results have been inconsistent.Our objectives were to determine the relationships between HIV infection, virologic suppression with antiretroviral therapy (ART, in vivo measures of conduit artery and microvascular endothelial function, and circulating biomarkers of pathways associated with CVD.We performed a cross-sectional analysis of three prospectively enrolled groups from a single center: 28 were HIV-infected and virologically-suppressed on a regimen of FTC/TDF/EFV (HIV+ART+, 44 were HIV-infected but not on ART (HIV+ART-, and 39 were HIV-uninfected healthy volunteers (HIV- matched to the HIV+ART- group for age, sex, smoking status, and height. None had diabetes, uncontrolled hypertension, known CVD, or other pro-inflammatory condition. Flow mediated dilation (FMD, nitroglycerin-mediated dilation (NTGMD, reactive hyperemia velocity time integral (RHVTI, and FMD/RHVTI of the brachial artery were measured, as well as circulating biomarkers of systemic inflammation, metabolism, oxidative stress, and endothelial activation.No significant differences were found amongst the three groups in FMD (P = 0.46, NTGMD (P = 0.42, RHVTI (P = 0.17, and FMD/RHVTI (P = 0.22 in unadjusted comparisons. Adjusted ANOVA models which included brachial artery diameter, demographics, and conventional CVD risk factors did not appreciably change these findings. In pairwise comparisons, the HIV+ART- group had significantly higher soluble tumor necrosis factor receptor II, soluble CD163, β-2 microglobulin, interferon-γ- induced protein-10, tissue inhibitor of metalloproteinase-1, and vascular cell adhesion molecule-1 compared to the other two groups (all p<0.05. Correlates of endothelial function differed between study

  3. Diesel exhaust particulate induces pulmonary and systemic inflammation in rats without impairing endothelial function ex vivo or in vivo

    Directory of Open Access Journals (Sweden)

    Robertson Sarah

    2012-04-01

    Full Text Available Abstract Background Inhalation of diesel exhaust impairs vascular function in man, by a mechanism that has yet to be fully established. We hypothesised that pulmonary exposure to diesel exhaust particles (DEP would cause endothelial dysfunction in rats as a consequence of pulmonary and systemic inflammation. Methods Wistar rats were exposed to DEP (0.5 mg or saline vehicle by intratracheal instillation and hind-limb blood flow, blood pressure and heart rate were monitored in situ 6 or 24 h after exposure. Vascular function was tested by administration of the endothelium-dependent vasodilator acetylcholine (ACh and the endothelium-independent vasodilator sodium nitroprusside (SNP in vivo and ex vivo in isolated rings of thoracic aorta, femoral and mesenteric artery from DEP exposed rats. Bronchoalveolar lavage fluid (BALF and blood plasma were collected to assess pulmonary (cell differentials, protein levels & interleukin-6 (IL-6 and systemic (IL-6, tumour necrosis factor alpha (TNFα and C-reactive protein (CRP inflammation, respectively. Results DEP instillation increased cell counts, total protein and IL-6 in BALF 6 h after exposure, while levels of IL-6 and TNFα were only raised in blood 24 h after DEP exposure. DEP had no effect on the increased hind-limb blood flow induced by ACh in vivo at 6 or 24 h. However, responses to SNP were impaired at both time points. In contrast, ex vivo responses to ACh and SNP were unaltered in arteries isolated from rats exposed to DEP. Conclusions Exposure of rats to DEP induces both pulmonary and systemic inflammation, but does not modify endothelium-dependent vasodilatation. Other mechanisms in vivo limit dilator responses to SNP and these require further investigation.

  4. Sequential analysis of surfactant, lung function and inflammation in cystic fibrosis patients

    Directory of Open Access Journals (Sweden)

    Paul Karl

    2005-11-01

    Full Text Available Abstract Background In a cross-sectional analysis of cystic fibrosis (CF patients with mild lung disease, reduced surfactant activity was correlated to increased neutrophilic airway inflammation, but not to lung function. So far, longitudinal measurements of surfactant function in CF patients are lacking and it remains unclear how these alterations relate to the progression of airway inflammation as well as decline in pulmonary function over time. Methods As part of the BEAT trial, a longitudinal study to assess the course of airway inflammation in CF, we studied lung function, surfactant function and endobronchial inflammation using bronchoalveolar lavage fluid from 20 CF patients with normal pulmonary function (median FEV1 94% of predicted at three times over a three year period. Results There was a progressive loss of surfactant function, assessed as minimal surface tension. The decline in surfactant function was negatively correlated to an increase in neutrophilic inflammation and a decrease in lung function, assessed by FEV1, MEF75/25%VC, and MEF25%VC. The concentrations of the surfactant specific proteins A, C and D did not change, whereas SP-B increased during this time period. Conclusion Our findings suggest a link between loss of surfactant function driven by progressive airway inflammation and loss of small airway function in CF patients with limited lung disease.

  5. Age-related Impairment of Vascular Structure and Functions.

    Science.gov (United States)

    Xu, Xianglai; Wang, Brian; Ren, Changhong; Hu, Jiangnan; Greenberg, David A; Chen, Tianxiang; Xie, Liping; Jin, Kunlin

    2017-10-01

    Among age-related diseases, cardiovascular and cerebrovascular diseases are major causes of death. Vascular dysfunction is a key characteristic of these diseases wherein age is an independent and essential risk factor. The present work will review morphological alterations of aging vessels in-depth, which includes the discussion of age-related microvessel loss and changes to vasculature involving the capillary basement membrane, intima, media, and adventitia as well as the accompanying vascular dysfunctions arising from these alterations.

  6. Endothelial cell-borne platelet bridges selectively recruit monocytes in human and mouse models of vascular inflammation.

    Science.gov (United States)

    Kuckleburg, Christopher J; Yates, Clara M; Kalia, Neena; Zhao, Yan; Nash, Gerard B; Watson, Steve P; Rainger, George Ed

    2011-07-01

    Cells of the monocyte lineage are the most abundant inflammatory cells found in atherosclerotic lesions. Dominance of the inflammatory infiltrate by monocytes indicates that there is a disease-driven mechanism supporting their selective recruitment. Previous studies have demonstrated that interactions between endothelial cells (ECs) and platelets may promote monocyte recruitment. In this study, we sought to expand on this knowledge using a complex coculture model of the diseased vessel wall. Using primary human cells in an in vitro flow-based adhesion assay, we found that secretory arterial smooth muscle cells (SMCs), cocultured with ECs, promote preferential recruitment of monocytes from blood in a TGF-β1-dependent manner. Approximately 85% of leucocytes recruited to the endothelium were CD14(+). Formation of adhesive platelet bridges on ECs was essential for monocyte recruitment as platelet removal or inhibition of adhesion to the ECs abolished monocyte recruitment. Monocytes were recruited from flow by platelet P-selectin and activated by EC-derived CC chemokine ligand 2 (CCL2), although the presentation of CCL2 to adherent monocytes was dependent upon platelet activation and release of CXC chemokine ligand 4 (CXCL4). In an intravital model of TGF-β1-driven vascular inflammation in mice, platelets were also necessary for efficient leucocyte recruitment to vessels of the microcirculation in the cremaster muscle. In this study, we have demonstrated that stromal cells found within the diseased artery wall may promote the preferential recruitment of monocytes and this is achieved by establishing a cascade of interactions between SMCs, ECs, platelets, and monocytes.

  7. Genistein prevents hyperglycemia-induced monocyte adhesion to human aortic endothelial cells through preservation of the cAMP signaling pathway and ameliorates vascular inflammation in obese diabetic mice

    National Research Council Canada - National Science Library

    Babu, Pon Velayutham Anandh; Si, Hongwei; Fu, Zhuo; Zhen, Wei; Liu, Dongmin

    2012-01-01

    ...) interaction is the key event in the pathogenesis of atherosclerosis in diabetes. Here, we investigated the effect of isoflavone genistein on hyperglycemia-stimulated vascular inflammation. Human aortic EC (HAEC...

  8. Impact of AT2-receptor stimulation on vascular biology, kidney function, and blood pressure

    Directory of Open Access Journals (Sweden)

    Danyel LA

    2013-11-01

    Full Text Available Leon A Danyel,1 Patrick Schmerler,1 Ludovit Paulis,1–3 Thomas Unger,4 U Muscha Steckelings1,5 1Center for Cardiovascular Research, Institute of Pharmacology, Charité Medical Faculty, Berlin, Germany; 2Institute of Pathophysiology, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic; 3Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Slovak Republic; 4CARIM, Maastricht University, Maastricht, the Netherlands; 5Institute of Molecular Medicine, Department of Cardiovascular and Renal Physiology, University of Southern Denmark, Odense, Denmark Abstract: The angiotensin type 2 receptor (AT2R and the receptor MAS are receptors within the renin–angiotensin system, which mediate tissue-protective actions such as anti-inflammation, antifibrosis, and antiapoptosis. In recent years, several programs have been launched in order to develop drugs that act as agonists on the AT2R or MAS to take therapeutic advantage of the protective and regenerative properties of these receptors. This review article will focus on recent data obtained in preclinical animal and in vitro models with new AT2R-agonistic molecules (Compound 21 and β-amino acid substituted angiotensin II and with relevance for blood pressure (BP regulation or hypertensive end-organ damage. These data will include studies on vasodilation/vasoconstriction in isolated resistance arteries ex vivo, studies on kidney function, studies on vascular remodeling, and studies that measured the net effect of AT2R stimulation on BP in vivo. Current data indicate that although AT2R stimulation causes vasodilation ex vivo and promotes natriuresis, it does not alter BP levels in vivo acutely – at least as long as there is no additional low-dose blockade of AT1R. However, AT2R stimulation alone is able to attenuate hypertension-induced vascular remodeling and reduce arterial stiffening, which in more chronic settings and together with the natriuretic

  9. Genistein Prevents Hyperglycemia-Induced Monocyte Adhesion to Human Aortic Endothelial Cells through Preservation of the cAMP Signaling Pathway and Ameliorates Vascular Inflammation in Obese Diabetic Mice123

    OpenAIRE

    Babu, Pon Velayutham Anandh; Si, Hongwei; Fu, Zhuo; Zhen, Wei; Liu, Dongmin

    2012-01-01

    Hyperglycemia-induced vascular inflammation resulting in the enhanced monocyte-endothelial cell (EC) interaction is the key event in the pathogenesis of atherosclerosis in diabetes. Here, we investigated the effect of isoflavone genistein on hyperglycemia-stimulated vascular inflammation. Human aortic EC (HAEC) were pretreated with genistein before the addition of high glucose (HG; 25 mmol/L) for 48 h. Genistein at a physiological concentration (0.1 μmol/L) significantly inhibited HG-induced ...

  10. Impact of shear rate modulation on vascular function in humans.

    Science.gov (United States)

    Tinken, Toni M; Thijssen, Dick H J; Hopkins, Nicola; Black, Mark A; Dawson, Ellen A; Minson, Christopher T; Newcomer, Sean C; Laughlin, M Harold; Cable, N Timothy; Green, Daniel J

    2009-08-01

    Shear stress is an important stimulus to arterial adaptation in response to exercise and training in humans. We recently observed significant reverse arterial flow and shear during exercise and different antegrade/retrograde patterns of shear and flow in response to different types of exercise. The purpose of this study was to simultaneously examine flow-mediated dilation, a largely NO-mediated vasodilator response, in both brachial arteries of healthy young men before and after 30-minute interventions consisting of bilateral forearm heating, recumbent leg cycling, and bilateral handgrip exercise. During each intervention, a cuff inflated to 60 mm Hg was placed on 1 arm to unilaterally manipulate the shear rate stimulus. In the noncuffed arm, antegrade flow and shear increased similarly in response to each intervention (ANOVA; P<0.001, no interaction between interventions; P=0.71). Baseline flow-mediated dilation (4.6%, 6.9%, and 6.7%) increased similarly in response to heating, handgrip, and cycling (8.1%, 10.4%, and 8.9%, ANOVA; P<0.001, no interaction; P=0.89). In contrast, cuffed arm antegrade shear rate was lower than in the noncuffed arm for all of the conditions (P<0.05), and the increase in flow-mediated dilation was abolished in this arm (4.7%, 6.7%, and 6.1%; 2-way ANOVA: all conditions interacted P<0.05). These results suggest that differences in the magnitude of antegrade shear rate transduce differences in endothelial vasodilator function in humans, a finding that may have relevance for the impact of different exercise interventions on vascular adaptation in humans.

  11. Skin Blood Flow and Vascular Endothelium Function in Uremia.

    Science.gov (United States)

    Smogorzewski, Miroslaw J

    2017-11-01

    Prevalence of dermatological disorder in patients with end-stage kidney disease is estimated as 50% to 100% in various studies. Some of the skin lesions are specific for the diseases causing chronic kidney disease (CKD), some are associated with CKD, and still others are the dermatological manifestation of uremia. Microangiopathy was also found in both arterioles and venule in the skin biopsy of "normal looking" skin in patients with end-stage kidney disease. In a cross-sectional study in patients on dialysis, we measured skin blood flow (SBF) using laser Doppler device in a standardized way at various areas of lower extremities at 2 different local skin temperatures: 35°C and 44°C. Local heating increases skin perfusion by mechanisms dependent on nitric oxide (NO). SBF was impaired in CKD patients Stage 5 on HD, particularly in those with diabetes mellitus as a cause of CKD. The reduced response in the SBF to the heat in our patients may be due to decreased generation of NO in uremia. Endothelium-dependent vasodilatation in patients on dialysis and the response of the skin microcirculation to acetylcholine was diminished in hypertensive patients on dialysis. Similarly, patients with diabetes mellitus had decreased SBF during intradermal microdialysis with a NO synthase inhibitor. Multiple uremic toxins have been studied in vitro and show to cause various degree of endothelial cell dysfunction. Unfortunately, no clear benefit has been described in CKD patients to different intervention aimed to reduce uremic toxin effect on endothelium. There are no long-term data on the factors which can modify endothelium function in uremia, but non pharmacologic interventions, diet, and several pharmacologic approaches could be beneficial. Measurement of SBF can be useful in evaluation of vasculopathy in CKD population and can potentially be used for assessment of vascular response during specific clinical intervention. Copyright © 2017. Published by Elsevier Inc.

  12. Dark chocolate consumption improves leukocyte adhesion factors and vascular function in overweight men.

    Science.gov (United States)

    Esser, Diederik; Mars, Monica; Oosterink, Els; Stalmach, Angelique; Müller, Michael; Afman, Lydia A

    2014-03-01

    Flavanol-enriched chocolate consumption increases endothelium-dependent vasodilation. Most research so far has focused on flow-mediated dilation (FMD) only; the effects on other factors relevant to endothelial health, such as inflammation and leukocyte adhesion, have hardly been addressed. We investigated whether consumption of regular dark chocolate also affects other markers of endothelial health, and whether chocolate enrichment with flavanols has additional benefits. In a randomized double-blind crossover study, the effects of acute and of 4 wk daily consumption of high flavanol chocolate (HFC) and normal flavanol chocolate (NFC) on FMD, augmentation index (AIX), leukocyte count, plasma cytokines, and leukocyte cell surface molecules in overweight men (age 45-70 yr) were investigated. Sensory profiles and motivation scores to eat chocolate were also collected. Findings showed that a 4 wk chocolate intake increased FMD by 1%, which was paralleled by a decreased AIX of 1%, decreased leukocyte cell count, decreased plasma sICAM1 and sICAM3, and decreased leukocyte adhesion marker expression (Pchocolate. This study provides new insights on how chocolate affects endothelial health by demonstrating that chocolate consumption, besides improving vascular function, also lowers the adherence capacity of leukocytes in the circulation.

  13. Targeting Vascular Endothelial Growth Factor Receptor 2 and Protein Kinase D1 Related Pathways by a Multiple Kinase Inhibitor in Angiogenesis and Inflammation Related Processes In Vitro

    Science.gov (United States)

    Varga, Attila; Gyulavári, Pál; Greff, Zoltán; Futosi, Krisztina; Németh, Tamás; Simon-Szabó, Laura; Kerekes, Krisztina; Szántai-Kis, Csaba; Brauswetter, Diána; Kokas, Márton; Borbély, Gábor; Erdei, Anna; Mócsai, Attila; Kéri, György; Vántus, Tibor

    2015-01-01

    Emerging evidence suggests that the vascular endothelial growth factor receptor 2 (VEGFR2) and protein kinase D1 (PKD1) signaling axis plays a critical role in normal and pathological angiogenesis and inflammation related processes. Despite all efforts, the currently available therapeutic interventions are limited. Prior studies have also proved that a multiple target inhibitor can be more efficient compared to a single target one. Therefore, development of novel inflammatory pathway-specific inhibitors would be of great value. To test this possibility, we screened our molecular library using recombinant kinase assays and identified the previously described compound VCC251801 with strong inhibitory effect on both VEGFR2 and PKD1. We further analyzed the effect of VCC251801 in the endothelium-derived EA.hy926 cell line and in different inflammatory cell types. In EA.hy926 cells, VCC251801 potently inhibited the intracellular activation and signaling of VEGFR2 and PKD1 which inhibition eventually resulted in diminished cell proliferation. In this model, our compound was also an efficient inhibitor of in vitro angiogenesis by interfering with endothelial cell migration and tube formation processes. Our results from functional assays in inflammatory cellular models such as neutrophils and mast cells suggested an anti-inflammatory effect of VCC251801. The neutrophil study showed that VCC251801 specifically blocked the immobilized immune-complex and the adhesion dependent TNF-α -fibrinogen stimulated neutrophil activation. Furthermore, similar results were found in mast cell degranulation assay where VCC251801 caused significant reduction of mast cell response. In summary, we described a novel function of a multiple kinase inhibitor which strongly inhibits the VEGFR2-PKD1 signaling and might be a novel inhibitor of pathological inflammatory pathways. PMID:25874616

  14. Targeting vascular endothelial growth factor receptor 2 and protein kinase D1 related pathways by a multiple kinase inhibitor in angiogenesis and inflammation related processes in vitro.

    Directory of Open Access Journals (Sweden)

    Attila Varga

    Full Text Available Emerging evidence suggests that the vascular endothelial growth factor receptor 2 (VEGFR2 and protein kinase D1 (PKD1 signaling axis plays a critical role in normal and pathological angiogenesis and inflammation related processes. Despite all efforts, the currently available therapeutic interventions are limited. Prior studies have also proved that a multiple target inhibitor can be more efficient compared to a single target one. Therefore, development of novel inflammatory pathway-specific inhibitors would be of great value. To test this possibility, we screened our molecular library using recombinant kinase assays and identified the previously described compound VCC251801 with strong inhibitory effect on both VEGFR2 and PKD1. We further analyzed the effect of VCC251801 in the endothelium-derived EA.hy926 cell line and in different inflammatory cell types. In EA.hy926 cells, VCC251801 potently inhibited the intracellular activation and signaling of VEGFR2 and PKD1 which inhibition eventually resulted in diminished cell proliferation. In this model, our compound was also an efficient inhibitor of in vitro angiogenesis by interfering with endothelial cell migration and tube formation processes. Our results from functional assays in inflammatory cellular models such as neutrophils and mast cells suggested an anti-inflammatory effect of VCC251801. The neutrophil study showed that VCC251801 specifically blocked the immobilized immune-complex and the adhesion dependent TNF-α -fibrinogen stimulated neutrophil activation. Furthermore, similar results were found in mast cell degranulation assay where VCC251801 caused significant reduction of mast cell response. In summary, we described a novel function of a multiple kinase inhibitor which strongly inhibits the VEGFR2-PKD1 signaling and might be a novel inhibitor of pathological inflammatory pathways.

  15. Biomarkers of coagulation, fibrinolysis, endothelial function, and inflammation in arterialized venous blood

    DEFF Research Database (Denmark)

    Gram, Anne Sofie; Skov, Jane; Ploug, Thorkil

    2014-01-01

    Effects of venous blood arterialization on cardiovascular risk markers are still unknown. We evaluated biomarkers of inflammation, coagulation, fibrinolysis, and endothelial function in arterialized compared with regular venous blood. Cubital venipunctures were obtained from 10 healthy volunteers...

  16. Systemic Vascular Function Is Associated with Muscular Power in Older Adults

    Directory of Open Access Journals (Sweden)

    Kevin S. Heffernan

    2012-01-01

    Full Text Available Age-associated loss of muscular strength and muscular power is a critical determinant of loss of physical function and progression to disability in older adults. In this study, we examined the association of systemic vascular function and measures of muscle strength and power in older adults. Measures of vascular endothelial function included brachial artery flow-mediated dilation (FMD and the pulse wave amplitude reactive hyperemia index (PWA-RHI. Augmentation index (AIx was taken as a measure of systemic vascular function related to arterial stiffness and wave reflection. Measures of muscular strength included one repetition maximum (1RM for a bilateral leg press. Peak muscular power was measured during 5 repetitions performed as fast as possible for bilateral leg press at 40% 1RM. Muscular power was associated with brachial FMD (r=0.43, P<0.05, PWA-RHI (r=0.42, P<0.05, and AIx (r=−0.54, P<0.05. Muscular strength was not associated with any measure of vascular function. In conclusion, systemic vascular function is associated with lower-limb muscular power but not muscular strength in older adults. Whether loss of muscular power with aging contributes to systemic vascular deconditioning or vascular dysfunction contributes to decrements in muscular power remains to be determined.

  17. Vascular biology of preeclampsia.

    Science.gov (United States)

    Myatt, L; Webster, R P

    2009-03-01

    Preeclampsia, a pregnancy-specific syndrome characterized by hypertension, proteinuria and edema, resolves on delivery of the placenta. Normal pregnancy is itself characterized by systemic inflammation, oxidative stress and alterations in levels of angiogenic factors and vascular reactivity. This is exacerbated in preeclampsia with an associated breakdown of compensatory mechanisms, eventually leading to placental and vascular dysfunction. The underlying pathology of preeclampsia is thought to be a relatively hypoxic or ischemic placenta. Both the placenta and maternal vasculatures are major sources of reactive oxygen and nitrogen species which can interact to produce peroxynitrite a powerful prooxidant that covalently modifies proteins by nitration of tyrosine residues, to possibly alter vascular function in preeclampsia. The linkage between placental hypoxia and maternal vascular dysfunction has been proposed to be via placental syncytiotrophoblast basement membranes shed by the placenta or via angiogenic factors which include soluble flt1 and endoglin secreted by the placenta that bind vascular endothelial growth factor (VEGF) and placental growth factor (PIGF) in the maternal circulation. There is also abundant evidence of altered reactivity of the maternal and placental vasculature and of the altered production of autocoids in preeclampsia. The occurrence of preeclampsia is increased in women with preexisting vascular disease and confers a long-term risk for development of cardiovascular disease. The vascular stress test of pregnancy thus identifies those women with a previously unrecognized at risk vascular system and promotes the development of preeclampsia. Preexisting maternal vascular dysfunction intensified by placental factors is possibly responsible for the individual pathologies of preeclampsia.

  18. Clopidogrel, a platelet P2Y12 receptor inhibitor, reduces vascular inflammation and angiotensin II induced-abdominal aortic aneurysm progression.

    Directory of Open Access Journals (Sweden)

    Ou Liu

    Full Text Available Medial degeneration and inflammation are features of abdominal aortic aneurysms (AAAs. However, the early inflammatory event initiating aneurysm formation remains to be identified. Activated platelets release abundant proinflammatory cytokines and are involved in initial inflammation in various vascular diseases. We investigated the role of platelets in progression of AAA in vivo and in vitro. Histological studies of tissues of patients with AAA revealed that the number of platelets was increased in aneurysm sites along with the increased infiltration of T lymphocytes and augmented angiogenesis. In a murine model of AAA, apolipoprotein E-knockout mice infused with 1,000 ng/kg/min angiotensin II, treatment with clopidogrel, an inhibitor of platelets, significantly suppressed aneurysm formation (47% decrease, P<0.05. The clopidogrel also suppressed changes in aortic expansion, elastic lamina degradation and inflammatory cytokine expression. Moreover, the infiltration of macrophages and production of matrix metalloproteinases (MMPs were also significantly reduced by clopidogrel treatment. In vitro incubation of macrophages with isolated platelets stimulated MMP activity by 45%. These results demonstrate a critical role for platelets in vascular inflammation and AAA progression.

  19. The plant vascular system: Evolution, development and functions

    Science.gov (United States)

    William J. Lucas; Andrew Groover; Raffael Lichtenberger; Kaori Furuta; Shri-Ram Yadav; Yka Helariutta; Xin-Qiang He; Hiroo Fukuda; Julie Kang; Siobhan M. Brady; John W. Patrick; John Sperry; Akiko Yoshida; Ana-Flor Lopez-Millan; Michael A. Grusak; Pradeep Kachroo

    2013-01-01

    The emergence of the tracheophyte-based vascular system of land plants had major impacts on the evolution of terrestrial biology, in general, through its role in facilitating the development of plants with increased stature, photosynthetic output, and ability to colonize a greatly expanded range of environmental habitats. Recently, considerable progress has been made...

  20. Netrin-1 Promotes Inflammation Resolution to Achieve Endothelialization of Small-Diameter Tissue Engineering Blood Vessels by Improving Endothelial Progenitor Cells Function In Situ.

    Science.gov (United States)

    Li, Yanzhao; Wan, Simin; Liu, Ge; Cai, Wang; Huo, Da; Li, Gang; Yang, Mingcan; Wang, Yuxin; Guan, Ge; Ding, Ning; Liu, Feila; Zeng, Wen; Zhu, Chuhong

    2017-12-01

    The transplant of small-diameter tissue engineering blood vessels (small-diameter TEBVs) (vascular replacement therapy often fails because of early onset thrombosis and long-standing chronic inflammation. The specific inflammation state involved in small-diameter TEBVs transplants remains unclear, and whether promoting inflammation resolution would be useful for small-diameter TEBVs therapy need study. The neural protuberant orientation factor 1 (Netrin-1) is found present in endothelial cells of natural blood vessels and has anti-inflammatory effects. This work generates netrin-1-modified small-diameter TEBVs by using layer-by-layer self-assembly to resolve the inflammation. The results show that netrin-1 reprograms macrophages (MΦ) to assume an anti-inflammatory phenotype and promotes the infiltration and subsequent efflux of MΦ from inflamed sites over time, which improves the local microenvironment and the function of early homing endothelial progenitor cells (EPCs). Small-diameter TEBVs modified by netrin-1 achieve endothelialization after 30 d and retain patency at 14 months. These findings suggest that promoting the resolution of inflammation in time is necessary to induce endothelialization of small-diameter TEBVs and prevent early thrombosis and problems associated with chronic inflammation. Furthermore, this work finds that the MΦ-derived exosomes can target and regulate EPCs, which may serve as a useful treatment for other inflammatory diseases.

  1. Rehmannia glutinosa (Gaertn.) DC. polysaccharide ameliorates hyperglycemia, hyperlipemia and vascular inflammation in streptozotocin-induced diabetic mice.

    Science.gov (United States)

    Zhou, Jun; Xu, Gang; Yan, Junyan; Li, Kaicheng; Bai, Zhaoshuai; Cheng, Weinan; Huang, Kaixun

    2015-04-22

    chemoattractant protein-1, MDA, and also the elevated blood levels of SOD and GPx activities in diabetic mice. Taken together, RGP can effectively ameliorate hyperglycemia, hyperlipemia, vascular inflammation and oxidative stress in STZ-induced diabetic mice, and thus may be a potential therapeutic option for type 1 diabetes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. The role of the vascular dendritic cell network in atherosclerosis

    Science.gov (United States)

    Alberts-Grill, Noah; Denning, Timothy L.; Rezvan, Amir

    2013-01-01

    A complex role has been described for dendritic cells (DCs) in the potentiation and control of vascular inflammation and atherosclerosis. Resident vascular DCs are found in the intima of atherosclerosis-prone vascular regions exposed to disturbed blood flow patterns. Several phenotypically and functionally distinct vascular DC subsets have been described. The functional heterogeneity of these cells and their contributions to vascular homeostasis, inflammation, and atherosclerosis are only recently beginning to emerge. Here, we review the available literature, characterizing the origin and function of known vascular DC subsets and their important role contributing to the balance of immune activation and immune tolerance governing vascular homeostasis under healthy conditions. We then discuss how homeostatic DC functions are disrupted during atherogenesis, leading to atherosclerosis. The effectiveness of DC-based “atherosclerosis vaccine” therapies in the treatment of atherosclerosis is also reviewed. We further provide suggestions for distinguishing DCs from macrophages and discuss important future directions for the field. PMID:23552284

  3. Evaluation of a static stretching intervention on vascular endothelial function and arterial stiffness.

    Science.gov (United States)

    Shinno, Hiromi; Kurose, Satoshi; Yamanaka, Yutaka; Higurashi, Kyoko; Fukushima, Yaeko; Tsutsumi, Hiromi; Kimura, Yutaka

    2017-06-01

    Maintenance and enhancement of vascular endothelial function contribute to the prevention of cardiovascular disease and prolong a healthy life expectancy. Given the reversible nature of vascular endothelial function, interventions to improve this function might prevent arteriosclerosis. Accordingly, we studied the effects of a 6-month static stretching intervention on vascular endothelial function (reactive hyperaemia peripheral arterial tonometry index: RH-PAT index) and arterial stiffness (brachial-ankle pulse wave velocity: baPWV) and investigated the reversibility of these effects after a 6-month detraining period following intervention completion. The study evaluated 22 healthy, non-smoking, premenopausal women aged ≥40 years. Subjects were randomly assigned to the full-intervention (n = 11; mean age: 48.6 ± 2.8 years) or a half-intervention that included a control period (n = 11; mean age: 46.9 ± 3.6 years). Body flexibility and vascular endothelial function improved significantly after 3 months of static stretching. In addition to these improvements, arterial stiffness improved significantly after a 6-month intervention. However, after a 6-month detraining period, vascular endothelial function, flexibility, and arterial stiffness all returned to preintervention conditions, demonstrating the reversibility of the obtained effects. A 3-month static stretching intervention was found to improve vascular endothelial function, and an additional 3-month intervention also improved arterial stiffness. However, these effects were reversed by detraining.

  4. Evaluation of metabolic syndrome and associations with inflammation and graft function in renal transplant recipients.

    Science.gov (United States)

    de Alencastro, Mariana Gascue; Lemos, Joana Raquel Nunes; Bastos, Nícia Maria Romano de Medeiros; Vicari, Alessandra Rosa; Gonçalves, Luiz Felipe Santos; Manfro, Roberto Ceratti

    2013-01-01

    Cardiovascular disease (CVD) is a major determinant of mortality in renal transplant recipients (RTR). Metabolic syndrome (MS) and chronic inflammation are currently considered non traditional risk factors for cardiovascular disease. This study evaluates the frequency of these conditions their associations with graft function. To evaluate the prevalence of metabolic syndrome (MS) and inflammation and their associations with graft function in renal transplant recipients. A cross-sectional study was carried out with 200 RTR. MS was defined by the NCEP-ATP III criteria. Inflammation was assessed by CRP levels. Renal function was assessed by GFR estimation using the MDRD equation. MS occurred in 71 patients (35.5%). Patients with MS had higher CPR and decreased GFR levels. Inflammation was present in 99 patients (49.5%). Mean waist perimeter, body mass index, triglycerides and serum total cholesterol were significantly higher in inflamed patients. An association between MS and inflammation was demonstrated, 48 (67.6%) patients with MS were inflamed and among those without MS the rate of inflamed patients was 39.5% (51 patients) (p inflammation. MS is negatively associated with graft function. The clinical implications of these findings must be evaluated in longitudinal studies.

  5. Akita spontaneously type 1 diabetic mice exhibit elevated vascular arginase and impaired vascular endothelial and nitrergic function.

    Directory of Open Access Journals (Sweden)

    Haroldo A Toque

    Full Text Available Elevated arginase (Arg activity is reported to be involved in diabetes-induced vascular endothelial dysfunction. It can reduce L-arginine availability to nitric oxide (NO synthase (NOS and NO production. Akita mice, a genetic non-obese type 1 diabetes model, recapitulate human diabetes. We determined the role of Arg in a time-course of diabetes-associated endothelial dysfunction in aorta and corpora cavernosa (CC from Akita mice.Endothelium-dependent relaxation, Arg and NOS activity, and protein expression levels of Arg and constitutive NOS were assessed in aortas and CC from Akita and non-diabetic wild type (WT mice at 4, 12 and 24 wks of age. Systolic blood pressure (SBP was assessed by tail cuff. In aorta and CC, Akita mice exhibited a progressive impairment of vascular endothelial and nitrergic function increased Arg activity and expression (Arg1 in aorta and both Arg1 and Arg2 in CC compared with that of age-matched WT mice. Treatment of aorta and CC from Akita mice with an Arg inhibitor (BEC or ABH reduced diabetes-induced elevation of Arg activity and restored endothelial and nitrergic function. Reduced levels of phospho-eNOS at Ser(1177 (in aorta and CC and nNOS expression (in CC were observed in Akita mice at 12 and 24 wks. Akita mice also had decreased NOS activity in aorta and CC at 12 and 24 wks that was restored by BEC treatment. Further, Akita mice exhibited moderately increased SBP at 24 wks and increased sensitivity to PE-induced contractions in aorta and sympathetic nerve stimulation in CC at 12 and 24 wks.Over 24 wks of diabetes in Akita mice, both aortic and cavernosal tissues exhibited increased Arg activity/expression, contributing to impaired endothelial and nitrergic function and reduced NO production. Our findings demonstrate involvement of Arg activity in diabetes-induced impairment of vascular function in Akita mouse.

  6. Aging Exacerbates Obesity-Induced Oxidative Stress and Inflammation in Perivascular Adipose Tissue in Mice: A Paracrine Mechanism Contributing to Vascular Redox Dysregulation and Inflammation

    OpenAIRE

    Bailey-Downs, Lora C.; Tucsek, Zsuzsanna; TOTH, Peter; Sosnowska, Danuta; Gautam, Tripti; Sonntag, William E.; Csiszar, Anna; Ungvari, Zoltan

    2012-01-01

    Obesity in the elderly individuals is increasing at alarming rates and there is evidence suggesting that elderly individuals are more vulnerable to the deleterious cardiovascular effects of obesity than younger individuals. However, the specific mechanisms through which aging and obesity interact to promote the development of cardiovascular disease remain unclear. The present study was designed to test the hypothesis that aging exacerbates obesity-induced inflammation in perivascular adipose ...

  7. Vascular calcification and cardiac function according to residual renal function in patients on hemodialysis with urination.

    Directory of Open Access Journals (Sweden)

    Dong Ho Shin

    Full Text Available Vascular calcification is common and may affect cardiac function in patients with end-stage renal disease (ESRD. However, little is known about the effect of residual renal function on vascular calcification and cardiac function in patients on hemodialysis.This study was conducted between January 2014 and January 2017. One hundred six patients with residual renal function on maintenance hemodialysis for 3 months were recruited. We used residual renal urea clearance (KRU to measure residual renal function. First, abdominal aortic calcification score (AACS and brachial-ankle pulse wave velocity (baPWV were measured in patients on hemodialysis. Second, we performed echocardiography and investigated new cardiovascular events after study enrollment.The median KRU was 0.9 (0.3-2.5 mL/min/1.73m2. AACS (4.0 [1.0-10.0] vs. 3.0 [0.0-8.0], p = 0.05 and baPWV (1836.1 ± 250.4 vs. 1676.8 ± 311.0 cm/s, p = 0.01 were significantly higher in patients with a KRU < 0.9 mL/min/1.73m2 than a KRU ≥ 0.9 mL/min/1.73m2. Log-KRU significantly negatively correlated with log-AACS (ß = -0.29, p = 0.002 and baPWV (ß = -0.19, P = 0.05 after factor adjustment. The proportion of left ventricular diastolic dysfunction was significantly higher in patients with a KRU < 0.9 mL/min/1.73m2 than with a KRU ≥ 0.9 mL/min/1.73m2 (67.9% vs. 49.1%, p = 0.05. Patients with a KRU < 0.9 mL/min/1.73m2 showed a higher tendency of cumulative cardiovascular events compared to those with a KRU ≥ 0.9 ml/min/1.73m2 (P = 0.08.Residual renal function was significantly associated with vascular calcification and left ventricular diastolic dysfunction in patients on hemodialysis.

  8. Systemic Inflammation in Duchenne Muscular Dystrophy: Association with Muscle Function and Nutritional Status

    Directory of Open Access Journals (Sweden)

    Oriana del Rocío Cruz-Guzmán

    2015-01-01

    Full Text Available Inflammation described in patients with Duchenne muscular dystrophy (DMD may be related to loss of muscle function or to obesity. It is unknown if circulating proinflammatory cytokines (IL-6, IL-1, and TNF-α levels are associated with muscle function. The purpose was to evaluate whether an association exists between systemic inflammation with muscle function and nutritional status in DMD patients. In 66 DMD patients without corticosteroid treatment, the following were evaluated in serum: cytokines (IL-1, IL-6, and TNF-α, C-reactive protein (CRP, leptin, adiponectin, and creatine kinase (CK. Muscle function was evaluated using Vignos Scale. Patients with better muscle function had the highest concentration of CK, IL-1, and TNF-α compared with less muscle function. No differences in IL-6 and adiponectin concentration were identified among groups with different levels of muscle function. Also, no differences were observed in the concentration of cytokines among groups with different nutritional status levels (underweight, normal weight, and overweight/obese. However, CRP and leptin were increased in the obese group compared with normal and underweight subjects. Systemic inflammation is increased in patients with better muscle function and decreases in DMD patients with poorer muscle function; nevertheless, systemic inflammation is similar among different levels of nutritional status in DMD patients.

  9. Vascular Function and Handgrip Strength in Rheumatoid Arthritis Patients

    Directory of Open Access Journals (Sweden)

    Mahmoud A. Alomari

    2012-01-01

    Full Text Available Objective. To examine the relationship of handgrip strength with forearm blood flow (BF and vascular resistance (VR in rheumatoid arthritis (RA patients. Methods. Forearm BF at rest (RBF and after upper arm occlusion (RHBF, and handgrip strength were examined in 78 individuals (RA=42 and controls (CT=36. Subsequently, VR at rest (RVR and after occlusion (RHVR were calculated. Results. The patients’ RBF (P=0.02 and RHBF (P=0.0001 were less, whereas RVR (P=0.002 and RHVR (P=0.0001 were greater as compared to the CTs. Similarly, handgrip strength was lower in the RAs (P=0.0001. Finally, handgrip strength was directly associated with RBF (r=0.43; P=0.0001, and RHBF (r=0.5; P=0.0001, and inversely related to RVR (r=-0.3; P=0.009 and RHVR (r=-0.3; P=0.007. Conclusion. The present study uniquely identifies an association between regional measures of forearm blood flow and handgrip strength in patients and healthy control. In addition, this study confirms the presence of vascular and muscle dysfunction in patients with rheumatoid arthritis, as evidenced by lower forearm blood flow indices, at rest and following occlusion, and lower handgrip strength as compared to healthy individuals.

  10. A functional module-based exploration between inflammation and cancer in esophagus

    Science.gov (United States)

    Liu, Nannan; Li, Chunhua; Huang, Yan; Yi, Ying; Bo, Wanlan; Li, Chunmiao; Li, Yue; Hu, Yongfei; Li, Kongning; Wang, Hong; Zhuang, Liwei; Fan, Huihui; Wang, Dong

    2015-01-01

    Inflammation contributing to the underlying progression of diverse human cancers has been generally appreciated, however, explorations into the molecular links between inflammation and cancer in esophagus are still at its early stage. In our study, we presented a functional module-based approach, in combination with multiple data resource (gene expression, protein-protein interactions (PPI), transcriptional and post-transcriptional regulations) to decipher the underlying links. Via mapping differentially expressed disease genes, functional disease modules were identified. As indicated, those common genes and interactions tended to play important roles in linking inflammation and cancer. Based on crosstalk analysis, we demonstrated that, although most disease genes were not shared by both kinds of modules, they might act through participating in the same or similar functions to complete the molecular links. Additionally, we applied pivot analysis to extract significant regulators for per significant crosstalk module pair. As shown, pivot regulators might manipulate vital parts of the module subnetworks, and then work together to bridge inflammation and cancer in esophagus. Collectively, based on our functional module analysis, we demonstrated that shared genes or interactions, significant crosstalk modules, and those significant pivot regulators were served as different functional parts underlying the molecular links between inflammation and cancer in esophagus. PMID:26489668

  11. Serum Superoxide Dismutase Is Associated with Vascular Structure and Function in Hypertensive and Diabetic Patients

    Directory of Open Access Journals (Sweden)

    Manuel A. Gómez-Marcos

    2016-01-01

    Full Text Available Oxidative stress is associated with cardiac and vascular defects leading to hypertension and atherosclerosis, being superoxide dismutase (SOD one of the main intracellular antioxidant defence mechanisms. Although several parameters of vascular function and structure have a predictive value for cardiovascular morbidity-mortality in hypertensive patients, there are no studies on the involvement of SOD serum levels with these vascular parameters. Thus, we assessed if SOD serum levels are correlated with parameters of vascular function and structure and with cardiovascular risk in hypertensive and type 2 diabetic patients. We enrolled 255 consecutive hypertensive and diabetic patients and 52 nondiabetic and nonhypertensive controls. SOD levels were measured with an enzyme-linked immunosorbent assay kit. Vascular function and structure were evaluated by pulse wave velocity, augmentation index, ambulatory arterial stiffness index, and carotid intima-media thickness. We detected negative correlations between SOD and pressure wave velocity, peripheral and central augmentation index and ambulatory arterial stiffness index, pulse pressure, and plasma HDL-cholesterol, as well as positive correlations between SOD and plasma uric acid and triglycerides. Our study shows that SOD is a marker of cardiovascular alterations in hypertensive and diabetic patients, since changes in its serum levels are correlated with alterations in vascular structure and function.

  12. miR-31 functions as a negative regulator of lymphatic vascular lineage-specific differentiation in vitro and vascular development in vivo

    NARCIS (Netherlands)

    Pedrioli, D.M.; Karpanen, T.; Dabouras, V.; Jurisic, G.; van de Hoek, G.; Shin, J.W.; Marino, D.; Kalin, R.E.; Leidel, S.; Cinelli, P.; Schulte-Merker, S.; Brandli, A.W.; Detmar, M.

    2010-01-01

    The lymphatic vascular system maintains tissue fluid homeostasis, helps mediate afferent immune responses, and promotes cancer metastasis. To address the role microRNAs (miRNAs) play in the development and function of the lymphatic vascular system, we defined the in vitro miRNA expression profiles

  13. Loss-of-Function Mutations in APOC3 and Risk of Ischemic Vascular Disease

    DEFF Research Database (Denmark)

    Jørgensen, Anders Berg; Frikke-Schmidt, Ruth; Nordestgaard, Børge G

    2014-01-01

    of ischemic cardiovascular disease in the general population is unknown. METHODS: Using data from 75,725 participants in two general-population studies, we first tested whether low levels of nonfasting triglycerides were associated with reduced risks of ischemic vascular disease and ischemic heart disease....... Second, we tested whether loss-of-function mutations in APOC3, which were associated with reduced levels of nonfasting triglycerides, were also associated with reduced risks of ischemic vascular disease and ischemic heart disease. During follow-up, ischemic vascular disease developed in 10...... (350 mg per deciliter) or more (hazard ratio for ischemic vascular disease, 0.43; 95% confidence interval [CI], 0.35 to 0.54; hazard ratio for ischemic heart disease, 0.40; 95% CI, 0.31 to 0.52). Heterozygosity for loss-of-function mutations in APOC3, as compared with no APOC3 mutations, was associated...

  14. The Differential Role of Hif1β/Arnt and the Hypoxic Response in Adipose Function, Fibrosis, and Inflammation

    Science.gov (United States)

    Lee, Kevin Y.; Gesta, Stephane; Boucher, Jeremie; Wang, Xiaohui L.; Kahn, C. Ronald

    2011-01-01

    In obesity, adipocytes distant from vasculature become hypoxic and dysfunctional. This hypoxic response is mediated by hypoxia inducible factors (Hif1α, Hif2α, and Hif3α), and their obligate partner Hif1β (Arnt). We show that mice lacking Hif1β in fat (FH1βKO) are lean, exhibit reduced adipocyte size, and are protected from age and diet-induced glucose intolerance. There is also reduced Vegf and vascular permeability in FH1βKO fat, but diet-induced inflammation and fibrosis is unchanged. Adipocytes from FH1βKO mice have reduced glucose uptake due to decreased Glut1 and Glut4, which is mirrored in 3T3-L1 adipocytes with Hif1β knockdown. Hif1β knockdown cells also fail to respond appropriately to hypoxia with reduced cellular respiration and reduced mitochondrial gene expression. Some, but not all, of these effects are reproduced by Hif1α knockdown. Thus, Hif1β/Arnt regulates glucose uptake, mitochondrial gene expression, and vascular permeability to control adipose mass and function, providing a novel target for obesity therapy. PMID:21982709

  15. c-Jun DNAzymes inhibit myocardial inflammation, ROS generation, infarct size, and improve cardiac function after ischemia-reperfusion injury.

    Science.gov (United States)

    Luo, Xiao; Cai, Hong; Ni, Jun; Bhindi, Ravinay; Lowe, Harry C; Chesterman, Colin N; Khachigian, Levon M

    2009-11-01

    Coronary reperfusion has been the mainstay therapy for reduced infarct size after a heart attack. However, this intervention also results in myocardial injury by initiating a marked inflammatory reaction, and new treatments are keenly sought. The basic-region leucine zipper protein, c-Jun is poorly expressed in the normal myocardium and is induced within 24 hours after myocardial ischemia-reperfusion injury. Synthetic catalytic DNA molecules (DNAzymes) targeting c-Jun (Dz13) reduce infarct size in the area-at-risk (AAR) regardless of whether it is delivered intramyocardially at the initiation of ischemia or at the time of reperfusion. Dz13 attenuates neutrophil infiltration, c-Jun and ICAM-1 expression in vascular endothelium, cardiomyocyte apoptosis, and the generation of reactive oxygen species in the reperfused myocardium. It inhibits infiltration into the AAR of complement 3 (C3), C3a receptor (C3aR), membrane attack complex-1 (Mac-1), or matrix metalloproteinase-2 (MMP-2) positive inflammatory cells. Dz13 also improves cardiac function without influencing myocardial vascularity or fibrosis. These findings demonstrate the regulatory role of c-Jun in the pathogenesis of myocardial inflammation and infarction following ischemia-reperfusion injury, and inhibition of this process using catalytic DNA.

  16. Modular Small Diameter Vascular Grafts with Bioactive Functionalities.

    Directory of Open Access Journals (Sweden)

    Meik Neufurth

    Full Text Available We report the fabrication of a novel type of artificial small diameter blood vessels, termed biomimetic tissue-engineered blood vessels (bTEBV, with a modular composition. They are composed of a hydrogel scaffold consisting of two negatively charged natural polymers, alginate and a modified chitosan, N,O-carboxymethyl chitosan (N,O-CMC. Into this biologically inert scaffold two biofunctionally active biopolymers are embedded, inorganic polyphosphate (polyP and silica, as well as gelatin which exposes the cell recognition signal, Arg-Gly-Asp (RGD. These materials can be hardened by exposure to Ca(2+ through formation of Ca(2+ bridges between the polyanions, alginate, N,O-CMC, and polyP (alginate-Ca(2+-N,O-CMC-polyP. The bTEBV are formed by pressing the hydrogel through an extruder into a hardening solution, containing Ca(2+. In this universal scaffold of the bTEBV biomaterial, polycations such as poly(L-Lys, poly(D-Lys or a His/Gly-tagged RGD peptide (three RGD units were incorporated, which promote the adhesion of endothelial cells to the vessel surface. The mechanical properties of the biopolymer material (alginate-Ca(2+-N,O-CMC-polyP-silica revealed a hardness (elastic modulus of 475 kPa even after a short incubation period in CaCl2 solution. The material of the artificial vascular grafts (bTEBVs with an outer size 6 mm and 1.8 mm, and an inner diameter 4 mm and 0.8 mm, respectively turned out to be durable in 4-week pulsatile flow experiments at an alternating pressure between 25 and 100 mbar (18.7 and 75.0 mm Hg. The burst pressure of the larger (smaller vessels was 850 mbar (145 mbar. Incorporation of polycationic poly(L-Lys, poly(D-Lys, and especially the His/Gly-tagged RGD peptide, markedly increased the adhesion of human, umbilical vein/vascular endothelial cells, EA.HY926 cells, to the surface of the hydrogel. No significant effect of the polyP samples on the clotting of human plasma is measured. We propose that the metabolically

  17. Low Concentration of S100A8/9 Promotes Angiogenesis-Related Activity of Vascular Endothelial Cells: Bridges among Inflammation, Angiogenesis, and Tumorigenesis?

    Directory of Open Access Journals (Sweden)

    Changyou Li

    2012-01-01

    Full Text Available Previous studies showed that several members of the S100A family are involved in neovascularization and tumor development. This study checked whether low concentrations of S100A8 or S100A9 has any effect on the behaviour of vascular endothelial cells. A human umbilical vascular endothelial cell (HUVEC line was used to measure vascular endothelial cell bioactivity related to angiogenesis, such as cell proliferation, migration, and vessel formation. In the low concentration range up to 10 μg/mL, either each alone or in combination, S100A8 and S100A9 proteins promoted proliferation of HUVEC cells in a dose-dependent manner. The presence of both proteins in culture showed additive effects over each single protein. Both proteins enhanced HUVEC cells to migrate across the transwell membrane and to form tube-like structures on the Matrigel surface. When mixed in Matrigel and injected subcutaneously in Balb/c mice, both proteins increased vessel development in the gel plugs. Microarray assay of HUVEC cells treated with 10 μg/mL S100A8 revealed that ribosome pathway, pathogenic Escherichia coli infection pathway, apoptosis, and stress response genes were modulated by S100A8 treatment. We propose that S100A8 and S100A9 proteins from either infiltrating inflammatory cells or tumor cells play an important role in the interplay among inflammation, angiogenesis, and tumorigenesis.

  18. Vascular and Skeletal Muscle Function in Gulf War Veterans Illness

    Science.gov (United States)

    2017-07-01

    intraarterial IVUS, intraaterial flow, cardiopulmonary test, and bone density scan. As successful endpoint evaluation is dependent on the data from 70...cardiopulmonary exercise testing and other muscle functions, (3) expression of genes relevant to endothelial function and mitochondrial function in muscle... Exercise and Cardiopulmonary Stress Testing Schedule Visit 2 ( Exercise and cardiopulmonary stress tests) 3-28 Scheduling for Visit 1 continues to

  19. Smooth muscle architecture within cell-dense vascular tissues influences functional contractility.

    Science.gov (United States)

    Win, Zaw; Vrla, Geoffrey D; Steucke, Kerianne E; Sevcik, Emily N; Hald, Eric S; Alford, Patrick W

    2014-12-01

    The role of vascular smooth muscle architecture in the function of healthy and dysfunctional vessels is poorly understood. We aimed at determining the relationship between vascular smooth muscle architecture and contractile output using engineered vascular tissues. We utilized microcontact printing and a microfluidic cell seeding technique to provide three different initial seeding conditions, with the aim of influencing the cellular architecture within the tissue. Cells seeded in each condition formed confluent and aligned tissues but within the tissues, the cellular architecture varied. Tissues with a more elongated cellular architecture had significantly elevated basal stress and produced more contractile stress in response to endothelin-1 stimulation. We also found a correlation between the contractile phenotype marker expression and the cellular architecture, contrary to our previous findings in non-confluent tissues. Taken with previous results, these data suggest that within cell-dense vascular tissues, smooth muscle contractility is strongly influenced by cell and tissue architectures.

  20. Local vascular CO2 reactivity in the infant brain assessed by functional MRI

    DEFF Research Database (Denmark)

    Toft, P.B.; Leth, H; Lou, H.C.

    1995-01-01

    hyperventilated voluntarily, the vascular reactivity was homogeneously distributed predominantly over the grey matter. The experiments demonstrate that local impairment of vascular CO2 reactivity in the distressed infant brain can be detected by T2 sensitive gradient-echo MRI, which is also known as functional......The local cerebral vascular response to hyperventilation was investigated in five distressed, intubated infants by means of a T2 sensitive gradient-echo MRI technique at 1.5 T. In one preterm infant, the MR signal change during hyperventilation was sparse. In four term infants, the mean MR signal...... of the brain slice investigated decreased by 1.2-2.6% per kPa change in PCO2 as a reflection of decreased cerebral blood flow during hyperventilation. Pixel-wise analysis revealed absence of vascular response in the basal ganglia, the thalamus or in the occipital region. In two adult controls, who...

  1. Effects of cranberry juice consumption on vascular function in patients with coronary artery disease

    Science.gov (United States)

    Cranberry juice contains polyphenolic compounds that could improve endothelial function and reduce cardiovascular disease risk. The objective was to examine the effects of cranberry juice on vascular function in subjects with coronary artery disease. We completed an acute pilot study with no placebo...

  2. Effect of Roux-en-Y Bariatric Surgery on Lipoproteins, Insulin Resistance, and Systemic and Vascular Inflammation in Obesity and Diabetes

    Directory of Open Access Journals (Sweden)

    Rahul Yadav

    2017-11-01

    Full Text Available PurposeObesity is a major modifiable risk factor for cardiovascular disease. Bariatric surgery is considered to be the most effective treatment option for weight reduction in obese patients with and without type 2 diabetes (T2DM.ObjectiveTo evaluate changes in lipoproteins, insulin resistance, mediators of systemic and vascular inflammation, and endothelial dysfunction following Roux-en-Y bariatric surgery in obese patients with and without diabetes.Materials and methodsLipoproteins, insulin resistance, mediators of systemic and vascular inflammation, and endothelial dysfunction were measured in 37 obese patients with (n = 17 and without (n = 20 T2DM, before and 6 and 12 months after Roux-en-Y bariatric surgery. Two way between subject ANOVA was carried out to study the interaction between independent variables (time since surgery and presence of diabetes and all dependent variables.ResultsThere was a significant effect of time since surgery on (large effect size weight, body mass index (BMI, waist circumference, triglycerides (TG, small-dense LDL apolipoprotein B (sdLDL ApoB, HOMA-IR, CRP, MCP-1, ICAM-1, E-selectin, P-selectin, leptin, and adiponectin. BMI and waist circumference had the largest impact of time since surgery. The effect of time since surgery was noticed mostly in the first 6 months. Absence of diabetes led to a significantly greater reduction in total cholesterol, low-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol although the effect size was small to medium. There was a greater reduction in TG and HOMA-IR in patients with diabetes with a small effect size. No patients were lost to follow up.ConclusionLipoproteins, insulin resistance, mediators of systemic and vascular inflammation, and endothelial dysfunction improve mostly 6 months after bariatric surgery in obese patients with and without diabetes.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier: NCT02169518. https

  3. Doppler ultrasound findings correlate with tissue vascularity and inflammation in surgical pathology specimens from patients with small intestinal Crohn’s disease

    Science.gov (United States)

    2014-01-01

    Background Crohn’s disease (CD) is routinely evaluated using clinical symptoms, laboratory variables, and the CD activity index (CDAI). However, clinical parameters are often nonspecific and do not precisely reflect the actual activity of CD small-intestinal lesions. The purposes of this prospective study were to compare color Doppler ultrasound (US) findings with histological findings from surgically resected specimens and confirm the hypothesis that color Doppler US can distinguish tissue inflammation and fibrosis. Methods Among 1764 consecutive patients who underwent color Doppler US examinations, 10 patients with CD (12 small-intestinal CD lesions) who underwent US examinations before elective small-intestine resection were evaluated in the present study. Areas of thickened intestinal walls were evaluated in terms of blood flow using color Doppler US imaging. The blood flow was semiquantitatively classified as “hyper-flow” and “hypo-flow” according to the Limberg score. Resected lesions were macroscopically and histopathologically processed. Inflammatory cell infiltration, fibrosis and vascularity were evaluated by myeloperoxidase (granulocytes), CD163 (macrophages), CD79a (B cells), CD3 (T cells), Masson’s trichrome (fibrosis), and factor VIII staining (vascular walls). All histopathological images were entered into virtual slide equipment and quantified using a quantitative microscopy integrated system (TissueMorph™). Results There were no significant differences in disease features or laboratory findings between “hypo-flow” lesions (n = 4) and “hyper-flow” lesions (n = 8). Histopathologically, “hyper-flow” lesions showed significantly greater bowel wall vascularity (factor VIII) (p = 0.047) and inflammatory cell infiltration, including CD163 macrophages (p = 0.008), CD3 T cells, and CD79a B cells (p = 0.043), than did “hypo-flow” lesions. There was no apparent association between the blood flow and CDAI

  4. The effects of electronic cigarette aerosol exposure on inflammation and lung function in mice.

    Science.gov (United States)

    Larcombe, Alexander N; Janka, Maxine A; Mullins, Benjamin J; Berry, Luke J; Bredin, Arne; Franklin, Peter J

    2017-07-01

    Electronic cigarette usage is increasing worldwide, yet there is a paucity of information on the respiratory health effects of electronic cigarette aerosol exposure. This study aimed to assess whether exposure to electronic cigarette (e-cigarette) aerosol would alter lung function and pulmonary inflammation in mice and to compare the severity of any alterations with mice exposed to mainstream tobacco smoke. Female BALB/c mice were exposed for 8 wk to tobacco smoke, medical air (control), or one of four different types of e-cigarette aerosol. E-cigarette aerosols varied depending on nicotine content (0 or 12 mg/ml) and the main excipient (propylene glycol or glycerin). Twenty-four hours after the final exposure, we measured pulmonary inflammation, lung volume, lung mechanics, and responsiveness to methacholine. Mice exposed to tobacco cigarette smoke had increased pulmonary inflammation and responsiveness to methacholine compared with air controls. Mice exposed to e-cigarette aerosol did not have increased inflammation but did display decrements in parenchymal lung function at both functional residual capacity and high transrespiratory pressures. Mice exposed to glycerin-based e-cigarette aerosols were also hyperresponsive to methacholine regardless of the presence or absence of nicotine. This study shows, for the first time, that exposure to e-cigarette aerosol during adolescence and early adulthood is not harmless to the lungs and can result in significant impairments in lung function. Copyright © 2017 the American Physiological Society.

  5. Differential and synergistic effects of mechanical stimulation and growth factor presentation on vascular wall function

    Science.gov (United States)

    Liang, Mao-Shih; Koobatian, Maxwell T.; Lei, Pedro; Swartz, Daniel D.; Andreadis, Stelios T.

    2013-01-01

    We investigated the hypothesis that immobilizing TGF-β1 within fibrin hydrogels may act in synergy with cyclic mechanical stimulation to enhance the properties of vascular grafts. To this end, we engineered a fusion TGF-β1 protein that can covalently anchor to fibrin during polymerization upon the action of factor XIII. We also developed a 24-well based bioreactor in which vascular constructs can be mechanically stimulated by distending the silastic mandrel in the middle of each well. TGF-β1 was either conjugated to fibrin or supplied in the culture medium and the fibrin based constructs were cultured statically for a week followed by cyclic distention for another week. The tissues were examined for myogenic differentiation, vascular reactivity, mechanical properties and ECM content. Our results showed that some aspects of vascular function were differentially affected by growth factor presentation vs. pulsatile force application, while others were synergistically enhanced by both. Overall, this two-prong biomimetic approach improved ECM secretion, vascular reactivity and mechanical properties of vascular constructs. These findings may be applied in other tissue engineering applications such as cartilage, tendon or cardiac regeneration where growth factors TGF-β1 and mechano-stimulation play critical roles. PMID:23810080

  6. [Effect of tumor vascular invasion upon cardio-pulmonary exercise functions in patients with lung cancer].

    Science.gov (United States)

    Cao, Min; Li, Qi; Xie, Ru-ming; Sun, Gui-xin; Dong, Bo-tao; Ruan, Hong-yun; Wang, Zhi-ru; Zhang, Guo-hong

    2010-01-12

    To investigate the correlation between the tumor vascular invasion and the change of cardio-pulmonary exercise function in patients with lung cancer. The cardio-pulmonary exercise test was performed in 405 patients with lung cancer (293 with vascular invasion and 112 without). The peak load indices examined included maximal work power (measured value/predicted value, W%), maximal oxygen uptake per weight (VO(2)/kg), anaerobic threshold (AT), maximal oxygen pulse (measured value/predicted value, VO(2)/HR%), maximal minute ventilation (V(E)), maximal breath reserve (BR), maximal breath frequency (BF) and maximal tidal volume during expiration (VTex). (1) W%, VO(2)/kg, AT, VO(2)/HR% of patients with vascular invasion [(73 +/- 18)%, (17 +/- 5) ml * min(-1) * kg(-1), (51 +/- 14)%, (79 +/- 18)% respectively] decreased than those without vascular invasion [(86 +/- 20)%, (19 +/- 5) ml * min(-1) * kg(-1), (55 +/- 14)%, (88 +/- 20)% respectively, all P vascular invasion and its relationship with tumor, W%, VO(2)/HR% decreased in the groups of 1-, 2- and >or= 3-vessel invasion versus the control group (P or= 3-vessel invasion versus the control group (P or= 3-vessel invasion versus the control group (P or= 3-vessel invasion versus 1- and 2-vessel invasion (P or= 3-vessel invasion versus 1-vessel invasion (P or= 3-vessel invasion versus the control group and 1-vessel invasion (P vascular invasion. The main reason is the number of the invaded vessels.

  7. Regulation and function of bone morphogenetic protein signaling in colonic injury and inflammation.

    Science.gov (United States)

    Ji, Tuo; Takabayashi, Hidehiko; Mao, Maria; Han, Xu; Xue, Xiang; Brazil, Jennifer C; Eaton, Kathryn A; Shah, Yatrik M; Todisco, Andrea

    2017-01-01

    The bone morphogenetic proteins (BMPs) regulate gastrointestinal homeostasis. We investigated the expression of BMP-4 and the localization and function of BMP signaling during colonic injury and inflammation. Mice expressing the β-galactosidase (β-gal) gene under the control of a BMP-responsive element (BRE), BMP-4-β-gal/ mice, and animals generated by crossing villin-Cre mice to mice with floxed alleles of BMP receptor 1A (villin-Cre;Bmpr1a flox/flox ) were treated with dextran sodium sulfate (DSS) to induce colonic injury and inflammation. Expression of BMP-4, β-gal, BMPR1A, IL-8, α-smooth muscle actin, and phosphorylated Smad1, -5, and -8 was assessed by X-Gal staining, quantitative RT-PCR, and immunohistochemistry. Morphology of the colonic mucosa was examined by staining with hematoxylin and eosin. The effect of IFN-γ, TNF-α, IL-1β, and IL-6 on BMP-4 mRNA expression was investigated in human intestinal fibroblasts, whereas that of BMP-4 on IL-8 was assessed in human colonic organoids. BMP-4 was localized in α-smooth muscle actin-positive mesenchymal cells while the majority of BMP-generated signals targeted the epithelium. DSS caused injury and inflammation leading to reduced expression of BMP-4 and of BMPR1A mRNAs, and to decreased BMP signaling. Deletion of BMPR1A enhanced colonic inflammation and damage. Administration of anti-TNF-α antibodies to DSS-treated mice ameliorated colonic inflammation and increased the expression of BMP-4 and BMPR1A mRNAs. TNF-α and IL-1β inhibited both basal and IFN-γ-stimulated BMP-4 expression, whereas IL-6 had no effect. BMP-4 reduced TNF-α-stimulated IL-8 mRNA expressor IL-8 mRNA expression in the organoids. Inflammation and injury inhibit BMP-4 expression and signaling, leading to enhanced colonic damage and inflammation. These observations underscore the importance of BMP signaling in the regulation of intestinal inflammation and homeostasis. In this study we report a series of novel observations that

  8. Cannabidiol reduces lipopolysaccharide-induced vascular changes and inflammation in the mouse brain: an intravital microscopy study

    Directory of Open Access Journals (Sweden)

    Tolón Rosa M

    2011-01-01

    Full Text Available Abstract Background The phytocannabinoid cannabidiol (CBD exhibits antioxidant and antiinflammatory properties. The present study was designed to explore its effects in a mouse model of sepsis-related encephalitis by intravenous administration of lipopolysaccharide (LPS. Methods Vascular responses of pial vessels were analyzed by intravital microscopy and inflammatory parameters measured by qRT-PCR. Results CBD prevented LPS-induced arteriolar and venular vasodilation as well as leukocyte margination. In addition, CBD abolished LPS-induced increases in tumor necrosis factor-alpha and cyclooxygenase-2 expression as measured by quantitative real time PCR. The expression of the inducible-nitric oxide synthase was also reduced by CBD. Finally, preservation of Blood Brain Barrier integrity was also associated to the treatment with CBD. Conclusions These data highlight the antiinflammatory and vascular-stabilizing effects of CBD in endotoxic shock and suggest a possible beneficial effect of this natural cannabinoid.

  9. Effect of Buddleja officinalis on high-glucose-induced vascular inflammation in human umbilical vein endothelial cells.

    Science.gov (United States)

    Lee, Yun Jung; Kang, Dae Gill; Kim, Jin Sook; Lee, Ho Sub

    2008-06-01

    In this study, we aimed to investigate whether an aqueous extract of Buddleja officinalis (ABO) suppresses high-glucose-induced vascular inflammatory processes in the primary cultured human umbilical vein endothelial cells (HUVEC). The high-glucose-induced increase in expression of cell adhesion molecules (CAMs) such as intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial-selectin (E-selectin) was significantly attenuated by pretreatment with ABO in a dose-dependent manner. Enhanced cell adhesion caused by high glucose in co-cultured U937 and HUVEC was also blocked by pretreatment with ABO. Pretreatment with ABO also blocked formation of high-glucose-induced reactive oxygen species (ROS). In addition, ABO suppressed the transcriptional activity of NF-kappaB and IkappaB phosphorylation under high-glucose conditions. Pretreatment with N(G)-nitro-l-arginine methyl ester (L-NAME), an endothelial nitric oxide (NO) synthase inhibitor, attenuated the protective action of ABO on high-glucose-induced CAM expression, suggesting a potential role of NO signaling. The present data suggest that ABO could suppress high-glucose-induced vascular inflammatory processes, and ABO may be closely related with the inhibition of ROS and NF-kappaB activation in HUVEC.

  10. Acute Effects of Nitrate-Rich Beetroot Juice on Blood Pressure, Hemostasis and Vascular Inflammation Markers in Healthy Older Adults: A Randomized, Placebo-Controlled Crossover Study

    Directory of Open Access Journals (Sweden)

    Kyle Raubenheimer

    2017-11-01

    Full Text Available Aging is associated with a vasoconstrictive, pro-coagulant, and pro-inflammatory profile of arteries and a decline in the bioavailability of the endothelium-derived molecule nitric oxide. Dietary nitrate elicits vasodilatory, anti-coagulant and anti-inflammatory effects in younger individuals, but little is known about whether these benefits are evident in older adults. We investigated the effects of 140 mL of nitrate-rich (HI-NI; containing 12.9 mmol nitrate versus nitrate-depleted beetroot juice (LO-NI; containing ≤0.04 mmol nitrate on blood pressure, blood coagulation, vascular inflammation markers, plasma nitrate and nitrite before, and 3 h and 6 h after ingestion in healthy older adults (five males, seven females, mean age: 64 years, age range: 57–71 years in a randomized, placebo-controlled, crossover study. Plasma nitrate and nitrite increased 3 and 6 h after HI-NI ingestion (p < 0.05. Systolic, diastolic and mean arterial blood pressure decreased 3 h relative to baseline after HI-NI ingestion only (p < 0.05. The number of blood monocyte-platelet aggregates decreased 3 h after HI-NI intake (p < 0.05, indicating reduced platelet activation. The number of blood CD11b-expressing granulocytes decreased 3 h following HI-NI beetroot juice intake (p < 0.05, suggesting a shift toward an anti-adhesive granulocyte phenotype. Numbers of blood CD14++CD16+ intermediate monocyte subtypes slightly increased 6 h after HI-NI beetroot juice ingestion (p < 0.05, but the clinical implications of this response are currently unclear. These findings provide new evidence for the acute effects of nitrate-rich beetroot juice on circulating immune cells and platelets. Further long-term research is warranted to determine if these effects reduce the risk of developing hypertension and vascular inflammation with aging.

  11. Exposure to fluid shear stress modulates the ability of endothelial cells to recruit neutrophils in response to tumor necrosis factor-alpha: a basis for local variations in vascular sensitivity to inflammation.

    Science.gov (United States)

    Sheikh, Sajila; Rainger, G Ed; Gale, Zoe; Rahman, Mahbub; Nash, Gerard B

    2003-10-15

    Vascular endothelial cells are able to sense changes in the forces acting on them and respond, for instance, by modifying expression of a range of genes. However, there is little information on how such responses are integrated to modify homeostatic functions. We hypothesized that different shear stresses experienced in different regions of the circulation might influence endothelial sensitivity to inflammatory stimuli. We cultured human endothelial cells in tubes and exposed them for varying periods to shear stresses ranging from those typically found in postcapillary venules to those in arteries. When tumor necrosis factor-alpha was included in the flow cultures, we found startling differential effects of shear stress on the ability of endothelial cells to induce adhesion and migration of flowing neutrophils. Compared with static cultures, endothelial cells cultured at low shear stress (0.3 Pa) captured similar numbers of neutrophils but failed to induce their transendothelial migration. After exposure of endothelial cells to high shear stress (1.0 or 2.0 Pa), capture of neutrophils was largely ablated. The modification in response was detectable after 4 hours of exposure to flow but was much greater after 24 hours. From analysis of gene expression, loss of capture or migration was attributable to reduction in tumor necrosis factor-induced expression of selectins or CXC-chemokines, respectively. Thus, conditioning of endothelial cells by different flow environments may underlie variations in susceptibility to inflammation between different tissues or parts of the vascular tree.

  12. Polyphenolics from açaí ( Euterpe oleracea Mart.) and red muscadine grape (Vitis rotundifolia ) protect human umbilical vascular Endothelial cells (HUVEC) from glucose- and lipopolysaccharide (LPS)-induced inflammation and target microRNA-126.

    Science.gov (United States)

    Noratto, Giuliana D; Angel-Morales, Gabriela; Talcott, Stephen T; Mertens-Talcott, Susanne U

    2011-07-27

    Endothelial anti-inflammatory effects of açaí (Ac) and red muscadine grape (Gp) polyphenolics have not been extensively investigated. It was hypothesized that polyphenolics from Ac and Gp exert comparable protective effects in human vascular endothelial cells (HUVEC) upon inflammatory stress. Furthermore, this study investigated whether microRNAs relevant to endothelial function might be regulated by Ac and Gp. Results showed that Ac and Gp (5-20 mg gallic acid equivalent/L) protected HUVEC against glucose-induced oxidative stress and inflammation. Glucose-induced expression of interleukin-6 and -8 was down-regulated by Ac and Gp at mRNA and protein levels. Upon lipopolysaccharide (LPS; 1 μg/L)-induced inflammation, Ac and Gp inhibited gene expression of adhesion molecules and NF-κB activation to similar extents, although Gp was more effective in decreasing PECAM-1 and ICAM-1 protein. Of the screened microRNAs, only microRNA-126 expression was found to be modulated by Ac and Gp as the underlying mechanism to inhibit gene and protein expression of VCAM-1.

  13. Cannabidiol improves lung function and inflammation in mice submitted to LPS-induced acute lung injury.

    Science.gov (United States)

    Ribeiro, A; Almeida, V I; Costola-de-Souza, C; Ferraz-de-Paula, V; Pinheiro, M L; Vitoretti, L B; Gimenes-Junior, J A; Akamine, A T; Crippa, J A; Tavares-de-Lima, W; Palermo-Neto, J

    2015-02-01

    We have previously shown that the prophylactic treatment with cannabidiol (CBD) reduces inflammation in a model of acute lung injury (ALI). In this work we analyzed the effects of the therapeutic treatment with CBD in mice subjected to the model of lipopolysaccharide (LPS)-induced ALI on pulmonary mechanics and inflammation. CBD (20 and 80 mg/kg) was administered (i.p.) to mice 6 h after LPS-induced lung inflammation. One day (24 h) after the induction of inflammation the assessment of pulmonary mechanics and inflammation were analyzed. The results show that CBD decreased total lung resistance and elastance, leukocyte migration into the lungs, myeloperoxidase activity in the lung tissue, protein concentration and production of pro-inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and MIP-2) in the bronchoalveolar lavage supernatant. Thus, we conclude that CBD administered therapeutically, i.e. during an ongoing inflammatory process, has a potent anti-inflammatory effect and also improves the lung function in mice submitted to LPS-induced ALI. Therefore the present and previous data suggest that in the future cannabidiol might become a useful therapeutic tool for the attenuation and treatment of inflammatory lung diseases.

  14. Role of platelets in inflammation

    Directory of Open Access Journals (Sweden)

    Kadir Serkan Yalçın

    2012-09-01

    Full Text Available Inflammation, which is extremely useful process for humanbody is the response of living vascular tissues topathological phenomena that removes the pathogens andinitiates the healing procedure. Microorganisms, physicaltrauma, chemical, mechanical, irradiation, or thermal injury,ischemia and immune reactions are most commoncauses of this exceptionally important event for humanbody. Platelets are non-nucleated cells in blood that producedin bone marrow as derived from megakaryocytes.Apart from stop bleeding and achieving hemostasis thereare incredibly important roles of platelets in inflammation.Platelets contain important mediators for inflammationlike neutrophils or macrophages and can alter the courseof mechanism. In this article changing platelet function ininflammation and the effect of these functions to the processof inflammation will be discussed.Key words: Platelet, inflammation, cytokines

  15. Indoor Particles Affect Vascular Function in the Aged

    DEFF Research Database (Denmark)

    Bräuner, Elvira Vaclavik; Forchhammer, Lykke; Møller, Peter

    2008-01-01

    Rationale. Exposure to particulate matter is associated with risk of cardiovascular events, possibly through endothelial dysfunction and indoor air may be most important. Objective. We investigated effects of controlled exposure to indoor air particles on microvascular function as the primary end...... way of reducing the risk of cardiovascular disease....

  16. Construction of a fucoidan/laminin functional multilayer to direction vascular cell fate and promotion hemocompatibility

    Energy Technology Data Exchange (ETDEWEB)

    Ye, Changrong; Wang, Yan; Su, Hong; Yang, Ping; Huang, Nan [Key Laboratory of Advanced Materials Technology of Ministry of Education, Department of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China); Maitz, Manfred F. [Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Dresden 01069 (Germany); Zhao, Anshan [Key Laboratory of Advanced Materials Technology of Ministry of Education, Department of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China)

    2016-07-01

    Surface biofunctional modification of cardiovascular stents is a versatile approach to reduce the adverse effects after implantation. In this work, a novel multifunctional coating was fabricated by coimmobilization of the sulfated polysaccharide of brown algae fucoidan and laminin to biomimic the vascular intimal conditions in order to support rapid endothelialization, prevent restenosis and improve hemocompatibility. The surface properties of the coating such as hydrophilicity, bonding density of biomolecules and stability were evaluated and optimized. According to the biocompatibility tests, the fucoidan/laminin multilayer coated surface displayed less platelet adhesion with favorable anticoagulant property. In addition, the fucoidan/laminin complex showed function to selectively regulate vascular cells growth behavior. The proliferation of endothelial cells (ECs) on the fucoidan/laminin biofunctional coating was significantly promoted. For the smooth muscle cells (SMCs), inhibitory effects on cell adhesion and proliferation were observed. In conclusion, the fucoidan/laminin biofunctional coating was successfully fabricated with desirable anticoagulant and endothelialization properties which show a promising application in the vascular devices such as vascular stents or grafts surface modification. - Highlights: • Construction of fucoidan/laminin functional multilayer to biomimic the basement membrane of vascular • The fucoidan/laminin complex demonstrates anti-coagulation property. • The fucoidan/laminin complex can selectively regulate EC and SMC growth behavior to prevent restenosis.

  17. Effect of a previous pregnancy on vascular function in endothelial nitric oxide synthase 3 knockout mice.

    Science.gov (United States)

    Ghulmiyyah, Labib M; Tamayo, Esther; Clark, Shannon M; Hankins, Gary D V; Anderson, Garland D; Saade, George R; Longo, Monica

    2007-09-01

    Nitric oxide deficiency has been implicated in adverse pregnancy outcomes. Mice that lack endothelial nitric oxide synthase (NOS3) have abnormal in vitro vascular reactivity. Our objective was to assess the effect of a previous pregnancy on the abnormal vascular function of NOS3 knockout mice. Carotid arteries from pregnant NOS3 knockout (NOS3(-/-KO)) and wild-type control mice (NOS3(+/+WT)) from first and second pregnancy were obtained for in vitro vascular reactivity studies. Vascular responses to cumulative concentrations of the vasoconstrictors phenylephrine, serotonin, and thromboxane and the vasorelaxants acetylcholine, sodium nitroprusside, and isoproterenol were determined. In the first pregnancy, contractile responses were exaggerated in the knockout animals, compared with the wild-type animals. However, the second pregnancy in knockout animals was associated with normalization of responses to phenylephrine and serotonin and increased responses to the endothelium-independent relaxants. The vascular function of NOS3 knockout mice improves with subsequent pregnancy becoming comparable to wild-type animals.

  18. Hemoglobin-induced lung vascular oxidation, inflammation, and remodeling contribute to the progression of hypoxic pulmonary hypertension and is attenuated in rats with repeated-dose haptoglobin administration.

    Science.gov (United States)

    Irwin, David C; Baek, Jin Hyen; Hassell, Kathryn; Nuss, Rachelle; Eigenberger, Paul; Lisk, Christina; Loomis, Zoe; Maltzahn, Joanne; Stenmark, Kurt R; Nozik-Grayck, Eva; Buehler, Paul W

    2015-05-01

    Haptoglobin (Hp) is an approved treatment in Japan for trauma, burns, and massive transfusion-related hemolysis. Additional case reports suggest uses in other acute hemolytic events that lead to acute kidney injury. However, Hp's protective effects on the pulmonary vasculature have not been evaluated within the context of mitigating the consequences of chronic hemoglobin (Hb) exposure in the progression of pulmonary hypertension (PH) secondary to hemolytic diseases. This study was performed to assess the utility of chronic Hp therapy in a preclinical model of Hb and hypoxia-mediated PH. Rats were simultaneously exposed to chronic Hb infusion (35 mg per day) and hypobaric hypoxia for 5 weeks in the presence or absence of Hp treatment (90 mg/kg twice a week). Hp inhibited the Hb plus hypoxia-mediated nonheme iron accumulation in lung and heart tissue, pulmonary vascular inflammation and resistance, and right-ventricular hypertrophy, which suggests a positive impact on impeding the progression of PH. In addition, Hp therapy was associated with a reduction in critical mediators of PH, including lung adventitial macrophage population and endothelial ICAM-1 expression. By preventing Hb-mediated pathology, Hp infusions: (1) demonstrate a critical role for Hb in vascular remodeling associated with hypoxia and (2) suggest a novel therapy for chronic hemolysis-associated PH. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Vascular smooth muscle function of renal glomerular and interlobar arteries predicts renal damage in rats

    NARCIS (Netherlands)

    Vavrinec, Peter; Henning, Robert H.; Goris, Maaike; Vavrincova-Yaghi, Diana; Buikema, Hendrik; van Dokkum, Richard P. E.

    2012-01-01

    Vavrinec P, Henning RH, Goris M, Vavrincova-Yaghi D, Buikema H, van Dokkum RP. Vascular smooth muscle function of renal glomerular and interlobar arteries predicts renal damage in rats. Am J Physiol Renal Physiol 303: F1187-F1195, 2012. First published July 11, 2012;

  20. Variation in non-invasive measurements of vascular function in healthy volunteers during daytime.

    NARCIS (Netherlands)

    Avest, E. ter; Holewijn, S.; Stalenhoef, A.F.H.; Graaf, J. de

    2005-01-01

    Although it is often recommended to standardize the time of day when performing non-invasive measurements of vascular function, the exact influence of the time of day on the outcome of IMT (intima-media thickness), PWV (pulse wave velocity), AIX (augmentation index) and FMD (flow-mediated

  1. Does epicatechin contribute to the acute vascular function effects of dark chocolate? A randomized, crossover study

    NARCIS (Netherlands)

    Dower, James I.; Geleijnse, Marianne; Kroon, Paul A.; Philo, Mark; Mensink, Marco; Kromhout, Daan; Hollman, Peter C.H.

    2016-01-01

    Scope: Cocoa, rich in flavan-3-ols, improves vascular function, but the contribution of specific flavan-3-ols is unknown. We compared the effects of pure epicatechin, a major cocoa flavan-3-ol, and chocolate. Methods and results: In a randomized crossover study, twenty healthy men (40-80 years)

  2. Progressive Vascular Functional and Structural Damage in a Bronchopulmonary Dysplasia Model in Preterm Rabbits Exposed to Hyperoxia.

    Science.gov (United States)

    Jiménez, Julio; Richter, Jute; Nagatomo, Taro; Salaets, Thomas; Quarck, Rozenn; Wagennar, Allard; Wang, Hongmei; Vanoirbeek, Jeroen; Deprest, Jan; Toelen, Jaan

    2016-10-24

    Bronchopulmonary dysplasia (BPD) is caused by preterm neonatal lung injury and results in oxygen dependency and pulmonary hypertension. Current clinical management fails to reduce the incidence of BPD, which calls for novel therapies. Fetal rabbits have a lung development that mimics humans and can be used as a translational model to test novel treatment options. In preterm rabbits, exposure to hyperoxia leads to parenchymal changes, yet vascular damage has not been studied in this model. In this study we document the early functional and structural changes of the lung vasculature in preterm rabbits that are induced by hyperoxia after birth. Pulmonary artery Doppler measurements, micro-CT barium angiograms and media thickness of peripheral pulmonary arteries were affected after seven days of hyperoxia when compared to controls. The parenchyma was also affected both at the functional and structural level. Lung function testing showed higher tissue resistance and elastance, with a decreased lung compliance and lung capacity. Histologically hyperoxia leads to fewer and larger alveoli with thicker walls, less developed distal airways and more inflammation than normoxia. In conclusion, we show that the rabbit model develops pulmonary hypertension and developmental lung arrest after preterm lung injury, which parallel the early changes in human BPD. Thus it enables the testing of pharmaceutical agents that target the cardiovascular compartment of the lung for further translation towards the clinic.

  3. Inhibition of Secretory Phospholipase A(2) in Patients with Acute Coronary Syndromes: Rationale and Design of the Vascular Inflammation Suppression to Treat Acute Coronary Syndrome for 16 Weeks (VISTA-16) Trial

    NARCIS (Netherlands)

    Nicholls, Stephen J.; Cavender, Matthew A.; Kastelein, John J. P.; Schwartz, Gregory; Waters, David D.; Rosenson, Robert S.; Bash, Dianna; Hislop, Colin

    2012-01-01

    Background The action of secretory phospholipase A(2) (sPLA(2)) on lipoproteins may render them more susceptible to oxidation, thereby promoting vascular inflammation and increasing cardiovascular risk. Patients with acute coronary syndrome face a high risk of early, recurrent cardiovascular events

  4. Saccharin induced liver inflammation in mice by altering the gut microbiota and its metabolic functions.

    Science.gov (United States)

    Bian, Xiaoming; Tu, Pengcheng; Chi, Liang; Gao, Bei; Ru, Hongyu; Lu, Kun

    2017-09-01

    Maintaining the balance of the gut microbiota and its metabolic functions is vital for human health, however, this balance can be disrupted by various external factors including food additives. A range of food and beverages are sweetened by saccharin, which is generally considered to be safe despite controversial debates. However, recent studies indicated that saccharin perturbed the gut microbiota. Inflammation is frequently associated with disruptions of the gut microbiota. The aim of this study is to investigate the relationship between host inflammation and perturbed gut microbiome by saccharin. C57BL/6J male mice were treated with saccharin in drinking water for six months. Q-PCR was used to detect inflammatory markers in mouse liver, while 16S rRNA gene sequencing and metabolomics were used to reveal changes of the gut microbiota and its metabolomic profiles. Elevated expression of pro-inflammatory iNOS and TNF-α in liver indicated that saccharin induced inflammation in mice. The altered gut bacterial genera, enriched orthologs of pathogen-associated molecular patterns, such as LPS and bacterial toxins, in concert with increased pro-inflammatory metabolites suggested that the saccharin-induced liver inflammation could be associated with the perturbation of the gut microbiota and its metabolic functions. Copyright © 2017. Published by Elsevier Ltd.

  5. Comparison between Alzheimer's disease and subcortical vascular dementia: attentional cortex study in functional magnetic resonance imaging.

    Science.gov (United States)

    Li, C; Zheng, J; Wang, J; Gui, L

    2011-01-01

    Blood oxygen level dependent functional magnetic resonance imaging (fMRI) and the Stroop test were used to assess attentional cortex activation in patients with Alzheimer's disease, subcortical vascular dementia, and normal control subjects. Patients with Alzheimer's disease and subcortical vascular dementia demonstrated similar locations of cortical activation, including the bilateral middle and inferior frontal gyri, anterior cingulate and inferior parietal lobule in response to Stroop colour word stimuli. This activation was distinctly decreased in patients with dementia compared with normal control subjects. Different regions of the brain were activated in patients with Alzheimer's disease and subcortical vascular dementia compared with normal controls. fMRI is a useful tool for the study of dementia in humans and has some potential diagnostic value. Further studies with larger numbers of participants are required.

  6. Clinical Correlates of Hachinski Ischemic Score and Vascular Factors in Cognitive Function of Elderly

    Directory of Open Access Journals (Sweden)

    Youn Ho Kim

    2014-01-01

    Full Text Available The aim of this study is to investigate the relationship between Hachinski ischemic score (HIS and vascular factors as well as between HIS and the cognitive function in elderly community. Demographic characteristics, such as sex, age, education, history of drinking and smoking, family history of dementia and stroke, diabetes mellitus, hypertension, hyperlipidemia, cardiovascular disease, stroke, and dementia, were surveyed. Neurological examination was administered to every subject and HIS was checked by a neurologist. From a total of 392 participants aged 65 and over in a rural community, 348 completed the survey and were finally enrolled. Among the vascular factors, history of hypertension (P=0.008, history of stroke (P<0.001, family history of dementia (P=0.01, and history of cardiac diseases (P=0.012 showed a significant relationship with HIS. In the cognitive function tests, both Korean version of the Mini-Mental State Examination and the Clinical Dementia Rating (Global and Sum of Boxes had a significant relationship with HIS. Our study suggested HIS may have an association with some vascular factors and cognitive scales in community dwelling elderly. In this study, the HIS seemed to contribute to the evaluation of the quantity of vascular factors and to the prediction of status of cognitive function.

  7. Bioengineering functional human aortic vascular smooth-muscle strips in vitro.

    Science.gov (United States)

    Hecker, Louise; Khait, Luda; Welsh, Michael J; Birla, Ravi

    2008-07-01

    The contraction and relaxation of VSM (vascular smooth muscle) are responsible for the maintenance of vascular tone, which is a major determinant of blood pressure. However, the molecular events leading to the contraction and relaxation of VSM are poorly understood. The development of three-dimensional bioengineered tissues provides an opportunity to investigate the molecular events controlling vascular tone in vitro. In the present study we used fibrin-gel casting to bioengineer functional VSM strips from primary human aortic VSM cells. Our bioengineered VSM strips are functionally similar to VSM in vivo and remained viable in culture for up to 5 weeks. VSM strips demonstrate spontaneous basal tone and can generate an active force (contraction) of up to 85.2 microN on stimulation with phenylephrine. Bioengineered VSM strips exhibited Ca(2+)-dependent contraction and calcium-independent relaxation. The development of functional bioengineered VSM tissue provides a new in vitro model system that can be used to investigate the molecular events controlling vascular tone.

  8. Vascular function and endothelin-1: tipping the balance between vasodilation and vasoconstriction.

    Science.gov (United States)

    Nishiyama, Steven K; Zhao, Jia; Wray, D Walter; Richardson, Russell S

    2017-02-01

    Endothelin-1 (ET-1), a potent vasoconstrictor secreted by vascular endothelial cells, has been implicated in the pathophysiology of numerous cardiovascular diseases, yet the direct impact of ET-1 on vascular function remains unclear. Therefore, in seven young (23 ± 1 yr) healthy subjects, we investigated the effect of an intra-arterial infusion of ET-1 on reactive hyperemia (RH) and flow-mediated dilation (FMD) in the popliteal artery following 5 min of suprasystolic cuff occlusion. ET-1 infusion significantly attenuated basal leg blood flow (control: 62 ± 4 ml/min, ET-1: 47 ± 9 ml/min), RH [area-under-curve (AUC); control: 162 ± 15 ml, ET-1: 104 ± 16 ml], and peak RH (control: 572 ± 51 ml/min, ET-1: 412 ± 32 ml/min) (P tipping the balance between vasodilation and vasoconstriction, in favor of the latter.NEW & NOTEWORTHY Endothelin-1 (ET-1) is recognized as the body's most potent endogenous vasoconstrictor, but the impact of this peptide on vascular function is not well understood. The present study revealed that the intra-arterial administration of ET-1 impaired both microvascular and conduit vessel function of the leg in young, healthy, humans. Studies employing vascular testing in patient cohorts that experience a disease-related increase in ET-1 should thus exercise caution, as ET-1 clearly impairs vascular function. Copyright © 2017 the American Physiological Society.

  9. Frailty and poor functional status are common in arterial vascular surgical patients and affect postoperative outcomes.

    Science.gov (United States)

    Partridge, Judith S L; Fuller, Matthew; Harari, Danielle; Taylor, Peter R; Martin, Finbarr C; Dhesi, Jugdeep K

    2015-06-01

    Increasing numbers of older people are undergoing emergency and elective arterial vascular procedures. Many older patients are frail which is a recognised predictor of adverse postoperative outcomes in other surgical specialties. This study in older patients undergoing arterial vascular surgery examined; the prevalence of preoperative frailty; the clinical feasibility of preoperatively measuring frailty and functional status; the association between these characteristics and adverse postoperative outcome. Prospective observational study in patients aged over 60 years undergoing elective and emergency arterial vascular surgery. Baseline measures of frailty (Edmonton Frail Scale), functional status (gait velocity, timed up and go, hand grip strength) and cognitive function (Montreal Cognitive Assessment) were obtained preoperatively. The primary outcome measure Length of Stay (LOS) and secondary outcome measures of postoperative morbidity (medical and surgical complications), functional status and postoperative in-hospital mortality were recorded. 125 patients were recruited. Frailty was common in this older surgical population (52% EFS score of ≥ 6.5) with high frailty scores observed (mean EFS 6.6, SD 3.05) and poor functional status (60% had TUG > 15 s, 45% had gait velocity of 6.5) was univariately associated with longer LOS (≥ 12 days), composite measures of postoperative infections, postoperative medical complications and adverse functional outcomes. EFS ≥ 6.5 was predictive of LOS ≥ 12 days, adjusted for age (AUC 0.660, CI 0.541-0.779, p = 0.010). This association between EFS ≥ 6.5 and LOS ≥ 12 days was strengthened with the addition of MoCA < 24 (AUC 0.695, CI 0.584-0.806, p = 0.002). Patients aged over 60 years admitted for arterial vascular surgery were frail, had impaired functional status and were cognitively impaired. This combination of preoperative characteristics was predictive of longer hospital length of stay and associated with adverse

  10. A proinflammatory diet is associated with systemic inflammation and reduced kidney function in elderly adults.

    Science.gov (United States)

    Xu, Hong; Sjögren, Per; Ärnlöv, Johan; Banerjee, Tanushree; Cederholm, Tommy; Risérus, Ulf; Lindholm, Bengt; Lind, Lars; Carrero, Juan Jesús

    2015-04-01

    Diet can affect kidney health through its effects on inflammation. We tested whether the Adapted Dietary Inflammatory Index (ADII) is associated with kidney function and whether effects of diet on chronic low-grade inflammation explain this association. This was an observational analysis in 1942 elderly community-dwelling participants aged 70-71 y from 2 independent cohorts: the Uppsala Longitudinal Study of Adult Men (n = 1097 men) and the Prospective Investigation of Vasculature in Uppsala Seniors (n = 845 men and women). The ADII was calculated from 7-d food records, combining putatively proinflammatory and anti-inflammatory effects of nutrients, vitamins, and trace elements. The ADII was validated against serum C-reactive protein (CRP) concentrations. The estimated glomerular filtration rate (eGFR) was assessed from serum cystatin C (cys) and creatinine (crea). Associations between the ADII and eGFR were investigated, and CRP was considered to be a mediator. In adjusted analysis, a 1-SD higher ADII was associated with higher CRP (β: 6%; 95% CI: 1%, 10%; P = 0.01) and lower eGFR [Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)cys: -2.1%; 95% CI: -3.2%, -1.1%; CKD-EPIcys+crea: -1.8%; 95% CI: -2.7%, -0.9%; both P kidney function, 15% and 17% (for CKD-EPIcys+crea and CKD-EPIcys equations, respectively) were explained/mediated by serum CRP. Findings were similar when each cohort was analyzed separately. A proinflammatory diet was associated with systemic inflammation as well as with reduced kidney function in a combined analysis of 2 community-based cohorts of elderly individuals. Our results also suggest systemic inflammation to be one potential pathway through which this dietary pattern is linked to kidney function. © 2015 American Society for Nutrition.

  11. The effect of age on the relationship between cardiac and vascular function.

    Science.gov (United States)

    Houghton, David; Jones, Thomas W; Cassidy, Sophie; Siervo, Mario; MacGowan, Guy A; Trenell, Michael I; Jakovljevic, Djordje G

    2016-01-01

    Age-related changes in cardiac and vascular function are associated with increased risk of cardiovascular mortality and morbidity. The aim of the present study was to define the effect of age on the relationship between cardiac and vascular function. Haemodynamic and gas exchange measurements were performed at rest and peak exercise in healthy individuals. Augmentation index was measured at rest. Cardiac power output, a measure of overall cardiac function, was calculated as the product of cardiac output and mean arterial blood pressure. Augmentation index was significantly higher in older than younger participants (27.7 ± 10.1 vs. 2.5 ± 10.1%, Pconsumption (22.5 ± 5.2 vs. 41.2 ± 8.4 ml/kg/min, Pfunction due to increased stroke volume. Vascular function is a strong predictor of overall cardiac function in older but in not younger people. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  12. Role of vascular inflammation in coronary artery disease: potential of anti-inflammatory drugs in the prevention of atherothrombosis. Inflammation and anti-inflammatory drugs in coronary artery disease.

    Science.gov (United States)

    Moreira, Daniel Medeiros; da Silva, Roberto Leo; Vieira, Jefferson Luís; Fattah, Tammuz; Lueneberg, Maria Emilia; Gottschall, Carlos Antonio Mascia

    2015-02-01

    Coronary artery disease (CAD) and acute myocardial infarction (AMI) are inflammatory pathologies, involving interleukins (ILs), such as IL-1β, IL-6 and tumor necrosis factor (TNF)-α, and acute phase proteins production, such as for C reactive protein (CRP). The process begins with retention of low-density lipoprotein (LDL) and its oxidation inside the intima, with the formation of the "foam cells." Toll-like receptors and inflamassomes participate in atherosclerosis formation, as well as in the activation of the complement system. In addition to innate immunity, adaptive immunity is also associated with atherosclerosis through antigen-presenting cells, T and B lymphocytes. AMI also increases the expression of some ILs and promotes macrophage and lymphocyte accumulation. Reperfusion increases the expression of anti-inflammatory ILs (such as IL-10) and generates oxygen free radicals. Although CAD and AMI are inflammatory disorders, the only drugs with anti-inflammatory effect so far widely used in ischemic heart disease are aspirin and statins. Some immunomodulatory or immunosuppressive promising therapies, such as cyclosporine and colchicine, may have benefits in CAD. Methotrexate also has potential cardioprotective anti-inflammatory effects, through increased adenosine levels. The TETHYS trial (The Effects of mETHotrexate Therapy on ST Segment Elevation MYocardial InfarctionS trial) will evaluate low-dose methotrexate in ST elevation AMI. The CIRT (Cardiovascular Inflammation Reduction Trial), in turn, will evaluate low-dose methotrexate in patients with a high prevalence of subclinical vascular inflammation. The CANTOS (The Canakinumab Antiinflammatory Thrombosis Outcomes Study) will evaluate canakinumab in patients with CAD and persistently elevated CRP. The blockage of other potential targets, such as the IL-6 receptor, CC2 chemokine receptor and CD20, could bring benefits in CAD.

  13. Pregnancy-induced alterations of vascular function in mouse mesenteric and uterine arteries.

    Science.gov (United States)

    Cooke, Christy-Lynn M; Davidge, Sandra T

    2003-03-01

    Normal pregnancy involves dramatic changes to maternal vascular function, while abnormal vascular adaptations may contribute to pregnancy-associated diseases such as preeclampsia. Many genetic mouse models have recently emerged to study vascular pathologies of pregnancy. However, vascular adaptations to pregnancy in normal mice are not fully understood. Thus, we studied changes in vascular reactivity during normal mouse pregnancy. We hypothesized that pregnant mice will have enhanced endothelial-dependent vasodilation compared with nonpregnant mice, via an enhancement of the nitric oxide synthase (NOS) prostaglandin H synthase (PGHS), and other endothelial-derived hyperpolarizing pathways. Late pregnant (Day 17-18) C57BL/6J mice (n = 10) were compared with nonpregnant mice (n = 7). Uterine and mesenteric arteries were mounted on a wire myograph system and assessed for endothelium-dependent (methacholine) and -independent (sodium nitroprusside; SNP) relaxation responses. Endothelial-dependent relaxation was enhanced in pregnant uterine and mesenteric arteries, which was blunted after the addition of inhibitors of the PGHS or NOS pathways. In nonpregnant mice, these pathways had no effect in modulating relaxation in uterine arteries, whereas vasodilation in mesenteric arteries was reduced only by NOS inhibition. Both uterine and mesenteric vessels had nonnitric oxide- and nonprostaglandin-mediated relaxation, but this relaxation was not enhanced during pregnancy. Endothelial-independent relaxation was also enhanced in pregnant uterine but not mesenteric arteries. Our data indicate that uterine and mesenteric arteries from pregnant mice have enhanced vasodilation. Understanding vascular adaptations to normal mouse pregnancy is crucial for interpreting changes that may occur in genetic mouse models.

  14. Coronary endothelial function and vascular smooth muscle proliferation are programmed by early-gestation dexamethasone exposure in sheep

    OpenAIRE

    Volk, Kenneth A.; Roghair, Robert D.; Jung, Felicia; Scholz, Thomas D.; Lamb, Fred S.; Segar, Jeffrey L.

    2010-01-01

    Exposure of the early-gestation ovine fetus to exogenous glucocorticoids induces changes in postnatal cardiovascular physiology. We sought to characterize coronary artery vascular function in this model by elucidating the contribution of nitric oxide and reactive oxygen species to altered coronary vascular reactivity and examining the proliferative potential of coronary artery vascular smooth muscle cells. Dexamethasone (dex, 0.28 mg·kg−1·day−1 for 48 h) was administered to pregnant ewes at 2...

  15. Left ventricular systolic function is associated with sympathetic nervous activity and markers of inflammation in cirrhosis.

    Science.gov (United States)

    Yotti, Raquel; Ripoll, Cristina; Benito, Yolanda; Catalina, Maria Vega; Elízaga, Jaime; Rincón, Diego; Fernández-Avilés, Francisco; Bermejo, Javier; Bañares, Rafael

    2017-06-01

    An accurate evaluation of cardiac function in patients with cirrhosis remains a challenge. We used robust echocardiographic indices to characterize left ventricular (LV) systolic function and its relationship to activation of the sympathetic nervous system and inflammation in 59 patients with cirrhosis and 59 age-matched controls. Additionally, in 11 patients we withdrew beta-blockers and diuretics and used phenylephrine and albumin infusion to evaluate the response to acute afterload and preload changes (interventional substudy). Measures of systolic LV function such as the ejection intraventricular pressure difference (EIVPD) and the systolic strain rate were higher in patients with cirrhosis than in controls (median [1st-3rd quartile], 4.0 [3.1-5.1] versus 2.9 [2.4-3.6] mm Hg and -1.3 [-1.6 to -1.1] versus -1.2 [-1.6 to -1.1)] s-1 , respectively; P function (P function is enhanced in cirrhosis due to augmented adrenergic tone and modulated by treatment with beta-blockers; acute afterload stress induces a deeper impairment of systolic function in patients with more advanced degrees of vasodilatation and inflammation; these changes in LV function related to cirrhosis can be assessed using robust echocardiographic methods. (Hepatology 2017;65:2019-2030). © 2017 by the American Association for the Study of Liver Diseases.

  16. Human primary adipocytes exhibit immune cell function: adipocytes prime inflammation independent of macrophages.

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    Kees Meijer

    Full Text Available BACKGROUND: Obesity promotes inflammation in adipose tissue (AT and this is implicated in pathophysiological complications such as insulin resistance, type 2 diabetes and cardiovascular disease. Although based on the classical hypothesis, necrotic AT adipocytes (ATA in obese state activate AT macrophages (ATM that then lead to a sustained chronic inflammation in AT, the link between human adipocytes and the source of inflammation in AT has not been in-depth and systematically studied. So we decided as a new hypothesis to investigate human primary adipocytes alone to see whether they are able to prime inflammation in AT. METHODS AND RESULTS: Using mRNA expression, human preadipocytes and adipocytes express the cytokines/chemokines and their receptors, MHC II molecule genes and 14 acute phase reactants including C-reactive protein. Using multiplex ELISA revealed the expression of 50 cytokine/chemokine proteins by human adipocytes. Upon lipopolysaccharide stimulation, most of these adipocyte-associated cytokines/chemokines and immune cell modulating receptors were up-regulated and a few down-regulated such as (ICAM-1, VCAM-1, MCP-1, IP-10, IL-6, IL-8, TNF-α and TNF-β highly up-regulated and IL-2, IL-7, IL-10, IL-13 and VEGF down-regulated. In migration assay, human adipocyte-derived chemokines attracted significantly more CD4+ T cells than controls and the number of migrated CD4+ cells was doubled after treating the adipocytes with LPS. Neutralizing MCP-1 effect produced by adipocytes reduced CD4+ migration by approximately 30%. CONCLUSION: Human adipocytes express many cytokines/chemokines that are biologically functional. They are able to induce inflammation and activate CD4+ cells independent of macrophages. This suggests that the primary event in the sequence leading to chronic inflammation in AT is metabolic dysfunction in adipocytes, followed by production of immunological mediators by these adipocytes, which is then exacerbated by

  17. Endothelial CD47 promotes vascular endothelial-cadherin tyrosine phosphorylation and participates in T cell recruitment at sites of inflammation in vivo.

    Science.gov (United States)

    Azcutia, Veronica; Stefanidakis, Michael; Tsuboi, Naotake; Mayadas, Tanya; Croce, Kevin J; Fukuda, Daiju; Aikawa, Masanori; Newton, Gail; Luscinskas, Francis W

    2012-09-01

    At sites of inflammation, endothelial adhesion molecules bind leukocytes and transmit signals required for transendothelial migration (TEM). We previously reported that adhesive interactions between endothelial cell CD47 and leukocyte signal regulatory protein γ (SIRPγ) regulate human T cell TEM. The role of endothelial CD47 in T cell TEM in vivo, however, has not been explored. In this study, CD47⁻/⁻ mice showed reduced recruitment of blood T cells as well as neutrophils and monocytes in a dermal air pouch model of TNF-α-induced inflammation. Reconstitution of CD47⁻/⁻ mice with wild-type bone marrow cells did not restore leukocyte recruitment to the air pouch, indicating a role for endothelial CD47. The defect in leukocyte TEM in the CD47⁻/⁻ endothelium was corroborated by intravital microscopy of inflamed cremaster muscle microcirculation in bone marrow chimera mice. In an in vitro human system, CD47 on both HUVEC and T cells was required for TEM. Although previous studies showed CD47-dependent signaling required G(αi)-coupled pathways, this was not the case for endothelial CD47 because pertussis toxin, which inactivates G(αi), had no inhibitory effect, whereas G(αi) was required by the T cell for TEM. We next investigated the endothelial CD47-dependent signaling events that accompany leukocyte TEM. Ab-induced cross-linking of CD47 revealed robust actin cytoskeleton reorganization and Src- and Pyk-2-kinase dependent tyrosine phosphorylation of the vascular endothelial-cadherin cytoplasmic tail. This signaling was pertussis toxin insensitive, suggesting that endothelial CD47 signaling is independent of G(αi). These findings suggest that engagement of endothelial CD47 by its ligands triggers outside-in signals in endothelium that facilitate leukocyte TEM.

  18. Ultrasound and dynamic functional imaging in vascular cognitive impairment and Alzheimer's disease.

    Science.gov (United States)

    Malojcic, Branko; Giannakopoulos, Panteleimon; Sorond, Farzaneh A; Azevedo, Elsa; Diomedi, Marina; Oblak, Janja Pretnar; Carraro, Nicola; Boban, Marina; Olah, Laszlo; Schreiber, Stephan J; Pavlovic, Aleksandra; Garami, Zsolt; Bornstein, Nantan M; Rosengarten, Bernhard

    2017-02-09

    The vascular contributions to neurodegeneration and neuroinflammation may be assessed by magnetic resonance imaging (MRI) and ultrasonography (US). This review summarises the methodology for these widely available, safe and relatively low cost tools and analyses recent work highlighting their potential utility as biomarkers for differentiating subtypes of cognitive impairment and dementia, tracking disease progression and evaluating response to treatment in various neurocognitive disorders. At the 9th International Congress on Vascular Dementia (Ljubljana, Slovenia, October 2015) a writing group of experts was formed to review the evidence on the utility of US and arterial spin labelling (ASL) as neurophysiological markers of normal ageing, vascular cognitive impairment (VCI) and Alzheimer's disease (AD). Original articles, systematic literature reviews, guidelines and expert opinions published until September 2016 were critically analysed to summarise existing evidence, indicate gaps in current knowledge and, when appropriate, suggest standards of use for the most widely used US and ASL applications. Cerebral hypoperfusion has been linked to cognitive decline either as a risk or an aggravating factor. Hypoperfusion as a consequence of microangiopathy, macroangiopathy or cardiac dysfunction can promote or accelerate neurodegeneration, blood-brain barrier disruption and neuroinflammation. US can evaluate the cerebrovascular tree for pathological structure and functional changes contributing to cerebral hypoperfusion. Microvascular pathology and hypoperfusion at the level of capillaries and small arterioles can also be assessed by ASL, an MRI signal. Despite increasing evidence supporting the utility of these methods in detection of microvascular pathology, cerebral hypoperfusion, neurovascular unit dysfunction and, most importantly, disease progression, incomplete standardisation and missing validated cut-off values limit their use in daily routine. US and ASL are

  19. Inflammation and the Peritoneal Membrane: Causes and Impact on Structure and Function during Peritoneal Dialysis

    Directory of Open Access Journals (Sweden)

    Gilberto Baroni

    2012-01-01

    Full Text Available Peritoneal dialysis therapy has increased in popularity since the end of the 1970s. This method provides a patient survival rate equivalent to hemodialysis and better preservation of residual renal function. However, technique failure by peritonitis, and ultrafiltration failure, which is a multifactorial complication that can affect up to 40% of patients after 3 years of therapy. Encapsulant peritoneal sclerosis is an extreme and potentially fatal manifestation. Causes of inflammation in peritoneal dialysis range from traditional factors to those related to chronic kidney disease per se, as well as from the peritoneal dialysis treatment, including the peritoneal dialysis catheter, dialysis solution, and infectious peritonitis. Peritoneal inflammation generated causes significant structural alterations including: thickening and cubic transformation of mesothelial cells, fibrin deposition, fibrous capsule formation, perivascular bleeding, and interstitial fibrosis. Structural alterations of the peritoneal membrane described above result in clinical and functional changes. One of these clinical manifestations is ultrafiltration failure and can occur in up to 30% of patients on PD after five years of treatment. An understanding of the mechanisms involved in peritoneal inflammation is fundamental to improve patient survival and provide a better quality of life.

  20. Structure and Functions of Blood Vessels and Vascular Niches in Bone

    Directory of Open Access Journals (Sweden)

    Saravana K. Ramasamy

    2017-01-01

    Full Text Available Bone provides nurturing microenvironments for an array of cell types that coordinate important physiological functions of the skeleton, such as energy metabolism, mineral homeostasis, osteogenesis, and haematopoiesis. Endothelial cells form an intricate network of blood vessels that organises and sustains various microenvironments in bone. The recent identification of heterogeneity in the bone vasculature supports the existence of multiple vascular niches within the bone marrow compartment. A unique combination of cells and factors defining a particular microenvironment, supply regulatory signals to mediate a specific function. This review discusses recent developments in our understanding of vascular niches in bone that play a critical role in regulating the behaviour of multipotent haematopoietic and mesenchymal stem cells during development and homeostasis.

  1. Single passive leg movement-induced hyperemia: a simple vascular function assessment without a chronotropic response.

    Science.gov (United States)

    Venturelli, Massimo; Layec, Gwenael; Trinity, Joel; Hart, Corey R; Broxterman, Ryan M; Richardson, Russell S

    2017-01-01

    Passive leg movement (PLM)-induced hyperemia is a novel approach to assess vascular function, with a potential clinical role. However, in some instances, the varying chronotropic response induced by PLM has been proposed to be a potentially confounding factor. Therefore, we simplified and modified the PLM model to require just a single PLM (sPLM), an approach that may evoke a peripheral hemodynamic response, allowing a vascular function assessment, but at the same time minimizing central responses. To both characterize and assess the utility of sPLM, in 12 healthy subjects, we measured heart rate (HR), stroke volume, cardiac output (CO), mean arterial pressure (MAP), leg blood flow (LBF), and calculated leg vascular conductance (LVC) during both standard PLM, consisting of passive knee flexion and extension performed at 1 Hz for 60 s, and sPLM, consisting of only a single passive knee flexion and extension over 1 s. During PLM, MAP transiently decreased (5 ± 1 mmHg), whereas both HR and CO increased from baseline (6.0 ± 1.1 beats/min, and 0.8 ± 0.01 l/min, respectively). Following sPLM, MAP fell similarly (5 ± 2 mmHg; P = 0.8), but neither HR nor CO responses were identifiable. The peak LBF and LVC response was similar for PLM (993 ± 189 ml/min; 11.9 ± 1.5 ml·min(-1)·mmHg(-1), respectively) and sPLM (878 ± 119 ml/min; 10.9 ± 1.6 ml·min(-1)·mmHg(-1), respectively). Thus sPLM represents a variant of the PLM approach to assess vascular function that is more easily performed and evokes a peripheral stimulus that induces a significant hyperemia, but does not generate a potentially confounding, chronotropic response, which may make sPLM more useful clinically. Using the single passive leg movement (PLM) technique, a variant of the vascular function assessment PLM, we have identified a novel peripheral vascular assessment method that is more easily performed than PLM, which, by not evoking potentially confounding central hemodynamic responses, may be more

  2. The CRC orthologue from Pisum sativum shows conserved functions in carpel morphogenesis and vascular development

    Science.gov (United States)

    Fourquin, Chloé; Primo, Amparo; Martínez-Fernández, Irene; Huet-Trujillo, Estefanía; Ferrándiz, Cristina

    2014-01-01

    Background and Aims CRABS CLAW (CRC) is a member of the YABBY family of transcription factors involved in carpel morphogenesis, floral determinacy and nectary specification in arabidopsis. CRC orthologues have been functionally characterized across angiosperms, revealing additional roles in leaf vascular development and carpel identity specification in Poaceae. These studies support an ancestral role of CRC orthologues in carpel development, while roles in vascular development and nectary specification appear to be derived. This study aimed to expand research on CRC functional conservation to the legume family in order to better understand the evolutionary history of CRC orthologues in angiosperms. Methods CRC orthologues from Pisum sativum and Medicago truncatula were identified. RNA in situ hybridization experiments determined the corresponding expression patterns throughout flower development. The phenotypic effects of reduced CRC activity were investigated in P. sativum using virus-induced gene silencing. Key Results CRC orthologues from P. sativum and M. truncatula showed similar expression patterns, mainly restricted to carpels and nectaries. However, these expression patterns differed from those of other core eudicots, most importantly in a lack of abaxial expression in the carpel and in atypical expression associated with the medial vein of the ovary. CRC downregulation in pea caused defects in carpel fusion and style/stigma development, both typically associated with CRC function in eudicots, but also affected vascular development in the carpel. Conclusions The data support the conserved roles of CRC orthologues in carpel fusion, style/stigma development and nectary development. In addition, an intriguing new aspect of CRC function in legumes was the unexpected role in vascular development, which could be shared by other species from widely diverged clades within the angiosperms, suggesting that this role could be ancestral rather than derived, as so far

  3. Indoor particles affect vascular function in the aged: an air filtration-based intervention study.

    OpenAIRE

    Brauner, Elvira Vaclavik; Forchhammer, Lykke; Moller, Peter; Barregard, Lars; Gunnarsen, Lars; Afshari, Alireza; Wahlin, Peter; Glasius, Marianne; Dragsted, Lars Ove; Basu, Samar; Raaschou-Nielsen, Ole; Loft, Steffen

    2008-01-01

    Comment in:Am J Respir Crit Care Med. 2008 Feb 15;177(4):366-367. RATIONALE: Exposure to particulate matter is associated with risk of cardiovascular events, possibly through endothelial dysfunction, and indoor air may be most important. OBJECTIVES: We investigated effects of controlled exposure to indoor air particles on microvascular function (MVF) as the primary endpoint and biomarkers of inflammation and oxidative stress as secondary endpoints in a healthy elderly population. METHODS: ...

  4. Antioxidants and vascular health.

    Science.gov (United States)

    Bielli, Alessandra; Scioli, Maria Giovanna; Mazzaglia, Donatella; Doldo, Elena; Orlandi, Augusto

    2015-12-15

    Oxygen free radicals and other reactive oxygen species (ROS) are common products of normal aerobic cellular metabolism, but high levels of ROS lead to oxidative stress and cellular damage. Increased production of ROS favors vascular dysfunction, inducing altered vascular permeability and inflammation, accompanied by the loss of vascular modulatory function, the imbalance between vasorelaxation and vasoconstriction, and the aberrant expression of inflammatory adhesion molecules. Inflammatory stimuli promote oxidative stress generated from the increased activity of mitochondrial nicotinamide adenine dinucleotide phosphate oxidase, particularly of the Nox4 isoform, with the consequent impairment of mitochondrial β-oxidation. Vascular dysfunction due to the increase in Nox4 activity and ROS overproduction leads to the progression of cardiovascular diseases, diabetes, inflammatory bowel disease, and neurological disorders. Considerable research into the development of effective antioxidant therapies using natural derivatives or new synthetic molecules has been conducted. Antioxidants may prevent cellular damage by reducing ROS overproduction or interfering in reactions that involve ROS. Vitamin E and ascorbic acid are well known as natural antioxidants that counteract lipid peroxidative damage by scavenging oxygen-derived free radicals, thus restoring vascular function. Recently, preliminary studies on natural antioxidants such as goji berries, thymus, rosemary, green tea ginseng, and garlic have been conducted for their efficacy in preventing vascular damage. N-acetyl-cysteine and propionyl-L-carnitine are synthetic compounds that regulate ROS production by replacing endogenous antioxidants in both endothelial and smooth muscle cells. In this review, we consider the molecular mechanisms underlying the generation of oxidative stress-induced vascular dysfunction as well as the beneficial effects of antioxidant therapies.

  5. Does epicatechin contribute to the acute vascular function effects of dark chocolate? A randomized, crossover study.

    Science.gov (United States)

    Dower, James I; Geleijnse, Johanna M; Kroon, Paul A; Philo, Mark; Mensink, Marco; Kromhout, Daan; Hollman, Peter C H

    2016-11-01

    Cocoa, rich in flavan-3-ols, improves vascular function, but the contribution of specific flavan-3-ols is unknown. We compared the effects of pure epicatechin, a major cocoa flavan-3-ol, and chocolate. In a randomized crossover study, twenty healthy men (40-80 years) were supplemented with: (1) 70g dark chocolate (150 mg epicatechin) with placebo capsules; (2) pure epicatechin capsules (2 × 50 mg epicatechin) with 75g white chocolate; and (3) placebo capsules with 75 g white chocolate (0 mg epicatechin). Vascular function (flow-mediated dilation (FMD) and augmentation index (AIx)) were measured before and 2 hours after interventions. Epicatechin metabolites time-profiles were measured in blood to calculate the bioavailability. Pure epicatechin did not significantly improve FMD (+0.75%; p = 0.10) or AIx (-2.2%; p = 0.23) compared to placebo. Dark chocolate significantly improved FMD (+0.96%; p = 0.04) and AIx (-4.6%; p = 0.02). Differences in improvements in FMD (+ 0.21%; p = 0.65) or Aix (-2.4%; p = 0.20) between pure epicatechin and dark chocolate were not significant. The bioavailability of epicatechin did not differ between pure epicatechin and dark chocolate (p = 0.14). Despite differences in epicatechin dose, improvements in vascular function after pure epicatechin and chocolate were similar and the bioavailability did not differ, suggesting a role for epicatechin. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. RGD peptide and graphene oxide co-functionalized PLGA nanofiber scaffolds for vascular tissue engineering.

    Science.gov (United States)

    Shin, Yong Cheol; Kim, Jeonghyo; Kim, Sung Eun; Song, Su-Jin; Hong, Suck Won; Oh, Jin-Woo; Lee, Jaebeom; Park, Jong-Chul; Hyon, Suong-Hyu; Han, Dong-Wook

    2017-06-01

    In recent years, much research has been suggested and examined for the development of tissue engineering scaffolds to promote cellular behaviors. In our study, RGD peptide and graphene oxide (GO) co-functionalized poly(lactide-co-glycolide, PLGA) (RGD-GO-PLGA) nanofiber mats were fabricated via electrospinning, and their physicochemical and thermal properties were characterized to explore their potential as biofunctional scaffolds for vascular tissue engineering. Scanning electron microscopy images revealed that the RGD-GO-PLGA nanofiber mats were readily fabricated and composed of random-oriented electrospun nanofibers with average diameter of 558 nm. The successful co-functionalization of RGD peptide and GO into the PLGA nanofibers was confirmed by Fourier-transform infrared spectroscopic analysis. Moreover, the surface hydrophilicity of the nanofiber mats was markedly increased by co-functionalizing with RGD peptide and GO. It was found that the mats were thermally stable under the cell culture condition. Furthermore, the initial attachment and proliferation of primarily cultured vascular smooth muscle cells (VSMCs) on the RGD-GO-PLGA nanofiber mats were evaluated. It was revealed that the RGD-GO-PLGA nanofiber mats can effectively promote the growth of VSMCs. In conclusion, our findings suggest that the RGD-GO-PLGA nanofiber mats can be promising candidates for tissue engineering scaffolds effective for the regeneration of vascular smooth muscle.

  7. Exercise and Vascular Function in Child Obesity: A Meta-Analysis.

    Science.gov (United States)

    Dias, Katrin A; Green, Daniel J; Ingul, Charlotte B; Pavey, Toby G; Coombes, Jeff S

    2015-09-01

    Conduit artery flow-mediated dilation (FMD) is a noninvasive index of preclinical atherosclerosis in humans. Exercise interventions can improve FMD in both healthy and clinical populations. This systematic review and meta-analysis aimed to summarize the effect of exercise training on FMD in overweight and obese children and adolescents as well as investigate the role of cardiorespiratory fitness (peak oxygen consumption [Vo2peak]) on effects observed. PubMed, Medline, Embase, and Cinahl databases were searched from the earliest available date to February 2015. Studies of children and/or adolescents who were overweight or obese were included. Standardized data extraction forms were used for patient and intervention characteristics, control/comparator groups, and key outcomes. Procedural quality of the studies was assessed using a modified version of the Physiotherapy Evidence Base Database scale. A meta-analysis involving 219 participants compared the mean difference of pre- versus postintervention vascular function (FMD) and Vo2peak between an exercise training intervention and a control condition. There was a significantly greater improvement in FMD (mean difference 1.54%, P exercise training compared with controls. Given the diversity of exercise prescriptions, participant characteristics, and FMD measurement protocols, varying FMD effect size was noted between trials. Exercise training improves vascular function in overweight and obese children, as indicated by enhanced FMD. Further research is required to establish the optimum exercise program for maintenance of healthy vascular function in this at-risk pediatric population. Copyright © 2015 by the American Academy of Pediatrics.

  8. Relationship between serum levels of triglycerides and vascular inflammation, measured as COX-2, in arteries from diabetic patients: a translational study

    Science.gov (United States)

    2013-01-01

    Background Inflammation is a common feature in the majority of cardiovascular disease, including Diabetes Mellitus (DM). Levels of pro-inflammatory markers have been found in increasing levels in serum from diabetic patients (DP). Moreover, levels of Cyclooxygenase-2 (COX-2) are increased in coronary arteries from DP. Methods Through a cross-sectional design, patients who underwent CABG were recruited. Vascular smooth muscle cells (VSMC) were cultured and COX-2 was measured by western blot. Biochemical and clinical data were collected from the medical record and by blood testing. COX-2 expression was analyzed in internal mammary artery cross-sections by confocal microscopy. Eventually, PGI2 and PGE2 were assessed from VSMC conditioned media by ELISA. Results Only a high glucose concentration, but a physiological concentration of triglycerides exposure of cultured human VSMC derived from non-diabetic patients increased COX-2 expression .Diabetic patients showed increasing serum levels of glucose, Hb1ac and triglycerides. The bivariate analysis of the variables showed that triglycerides was positively correlated with the expression of COX-2 in internal mammary arteries from patients (r2 = 0.214, P < 0.04). Conclusions We conclude that is not the glucose blood levels but the triglicerydes leves what increases the expression of COX-2 in arteries from DP. PMID:23642086

  9. System A activity and vascular function in the placental-specific Igf2 knockout mouse.

    Science.gov (United States)

    Kusinski, L C; Dilworth, M R; Baker, P N; Sibley, C P; Wareing, M; Glazier, J D

    2011-11-01

    Deletion of the placental-specific P0 transcript of the insulin-like growth factor gene (Igf2) reduces placental growth from early pregnancy onwards. In Igf2 P0 knockout fetuses (P0), maternofetal flux of (14)C-methylaminoisobutyric acid ((14)C-MeAIB) mediated by system A amino acid transporter activity is increased at embryonic day 16 (E16), but this stimulation is not sustained, and by E19, fetal growth restriction (FGR) ensues. Here, we investigated whether upregulated (14)C-MeAIB transfer does occur concomitantly with a change in System A amino acid transporter activity and whether altered uteroplacental vascular function contributes to the FGR. We tested the hypothesis that FGR in P0 mice is attributable to altered nutrient transport rather than aberrant uteroplacental vascular function. Plasma membrane vesicles were isolated from placentas of P0 and wild-type (WT) fetuses at E16 and E19. System A amino acid transporter activity was measured as sodium-dependent (14)C-MeAIB uptake over 60s. Wire myography was performed on uterine artery branches supplying P0 or WT implantation sites and agonist-induced constriction and dilation measured. Sodium-dependent uptake of (14)C-MeAIB (at 60s) was significantly (P vascular reactivity was comparable between groups. System A activity in the maternal-facing plasma membrane of syncytiotrophoblast layer II underpins the adaptations observed in the transplacental MeAIB flux of P0 mice. Unaltered uterine artery vascular function suggests that the FGR phenotype of P0 fetuses is primarily due to deficient placental nutrient exchange capacity. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Chronic binge alcohol exposure during pregnancy impairs rat maternal uterine vascular function.

    Science.gov (United States)

    Subramanian, Kaviarasan; Naik, Vishal D; Sathishkumar, Kunju; Yallampalli, Chandrashekar; Saade, George R; Hankins, Gary D; Ramadoss, Jayanth

    2014-07-01

    Alcohol exposure during pregnancy results in an array of structural and functional abnormalities called fetal alcohol spectrum disorders (FASD). Alcohol dysregulates the exquisite coordination and regulation of gestational adaptations at the level of the uterine vasculature. We herein hypothesized that chronic binge-like alcohol results in uterine vascular dysfunction and impairs maternal uterine artery reactivity to vasoconstrictors and dilators. We utilized a once-daily binge alcohol (4.5 g/kg body weight) exposure paradigm (gestational day 7 to 17) in a pregnant rat model system and investigated primary uterine artery function in response to vasoconstrictors and vasodilators utilizing wire myography. Alcohol (peak blood alcohol concentration, 216 mg/dl) produced uterine vascular dysfunction. Alcohol did not produce altered uterine vascular reactivity to α1 adrenergic agonist phenylephrine or the prostanoid thromboxane. However, alcohol specifically impaired acetylcholine (ACh)-mediated uterine artery vasodilation but exogenous endothelium-independent vasodilators like sodium nitroprusside exhibited no alcohol effect; ACh significantly decreased vessel relaxation (p = 0.003; ↓pD2 [negative log molar ACh concentration producing the half maximum response], -7.004 ± 0.215 vs. -6.310 ± 0.208; EMax [maximal ACh response], 92% vs. 75%). We conclude that moderate alcohol exposure impairs uterine vascular function in pregnant mothers. Alcohol specifically impairs agonist-induced uterine artery vasodilation. In summary, the maternal uterine compartment may play a significant role in the pathogenesis of FASD. Thus, the mechanistic targets of alcohol at the level of both the mother and the fetus need to be considered in order to develop effective therapeutic treatment strategies for FASD. Copyright © 2014 by the Research Society on Alcoholism.

  11. Effects of Salmeterol and Fluticasone Propionate Combination versus Fluticasone Propionate on Airway Function and Eosinophilic Inflammation in Mild Asthma

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    Makoto Hoshino

    2009-01-01

    Conclusions: These findings suggest that SFC is more useful than FP in mild asthma cases. The clinical benefit of SFC provides evidence that IOS and induced sputum allows for the detection of changes in airway function and inflammation.

  12. Effects of real and simulated weightlessness on the cardiac and peripheral vascular functions of humans: A review

    Directory of Open Access Journals (Sweden)

    Hui Zhu

    2015-10-01

    Full Text Available Weightlessness is an extreme environment that can cause a series of adaptive changes in the human body. Findings from real and simulated weightlessness indicate altered cardiovascular functions, such as reduction in left ventricular (LV mass, cardiac arrhythmia, reduced vascular tone and so on. These alterations induced by weightlessness are detrimental to the health, safety and working performance of the astronauts, therefore it is important to study the effects of weightlessness on the cardiovascular functions of humans. The cardiovascular functional alterations caused by weightlessness (including long-term spaceflight and simulated weightlessness are briefly reviewed in terms of the cardiac and peripheral vascular functions. The alterations include: changes of shape and mass of the heart; cardiac function alterations; the cardiac arrhythmia; lower body vascular regulation and upper body vascular regulation. A series of conclusions are reported, some of which are analyzed, and a few potential directions are presented.

  13. Vascular structural and functional changes: their association with causality in hypertension: models, remodeling and relevance.

    Science.gov (United States)

    Lee, Robert Mkw; Dickhout, Jeffrey G; Sandow, Shaun L

    2017-04-01

    Essential hypertension is a complex multifactorial disease process that involves the interaction of multiple genes at various loci throughout the genome, and the influence of environmental factors such as diet and lifestyle, to ultimately determine long-term arterial pressure. These factors converge with physiological signaling pathways to regulate the set-point of long-term blood pressure. In hypertension, structural changes in arteries occur and show differences within and between vascular beds, between species, models and sexes. Such changes can also reflect the development of hypertension, and the levels of circulating humoral and vasoactive compounds. The role of perivascular adipose tissue in the modulation of vascular structure under various disease states such as hypertension, obesity and metabolic syndrome is an emerging area of research, and is likely to contribute to the heterogeneity described in this review. Diversity in structure and related function is the norm, with morphological changes being causative in some beds and states, and in others, a consequence of hypertension. Specific animal models of hypertension have advantages and limitations, each with factors influencing the relevance of the model to the human hypertensive state/s. However, understanding the fundamental properties of artery function and how these relate to signalling mechanisms in real (intact) tissues is key for translating isolated cell and model data to have an impact and relevance in human disease etiology. Indeed, the ultimate aim of developing new treatments to correct vascular dysfunction requires understanding and recognition of the limitations of the methodologies used.

  14. A review about biomarkers for the investigation of vascular function and impairment in diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Derosa G

    2016-11-01

    Full Text Available Giuseppe Derosa,1 Pamela Maffioli2 1Centre of Diabetes and Metabolic Diseases, Department of Internal Medicine and Therapeutics, University of Pavia and Fondazione IRCCS Policlinico S. Matteo, 2School in Experimental Medicine, University of Pavia, Pavia, Italy Abstract: The aim of this review was to analyze the main biomarkers of vascular function and impairment in patients with type 2 diabetes. Medline, SCOPUS, Web of Science, and Google Scholar databases were searched. We concluded that proatherogenic adhesion molecules (soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, and soluble E selectin and inflammatory cytokines (high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-α were elevated in type 2 diabetes mellitus. Their increased expression and release contribute to the accelerated atherogenesis typical of these patients. For these reasons, the early identification of high levels of these biomarkers will help to establish new strategies to reduce cardiovascular complications. Keywords: biomarkers, vascular function, type 2 diabetes mellitus

  15. VEGF production and signaling in Müller glia are critical to modulating vascular function and neuronal integrity in diabetic retinopathy and hypoxic retinal vascular diseases.

    Science.gov (United States)

    Le, Yun-Zheng

    2017-10-01

    Müller glia (MG) are major retinal supporting cells that participate in retinal metabolism, function, maintenance, and protection. During the pathogenesis of diabetic retinopathy (DR), a neurovascular disease and a leading cause of blindness, MG modulate vascular function and neuronal integrity by regulating the production of angiogenic and trophic factors. In this article, I will (1) briefly summarize our work on delineating the role and mechanism of MG-modulated vascular function through the production of vascular endothelial growth factor (VEGF) and on investigating VEGF signaling-mediated MG viability and neural protection in diabetic animal models, (2) explore the relationship among VEGF and neurotrophins in protecting Müller cells in in vitro models of diabetes and hypoxia and its potential implication to neuroprotection in DR and hypoxic retinal diseases, and (3) discuss the relevance of our work to the effectiveness and safety of long-term anti-VEGF therapies, a widely used strategy to combat DR, diabetic macular edema, neovascular age-related macular degeneration, retinopathy of prematurity, and other hypoxic retinal vascular disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. A review about biomarkers for the investigation of vascular function and impairment in diabetes mellitus.

    Science.gov (United States)

    Derosa, Giuseppe; Maffioli, Pamela

    2016-01-01

    The aim of this review was to analyze the main biomarkers of vascular function and impairment in patients with type 2 diabetes. Medline, SCOPUS, Web of Science, and Google Scholar databases were searched. We concluded that proatherogenic adhesion molecules (soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, and soluble E selectin) and inflammatory cytokines (high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-α) were elevated in type 2 diabetes mellitus. Their increased expression and release contribute to the accelerated atherogenesis typical of these patients. For these reasons, the early identification of high levels of these biomarkers will help to establish new strategies to reduce cardiovascular complications.

  17. Mechanisms of Vascular Aging: New Perspectives

    Science.gov (United States)

    Kaley, Gabor; de Cabo, Rafael; Sonntag, William E.; Csiszar, Anna

    2010-01-01

    This review focuses on molecular, cellular, and functional changes that occur in the vasculature during aging; explores the links between mitochondrial oxidative stress, inflammation, and development of vascular disease in the elderly patients; and provides a landscape of molecular mechanisms involved in cellular oxidative stress resistance, which could be targeted for the prevention or amelioration of unsuccessful vascular aging. Practical interventions for prevention of age-associated vascular dysfunction and disease in old age are considered here based on emerging knowledge of the effects of anti-inflammatory treatments, regular exercise, dietary interventions, and caloric restriction mimetics. PMID:20576649

  18. Enhancement of 26S proteasome functionality connects oxidative stress and vascular endothelial inflammatory response in diabetes mellitus.

    Science.gov (United States)

    Liu, Hongtao; Yu, Shujie; Xu, Wenjia; Xu, Jian

    2012-09-01

    Although the connection of oxidative stress and inflammation has been long recognized in diabetes mellitus, the underlying mechanisms are not fully elucidated. This study defined the role of 26S proteasomes in promoting vascular inflammatory response in early diabetes mellitus. The 26S proteasome functionality, markers of autophagy, and unfolded protein response were assessed in (1) cultured 26S proteasome reporter cells and endothelial cells challenged with high glucose, (2) transgenic reporter (Ub(G76V)-green fluorescence protein) and wild-type (C57BL/6J) mice rendered diabetic, and (3) genetically diabetic (Akita and OVE26) mice. In glucose-challenged cells, and also in aortic, renal, and retinal tissues from diabetic mice, enhanced 26S proteasome functionality was observed, evidenced by augmentation of proteasome (chymotrypsin-like) activities and reduction in 26S proteasome reporter proteins, accompanied by increased nitrotyrosine-containing proteins. Also, whereas inhibitor of the nuclear factor κ-light-chain-enhancer of activated B cells α proteins were decreased, an increase was found in nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) nucleus translocation, which enhanced the NF-κB-mediated proinflammatory response, without affecting markers of autophagy or unfolded protein response. Importantly, the alterations were abolished by MG132 administration, small interfering RNA knockdown of PA700 (proteasome activator protein complex), or superoxide scavenging in vivo. Early hyperglycemia enhances 26S proteasome functionality, not autophagy or unfolded protein response, through peroxynitrite/superoxide-mediated PA700-dependent proteasomal activation, which elevates NF- ĸB-mediated endothelial inflammatory response in early diabetes mellitus.

  19. Circulating miRNAs in Pediatric Pulmonary Hypertension Show Promise as Biomarkers of Vascular Function

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    Vitaly O. Kheyfets

    2017-01-01

    Full Text Available Background/Objectives. The objective of this study was to evaluate the utility of circulating miRNAs as biomarkers of vascular function in pediatric pulmonary hypertension. Method. Fourteen pediatric pulmonary arterial hypertension patients underwent simultaneous right heart catheterization (RHC and blood biochemical analysis. Univariate and stepwise multivariate linear regression was used to identify and correlate measures of reactive and resistive afterload with circulating miRNA levels. Furthermore, circulating miRNA candidates that classified patients according to a 20% decrease in resistive afterload in response to oxygen (O2 or inhaled nitric oxide (iNO were identified using receiver-operating curves. Results. Thirty-two circulating miRNAs correlated with the pulmonary vascular resistance index (PVRi, pulmonary arterial distensibility, and PVRi decrease in response to O2 and/or iNO. Multivariate models, combining the predictive capability of multiple promising miRNA candidates, revealed a good correlation with resistive (r=0.97, P2−tailed<0.0001 and reactive (r=0.86, P2−tailed<0.005 afterloads. Bland-Altman plots showed that 95% of the differences between multivariate models and RHC would fall within 0.13 (mmHg−min/Lm2 and 0.0085/mmHg for resistive and reactive afterloads, respectively. Circulating miR-663 proved to be a good classifier for vascular responsiveness to acute O2 and iNO challenges. Conclusion. This study suggests that circulating miRNAs may be biomarkers to phenotype vascular function in pediatric PAH.

  20. Vascular function and risk factors in children with epilepsy: associations with sodium valproate and carbamazepine.

    Science.gov (United States)

    Keenan, Ngaire; Sadlier, Lynette G; Wiltshire, Esko

    2014-08-01

    To investigate biochemical cardiovascular risk factors and vascular endothelial function and structure in children with epilepsy on antiepileptic drugs (AEDs), particularly sodium valproate (VPA) and carbamazepine (CBZ). Individuals with epilepsy have increased risk factors for vascular disease, particularly lipid abnormalities and elevated total plasma homocyst(e)ine (tHcy). AED induced B-vitamin deficiencies have been suggested to contribute to this risk. Vitamin B supplementation has consequently been recommended for children on AEDs. Early vascular endothelial dysfunction and atherosclerosis are detectable by measuring flow-mediated dilation (FMD) and intima-media thickness (IMT). Thirty children with epilepsy on AEDs (13.3±2.3 years, 14 male) and 30 controls (13.9±2.9 years, 14 male) were recruited. Fasting tHcy, folate, pyridoxal-5-phosphate (PLP), vitamin B12, glucose and lipids were measured. Vascular function and structure were assessed using FMD (brachial artery) and IMT (carotid/aortic arteries). No differences were found between children with epilepsy and controls for tHcy, folate, PLP, lipids, FMD, carotid or aortic IMT. Vitamin B12 levels were elevated and glucose reduced in children treated with VPA. Elevated total cholesterol, cholesterol/HDL ratio and triglycerides occurred in children treated with CBZ. Aortic IMT correlated with weight (r=0.75, pvalproate or carbamazepine. We were also unable to confirm previous reports of tHcy abnormalities in this group. This may be due to higher B-vitamin intake, which compensates for loss of vitamins induced by this AED therapy. Vitamin supplementation in children with epilepsy on valproate and carbamazepine is not required in populations with adequate dietary intake of B vitamins. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Effect of paricalcitol on endothelial function and inflammation in type 2 diabetes and chronic kidney disease.

    Science.gov (United States)

    Thethi, Tina K; Bajwa, Muhammad A; Ghanim, Husam; Jo, Chanhee; Weir, Monica; Goldfine, Allison B; Umpierrez, Guillermo; Desouza, Cyrus; Dandona, Paresh; Fang-Hollingsworth, Ying; Raghavan, Vasudevan; Fonseca, Vivian A

    2015-04-01

    Patients with type 2 diabetes (T2DM) and chronic kidney disease (CKD) have impaired endothelial function. Vitamin D and its analogs may play a role in regulation of endothelial function and inflammation. We studied effects of paricalcitol compared to placebo on endothelial function and markers of inflammation and oxidative stress in patients with T2DM and CKD. A double blind, randomized, placebo-controlled trial was conducted in 60 patients with T2DM and stage 3 or 4 CKD. Paricalcitol 1 mcg or placebo was administered orally once daily for three months. Brachial artery flow mediated dilatation (FMD), nitroglycerine mediated dilation (NMD), and plasma concentrations of inflammatory cytokines, tumor necrosis factor -α and interleukin-6, highly-sensitive C-reactive protein; endothelial surface proteins, intercellular adhesion molecule -1 and monocyte chemo attractant protein-1, and plasma glucose, insulin, free fatty acids, and urinary isoprostane were measured at baseline and end of three months. 27 patients in the paricalcitol group and 28 patients in the control group completed the study, though analysis of FMD at both time points was possible in 23 patients in each group. There was no significant difference in the change in FMD, NMD or the biomarkers examined after paricalcitol or placebo treatment. Treatment with paricalcitol at this dose and duration did not affect brachial artery FMD or biomarkers of inflammation and oxidative stress. The lack of significance may be due to the fact that the study patients had advanced CKD and that effects of paricalcitol are not additive to the effects of glycemic, lipid and anti-hypertensive therapies. Published by Elsevier Inc.

  2. Resistance training reduces inflammation and fatigue and improves physical function in older breast cancer survivors.

    Science.gov (United States)

    Serra, Monica C; Ryan, Alice S; Ortmeyer, Heidi K; Addison, Odessa; Goldberg, Andrew P

    2017-08-21

    Resistance training (RT) reduces fatigue and improves physical function and quality of life (QOL) in breast cancer survivors (BCS). This may be related to reductions in systemic and tissue-specific inflammation. This pilot study examines the hypothesis that RT induces changes in systemic and tissue-specific inflammation that contribute to improvements in physical and behavioral function in postmenopausal BCS. Eleven BCS (60 ± 2 years old, body mass index 30 ± 1 kg/m, mean ± SEM) underwent assessments of fatigue (Piper Fatigue Scale), physical function, QOL (SF-36), glucose and lipid metabolism, and systemic, skeletal muscle, and adipose tissue inflammation (n = 9) before and after 16 weeks of moderate-intensity whole-body RT. Muscle strength improved by 25% to 30% (P < 0.01), QOL by 10% (P = 0.04), chair stand time by 15% (P = 0.01), 6-minute walk distance by 4% (P = 0.03), and fatigue decreased by 58% (P < 0.01), fasting insulin by 18% (P = 0.04), and diastolic and systolic blood pressure by approximately 5% (P = 0.04) after RT. BCS with the worst fatigue and QOL demonstrated the greatest improvements (absolute change vs baseline: fatigue: r = -0.95, P < 0.01; QOL: r = -0.82, P < 0.01). RT was associated with an approximately 25% to 35% relative reduction in plasma and adipose tissue protein levels of proinflammatory interleukin (IL)-6sR, serum amyloid A, and tumor necrosis factor-α, and 75% relative increase in muscle pro-proliferative, angiogenic IL-8 protein content by 75% (all P < 0.05). BCS with the highest baseline proinflammatory cytokine levels had the greatest absolute reductions, and the change in muscle IL-8 correlated directly with improvements in leg press strength (r = 0.53, P = 0.04). These preliminary results suggest that a progressive RT program effectively lowers plasma and tissue-specific inflammation, and that these changes are associated with reductions in fatigue

  3. Relationship between adipokines, inflammation, and vascular reactivity in lean controls and obese subjects with metabolic syndrome Relação entre as adipocinas, inflamação e reatividade vascular em controles magros e pacientes obesos com síndrome metabólica

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    Luciana Bahia

    2006-10-01

    Full Text Available PURPOSE: Metabolic syndrome is an important risk factor for cardiovascular disease. Adipokines interfere with insulin action and endothelial cell function. We investigated the relationship among adipokines, metabolic factors, inflammatory markers, and vascular reactivity in obese subjects with metabolic syndrome and lean controls. METHODS: Cross-sectional study of 19 obese subjects with metabolic syndrome and 8 lean volunteers evaluated as controls. Vascular reactivity was assessed by venous occlusion pletysmography measuring braquial forearm blood flow (FBF and vascular resistance (VR responses to intra-arterial infusions of endothelium-dependent (acetylcholine-Ach and independent (sodium nitroprusside-SNP vasodilators. Blood samples were obtained to evaluate C reactive protein (CRP, plasminogen activator inhibitor 1 (PAI-1, fibrinogen, adiponectin, resistin, and lipid profile. Patients were classified with regard to insulin resistance through the HOMA-IR index. RESULTS: PAI-1, CRP and fibrinogen were higher and adiponectin was lower in metabolic syndrome subjects compared to controls. Metabolic syndrome subjects had impaired vascular reactivity. Adiponectin and PAI-1 were associated with insulin, HOMA-IR, triglycerides, and HDLc; and resistin with CRP. Adiponectin was associated with VR after Ach in the pooled group and resistin with D FBF after Ach in the metabolic syndrome group. CONCLUSION: Metabolic syndrome subjects exhibited low levels of adiponectin and high levels of CRP, fibrinogen, and PAI-1. Adiponectin and PAI-1 correlated with insulin resistance markers. Adiponectin and resistin correlated with vascular reactivity parameters. An adipocyte-endothelium interaction might be an important mechanism of inflammation and vascular dysfunction.A Síndrome Metabólica é um importante fator de risco para doenças cardiovasculares. As adipocinas interferem com a ação da insulina e com a função endotelial. OBJETIVO: Investigar a rela

  4. Systemic Inflammation and Lung Function Impairment in Morbidly Obese Subjects with the Metabolic Syndrome

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    Astrid van Huisstede

    2013-01-01

    Full Text Available Background. Obesity and asthma are associated. There is a relationship between lung function impairment and the metabolic syndrome. Whether this relationship also exists in the morbidly obese patients is still unknown. Hypothesis. Low-grade systemic inflammation associated with the metabolic syndrome causes inflammation in the lungs and, hence, lung function impairment. Methods. This is cross-sectional study of morbidly obese patients undergoing preoperative screening for bariatric surgery. Metabolic syndrome was assessed according to the revised NCEP-ATP III criteria. Results. A total of 452 patients were included. Patients with the metabolic syndrome (n=293 had significantly higher blood monocyte (mean 5.3 versus 4.9, P=0.044 and eosinophil percentages (median 1.0 versus 0.8, P=0.002, while the total leukocyte count did not differ between the groups. The FEV1/FVC ratio was significantly lower in patients with the metabolic syndrome (76.7% versus 78.2%, P=0.032. Blood eosinophils were associated with FEV1/FVC ratio (adj. B −0.113, P=0.018. Conclusion. Although the difference in FEV1/FVC ratio between the groups is relatively small, in this cross-sectional study, and its clinical relevance may be limited, these data indicate that the presence of the metabolic syndrome may influence lung function impairment, through the induction of relative eosinophilia.

  5. The relationship between depression and executive function and the impact of vascular disease burden in younger and older adults

    NARCIS (Netherlands)

    Lugtenburg, Astrid; Voshaar, Richard C. Oude; Van Zelst, Willeke; Schoevers, Robert A.; Enriquez-Geppert, Stefanie; Zuidersma, Marij

    2017-01-01

    Background: depression is associated with worse executive function, but underlying mechanisms might differ by age. Aims: to investigate whether vascular disease burden affects the association between depression and executive dysfunction differentially by age. Method: among 83,613 participants of

  6. Bovine colostrum improves intestinal function following formula-induced gut inflammation in preterm pigs

    DEFF Research Database (Denmark)

    Støy, Ann Cathrine Findal; Heegaard, Peter M. H.; Thymann, Thomas

    2014-01-01

    Background & aims Only few hours of formula feeding may induce proinflammatory responses and predispose to necrotizing enterocolitis (NEC) in preterm pigs. We hypothesized that bovine colostrum, rich in bioactive factors, would improve intestinal function in preterm pigs following an initial...... exposure to formula feeding after some days of total parenteral nutrition (TPN). Methods After receiving TPN for 2 days, preterm pigs were fed formula (FORM, n = 14), bovine colostrum (COLOS, n = 6), or formula (6 h) followed by bovine colostrum (FCOLOS, n = 14). Intestinal lesions, function, and structure...... and FCOLOS pigs, relative to FORM pigs. Intestinal gene expression of serum amyloid A, IL-1β, -6 and -8, and bacterial abundance, correlated positively with NEC severity of the distal small intestine. Conclusions Bovine colostrum restores intestinal function after initial formula-induced inflammation...

  7. Propranolol treatment lowers blood pressure, reduces vascular inflammatory markers and improves endothelial function in obese mice.

    Science.gov (United States)

    da Silva Franco, Nathalia; Lubaczeuski, Camila; Guizoni, Daniele M; Victorio, Jamaira A; Santos-Silva, Junia C; Brum, Patricia C; Carneiro, Everardo M; Davel, Ana P

    2017-08-01

    Obesity-associated hypertension is accompanied by a number of cardiovascular risk factors including vascular insulin resistance (IR) and higher sympathetic nervous activity. Therefore, autonomic blockade was demonstrated to reverse hypertension, endothelial dysfunction and IR in obese individuals. We hypothesized that β-AR blockade with propranolol would restore endothelial function and vascular insulin signaling in obesity, associated with an anti-inflammatory effect. Body weight, systolic blood pressure (SBP), plasma biochemical parameters and aortic endothelial function were analyzed in mice fed standard diet (control group) or a high fat diet (HFD) that were treated with vehicle (water) or propranolol (10mg/kg/day) for 8weeks. Propranolol treatment did not modify obesogenic effect of HFD feeding. However, propranolol was effective in preventing the rise in SBP, the hyperinsulinemia and the impaired endothelium-dependent relaxation to acetylcholine and to insulin in obese mice. Protective effect of propranolol administration in endothelial function was associated with increased nitric oxide (NO) production and phosphorylation of Akt (Ser473) and eNOS (Ser1177), but with reduced phospho-IRS-1(Ser307) and phospho-ERK1/2 (Thr202/Tyr204). In addition, β-blocker propranolol prevented the NF-kB nuclear translocation and the increase in phospho-IκB-α (Ser32) and in interleukin(IL)-6 expression in aorta of obese mice, without significant changes in either aortic reactive oxygen species production or in circulating IL-6 and TNF-α levels. In β2-AR knockout mice, despite increasing body weight and visceral fat, HFD did not increase SBP and showed a partial improvement of endothelial function, revealing a role of β2-AR in cardiovascular effects of obesity. In conclusion, our results suggest that β-AR blockade with propranolol is effective to prevent the endothelial dysfunction, vascular IR and pro-inflammatory state displayed in HFD-induced obesity, independent of

  8. Effects of resistance exercise combined with moderate vascular occlusion on muscular function in humans.

    Science.gov (United States)

    Takarada, Y; Takazawa, H; Sato, Y; Takebayashi, S; Tanaka, Y; Ishii, N

    2000-06-01

    Acute and long-term effects of resistance exercise combined with vascular occlusion on muscular function were investigated. Changes in integrated electromyogram with respect to time (iEMG), vascular resistive index, and plasma lactate concentration were measured in five men either during or after elbow flexion exercises with the proximal end of the arm occluded at 0-100 mmHg. The mean iEMG, postexercise hyperemia, and plasma lactate concentration were all elevated with the increase in occlusion pressure at a low-intensity exercise, whereas they were unchanged with the increase in occlusion pressure at high-intensity exercise. To investigate the long-term effects of low-intensity exercise with occlusion, older women (n = 24) were subjected to a 16-wk exercise training for elbow flexor muscles, in which low-intensity [ approximately 50-30% one repetition maximum (1 RM)] exercise with occlusion at approximately 110 mmHg (LIO), low-intensity exercise without occlusion (LI), and high- to medium-intensity ( approximately 80-50% 1 RM) exercise without occlusion (HI) were performed. Percent increases in both cross-sectional area and isokinetic strength of elbow flexor muscles after LIO were larger than those after LI (P < 0.05) and similar to those after HI. The results suggest that resistance exercise at an intensity even lower than 50% 1 RM is effective in inducing muscular hypertrophy and concomitant increase in strength when combined with vascular occlusion.

  9. Different Impact of Essential Hypertension on Structural and Functional Age-Related Vascular Changes.

    Science.gov (United States)

    Bruno, Rosa Maria; Duranti, Emiliano; Ippolito, Chiara; Segnani, Cristina; Bernardini, Nunzia; Di Candio, Giulio; Chiarugi, Massimo; Taddei, Stefano; Virdis, Agostino

    2017-01-01

    We evaluated whether vascular remodeling is present in physiological aging and whether hypertension accelerates the aging process for vascular function and structure. Small arteries from 42 essential hypertensive patients (HT) and 41 normotensive individuals (NT) were dissected after subcutaneous biopsy. Endothelium-dependent vasodilation (pressurized myograph) was assessed by acetylcholine, repeated under the nitric oxide synthase inhibitor N-nitro-l-arginine methylester or the antioxidant tempol. Structure was evaluated by media-lumen ratio (M/L). Intravascular oxidative generation and collagen deposition were assessed. Inhibition by N-nitro-l-arginine methylester on ACh was inversely related to age in both groups (Phypertension interaction occurred (P=0.0009). In NT, intravascular superoxide emerged in the oldest subgroup, whereas it appeared earlier among HT. Among NT, aged group displayed an increment of collagen fibers versus young group. In HT, collagen deposition was already evident in youngest, with a further enhancement in the aged group. In small arteries, ageing shows a eutrophic vascular remodeling and a reduced nitric oxide availability. Oxidative stress and fibrosis emerge in advanced age. In HT, nitric oxide availability is early reduced, but the progression rate with age is similar. Structural alterations include wide collagen deposition and intravascular reactive oxygen species, and the progression rate with age is steeper. © 2016 American Heart Association, Inc.

  10. Incorporation of bone marrow cells in pancreatic pseudoislets improves posttransplant vascularization and endocrine function.

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    Christine Wittig

    Full Text Available Failure of revascularization is known to be the major reason for the poor outcome of pancreatic islet transplantation. In this study, we analyzed whether pseudoislets composed of islet cells and bone marrow cells can improve vascularization and function of islet transplants. Pancreatic islets isolated from Syrian golden hamsters were dispersed into single cells for the generation of pseudoislets containing 4×10(3 cells. To create bone marrow cell-enriched pseudoislets 2×10(3 islet cells were co-cultured with 2×10(3 bone marrow cells. Pseudoislets and bone marrow cell-enriched pseudoislets were transplanted syngeneically into skinfold chambers to study graft vascularization by intravital fluorescence microscopy. Native islet transplants served as controls. Bone marrow cell-enriched pseudoislets showed a significantly improved vascularization compared to native islets and pseudoislets. Moreover, bone marrow cell-enriched pseudoislets but not pseudoislets normalized blood glucose levels after transplantation of 1000 islet equivalents under the kidney capsule of streptozotocin-induced diabetic animals, although the bone marrow cell-enriched pseudoislets contained only 50% of islet cells compared to pseudoislets and native islets. Fluorescence microscopy of bone marrow cell-enriched pseudoislets composed of bone marrow cells from GFP-expressing mice showed a distinct fraction of cells expressing both GFP and insulin, indicating a differentiation of bone marrow-derived cells to an insulin-producing cell-type. Thus, enrichment of pseudoislets by bone marrow cells enhances vascularization after transplantation and increases the amount of insulin-producing tissue. Accordingly, bone marrow cell-enriched pseudoislets may represent a novel approach to increase the success rate of islet transplantation.

  11. Epidermal growth factor receptor inhibition by erlotinib prevents vascular smooth muscle cell and monocyte-macrophage function in vitro.

    Science.gov (United States)

    Savikko, Johanna; Rintala, Jukka M; Rintala, Sini; Koskinen, Petri

    2015-06-01

    Vascular smooth muscle cells (VSMCs) and monocyte-macrophages play a central role during the development of chronic allograft injury, which still remains an important challenge in organ transplantation. Inflammation, fibrosis and accelerated arteriosclerosis are typical features for chronic allograft injury. Growth factors participate in cell proliferation, differentiation and migration in this pathological process. Here we studied the role of epidermal growth factor receptor (EGFR) in VSMC and monocyte-macrophage function in vitro. EGFR inhibition by erlotinib, a selective EGF tyrosine kinase inhibitor, was studied in VSMC proliferation and migration as well as monocyte-macrophage proliferation and differentiation. Rat coronary artery SMCs were used for VSMC studies. As a model for monocyte-macrophage proliferation and differentiation human monocytic cell line U937 was used. Phorbol ester TPA was used to induce these cells to differentiate into macrophages. Platelet-derived growth factor (PDGF)-B, a known VSMC inducer, caused 2.1-fold stimulation in VSMC proliferation compared to non-stimulated VSMC. Erlotinib prevented this VSMC proliferation in a dose-dependent manner, p < 0.001 in all groups compared to controls. PDGF-B stimulation increased VSMC migration to 2.5-fold when compared with non-stimulated cells. Erlotinib decreased VSMC migration dose-dependently and this effect was significant with all doses, p < 0.05. Erlotinib inhibited dose-dependently the proliferation of U937 monocytic cells, p < 0.001. Erlotinib prevented also TPA-induced macrophage differentiation in a dose-dependent way, p < 0.05. Erlotinib significantly prevents VSMC proliferation and migration in vitro. Erlotinib inhibited also significantly both monocyte proliferation and differentiation. Our data suggest that EGFR inhibition in VSMC and monocyte function has beneficial effects on chronic allograft injury. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Vascular risk factor burden, atherosclerosis, and functional dependence in old age: a population-based study.

    Science.gov (United States)

    Welmer, Anna-Karin; Liang, Yajun; Angleman, Sara; Santoni, Giola; Yan, Zhongrui; Cai, Chuanzhu; Qiu, Chengxuan

    2014-08-01

    Vascular risk factors such as hypertension and obesity have been associated with physical limitations among older adults. The purpose of this study is to examine whether individual and aggregated vascular risk factors (VRFs) are associated with functional dependence and to what extent carotid atherosclerosis (CAS) or peripheral artery disease (PAD) may mediate the possible associations of aggregated VRFs with functional dependence. This cross-sectional study included 1,451 community-living participants aged ≥60 years in the Confucius Hometown Aging Project of China. Data on demographic features, hypertension, high total cholesterol, obesity, smoking, physical inactivity, diabetes, CAS, PAD, and cardiovascular diseases (CVDs) were collected through an interview, a clinical examination, and laboratory tests. Functional dependence was defined as being dependent in at least one activity in the personal or instrumental activities of daily living. Data were analyzed using multiple logistic models controlling for potential confounders. We used the mediation model to explore the potential mediating effect of CAS and PAD on the associations of aggregated VRFs with functional dependence. Of the 1,451 participants, 222 (15.3%) had functional dependence. The likelihood of functional dependence increased linearly with increasing number of VRFs (hypertension, high total cholesterol, abdominal obesity, and physical inactivity) (p for trend <0.002). Mediation analysis showed that controlling for demographics and CVDs up to 11% of the total association of functional dependence with clustering VRFs was mediated by CAS and PAD. Aggregation of multiple VRFs is associated with an increased likelihood of functional dependence among Chinese older adults; the association is partially mediated by carotid and peripheral artery atherosclerosis independently of CVDs.

  13. KLF2 in Regulation of NF-κB-Mediated Immune Cell Function and Inflammation

    Directory of Open Access Journals (Sweden)

    Prerana Jha

    2017-11-01

    Full Text Available KLF2 (Kruppel-like factor 2 is a member of the zinc finger transcription factor family, which critically regulates embryonic lung development, function of endothelial cells and maintenance of quiescence in T-cells and monocytes. It is expressed in naïve T-cells and monocytes, however its level of expression decreases during activation and differentiation. KLF2 also plays critical regulatory role in various inflammatory diseases and their pathogenesis. Nuclear factor-kappaB (NF-κB is an important inducer of inflammation and the inflammation is mediated through the transcription of several proinflammatory cytokines, chemokines and adhesion molecules. So, both transcriptional factors KLF2 and NF-κB are being associated with the similar cellular functions and their maintenance. It was shown that KLF2 regulates most of the NF-κB-mediated activities. In this review, we focused on emphasizing the involvement of KLF2 in health and disease states and how they interact with transcriptional master regulator NF-κB.

  14. Postinfection Irritable Bowel Syndrome: The Links Between Gastroenteritis, Inflammation, the Microbiome, and Functional Disease.

    Science.gov (United States)

    Downs, Ian A; Aroniadis, Olga C; Kelly, Libusha; Brandt, Lawrence J

    Postinfection irritable bowel syndrome (PI-IBS) is a diarrheal disease that develops after infectious gastroenteritis (IGE). Profound alterations in the microbiota accompany IGE yet only 10% of IGE patients progress to PI-IBS. This review explores research linking IGE severity, psychological comorbidity, PI-IBS, and the microbiome in various patient populations. Selective pressures caused by inflammation and increased gastrointestinal motility during gastroenteritis can alter intestinal bacterial phyla including Bacteroidetes, Firmicutes, and Proteobacteria. More specifically, classes such as Bacteroides and Clostridia are differentially abundant in many PI-IBS patients. Altered microbiota may perpetuate a cycle of enteric and systemic inflammation, potently activating neural afferent signaling in the enteric nervous system and causing pain and diarrhea in PI-IBS patients. Altered production of microbial metabolites, for example short chain fatty acids, may have enteric and systemic effects on the host. Longitudinal sampling to characterize changes in the microbiota's genetic, metabolic, and transcriptional activities over time from IGE to PI-IBS may enable improved diagnosis and classification of PI-IBS cases into subtypes, allowing for targeted antibiotic, probiotic, and prebiotic treatments. PI-IBS is a heterogenous and largely organic disease marked by specific alterations in functions of the microbiota and is an important model for studying microbial influences on intestinal, neurological, and psychological host functions.

  15. Glycemic control, inflammation, and cognitive function in older patients with type 2 diabetes.

    Science.gov (United States)

    Akrivos, Jimmy; Ravona-Springer, Ramit; Schmeidler, James; LeRoith, Derek; Heymann, Anthony; Preiss, Rachel; Hoffman, Hadas; Koifman, Keren; Silverman, Jeremy M; Schnaider Beeri, Michal

    2015-10-01

    Glycated hemoglobin (HbA1c) and C-reactive protein (CRP) have been associated with cognitive impairment independently. However, it is unclear if their combination exacerbates poor cognitive function. We assessed whether long-term glycemic level and glycemic variability modulate the association of systemic inflammation with cognitive function, in a sample of cognitively normal older people with type 2 diabetes. A retrospective cohort study of 777 randomly selected participants from ~11,000 patients in the Maccabi Healthcare Services Diabetes Registry, as part of the Israel Diabetes and Cognitive Decline study. Subjects averaged 18 (±9.4) HbA1c measures in the Maccabi Healthcare Services Registry, which were used to calculate long-term glycemic level (HbA1c-mean) and glycemic variability (HbA1c-standard deviation (SD)). Linear regression models assessed the interactions of CRP, a marker of systemic inflammation, with HbA1c-mean and HbA1c-SD on subjects' performance in tests of Memory, Executive Functions, Attention, and Semantic Categorization. Quadratic interactions of CRP with HbA1c-SD approached significance for executive functions and overall cognition. However, after Bonferroni adjustment, none of the interactions of CRP with HbA1c were statistically significant. In partial correlations according to HbA1c-SD tertiles, CRP was weakly correlated in the middle tertile with decreased performance in the domains of semantic categorization (r = -0.166, p = 0.011), executive functions (r = -0.136, p = 0.038), and overall cognition (r = -0.157, p = 0.016). Glycated hemoglobin does not substantially modulate the association of CRP with cognition in a sample of cognitively normal, community dwelling older people with relatively well-managed type 2 diabetes. Copyright © 2015 John Wiley & Sons, Ltd.

  16. Relationships between measures of fitness, physical activity, body composition and vascular function in children.

    Science.gov (United States)

    Hopkins, N D; Stratton, G; Tinken, T M; McWhannell, N; Ridgers, N D; Graves, L E F; George, K; Cable, N T; Green, D J

    2009-05-01

    The prevalence of obesity and physical inactivity in Western countries has increased rapidly. Both are modifiable risk factors for cardiovascular disease. Atherosclerosis begins in childhood and endothelial dysfunction is its earliest detectable manifestation. We assessed flow-mediated dilation (FMD) in 129 children (75 female; 10.3+0.3 yrs; 54 male; 10.4; 0.3 yrs). FMD was normalised for differences in the eliciting shear rate stimulus between subjects (SR(AUC)). Fitness was assessed as peak oxygen uptake during an incremental treadmill exercise test (V O(2)peak). Body composition was measured using a dual-energy X-ray absorptiometry (DEXA) scan. Physical activity (PA) was assessed using Actigraph accelerometers. The cohort was split into tertiles according to FMD% and also FMD% corrected for SR(AUC) to gain insight into the determinants of vascular function. Across the cohort, significant correlations were observed between FMD%/SR(AUC) and DEXA percentage fat (r=-0.23, p=0.009) and percentage lean mass (r=0.21, p=0.008), and also with PA performed at moderate-to-high intensity (r=0.363, p=0.001). For children in the lowest FMD%/SR(AUC) tertile, a stronger relationship with all PA measures was observed, particularly with high intensity PA (r=0.572, P=0.003). Regression analysis revealed that high intensity PA was the only predictor of impaired FMD%/SR(AUC). These data suggest that traditional risk factors for CHD in adult populations impact upon vascular function in young people. Furthermore, it appears that individuals with impaired FMD may benefit from performing high intensity PA, whereas no relationships exist between FMD and lower intensities of PA or between PA and FMD in those subjects who possess preserved vascular function a priori.

  17. Substance P antagonist CP-96345 blocks lung vascular leakage and inflammation more effectively than its stereoisomer CP-96344 in a mouse model of smoke inhalation and burn injury.

    Science.gov (United States)

    Jacob, Sam; Deyo, Donald J; Cox, Robert A; Jacob, Reuben K; Herndon, David N; Traber, Daniel L; Hawkins, Hal K

    2010-05-01

    The recently developed murine model of smoke inhalation and burn (SB) injury was used to study the effect of the substance-P antagonist CP96345. C57BL/6 mice were pre-treated with an i.v. dose of a specific NK-1 receptor antagonist, CP9635, or its inactive enantiomer, CP96344, (10 mg/Kg) 1 h prior to SB injury per protocol (n = 5). Mice were anesthetized and exposed to cooled cotton smoke, 2X 30 s, followed by a 40% total body surface area flame burn per protocol. At 48 h after SB injury Evans Blue (EB) dye and myeloperoxidase (MPO) were measured in lung after vascular perfusion. Lungs were also analyzed for hemoglobin (Hb) and wet/dry weight ratio. In the current study, CP96345 pre-treatment caused a significant decrease in wet/dry weight ratio (23%, p = 0.048), EB (31%, p = 0.047), Hb (46%, p = 0.002), and MPO (54%, p = 0.037) levels following SB injury compared to animals with SB injury alone. CP-96344 pre-treatment caused an insignificant decrease in wet/dry weight ratio (14%, p = 0.18), EB (16%, p = 0.134), Hb (9%, p = 0.39), and an insignificant increase in MPO (4%, p = 0.79) as compared to mice that received SB injury alone. As expected, levels of EB, Hb, MPO, and wet/dry weight ratios were all significantly (p CP-96345 attenuates the lung injury and inflammation induced by SB injury in mice.

  18. Bromodomain and extra-terminal protein mimic JQ1 decreases inflammation in human vascular endothelial cells: Implications for pulmonary arterial hypertension.

    Science.gov (United States)

    Mumby, Sharon; Gambaryan, Natalia; Meng, Chao; Perros, Frederic; Humbert, Marc; Wort, S John; Adcock, Ian M

    2017-01-01

    Nuclear factor kappa B (NF-kB)-mediated inflammatory gene expression and vascular endothelial cell proliferation/remodelling are implicated in the pathophysiology of the fatal disease, pulmonary arterial hypertension (PAH). Bromodomain and extra-terminal (BET) proteins are essential for the expression of a subset of NF-kB-induced inflammatory genes. BET mimics including JQ1+ prevent binding of BETs to acetylated histones and down-regulate the expression of selected genes. The effects of JQ1+ on the proliferation of primary human pulmonary microvascular endothelial cells (HPMECs) from healthy subjects were measured by bromodeoxyuridine (BrdU) incorporation. Cell cycle progression was assessed by flow cytometry; mRNA and protein levels of cyclin-dependent kinases (CDKs), inhibitors and cytokines were determined by reverse transcription-quantitative PCR (RT-qPCR), Western blotting or ELISA. Histone acetyltransferase (HAT) and deacetylase (HDAC) activities were determined in nuclear extracts from whole lung of PAH and control patients. JQ1+ significantly inhibited IL6 and IL8 (IL6 and CXCL8) mRNA and protein in HPMECs compared with its inactive enantiomer JQ1-. JQ1+ decreased NF-kB p65 recruitment to native IL6 and IL8 promoters. JQ1+ showed a concentration-dependent decrease in HPMEC proliferation compared with JQ1--treated cells. JQ1+ induced G1 cell cycle arrest by increasing the expression of the CDK inhibitors (CDKN) 1A (p21 cip ) and CDKN2D (p19 INK4D ) and decreasing that of CDK2, CDK4 and CDK6. JQ1+ also inhibited serum-stimulated migration of HPMECs. Finally, HAT activity was significantly increased in the lung of PAH patients. Inhibition of BETs in primary HPMECs decreases inflammation and remodelling. BET proteins could be a target for future therapies for PAH. © 2016 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.

  19. Early treatment with losartan effectively ameliorates hypertension and improves vascular remodeling and function in a prehypertensive rat model.

    Science.gov (United States)

    He, De-Hua; Lin, Jin-Xiu; Zhang, Liang-Min; Xu, Chang-Sheng; Xie, Qiang

    2017-03-15

    Pharmacological treatment of prehypertension may ameliorate hypertension and improve vascular structure and function. This study investigated 1) whether early treatment with either losartan or amlodipine at the onset of prehypertension can prevent hypertension and 2) whether losartan and amlodipine equally improve vascular remodeling and function in a rat model of hypertension. Stroke-prone spontaneously hypertensive (SHRSP) rats were administered losartan, amlodipine or saline for 6 or 16weeks at the onset of prehypertension. Wistar-Kyoto rats were used as a control. All groups were observed for 40weeks. Systolic blood pressure was measured using the tail-cuff method. Vascular structure and function were determined by microscopy and vascular ring contractility assays, respectively. Angiotensin II (Ang II) and aldosterone (Aldo) were measured by radioimmunoassays. Angiotensin II type 1 receptor (AT1R) and angiotensin II type 2 receptor (AT2R) expression was measured by western blot. Losartan effectively reduced progression from prehypertension to hypertension as well as vascular remodeling and improved vascular contractility in SHRSP rats. Long-term losartan (16weeks) had greater benefits than short-term (6weeks) treatment. Losartan increased Ang II and decreased Aldo levels in the serum and vessel walls of resistance vessels in a time-dependent manner. Losartan significantly decreased AT1R and increased AT2R vascular expression. Amlodipine had no effect on vascular AT1R and AT2R expression. Losartan administered at the onset of prehypertension is more effective than amlodipine in ameliorating hypertension and improving vascular remodeling and function, which is likely mediated by the renin-angiotensin-aldosterone system. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Effects of N-acetyl-cysteine on endothelial function and inflammation in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    David J. Cohen

    2009-04-01

    Full Text Available Endothelial dysfunction has been associated with premature vascular disease. There is increasing data that N-acetyl-cysteine (NAC may prevent or improve endothelial dysfunction. The aim of this study was to assess the effects of NAC on endothelial function in patients with type 2 diabetes mellitus, a population at high risk for endothelial dysfunction. Twenty-four patients with diabetes mellitus were assigned randomly to initial therapy with either 900 mg NAC or placebo twice daily in a double-blind, cross-over study design. Flow-mediated vasodilation (FMD of the brachial artery was assessed at baseline, after four weeks of therapy, after a four-week wash-out period, and after another four weeks on the opposite treatment. Plasma and red blood cell glutathione levels and high-sensitivity C-reactive protein (CRP were measured at all four visits. At baseline, FMD was moderately impaired (3.7±2.9%. There was no significant change in FMD after four weeks of NAC therapy as compared to placebo (0.1±3.6% vs. 1.2±4.2%. Similarly, there was no significant change in glutathione levels. However, median CRP decreased from 2.35 to 2.14 mg/L during NAC therapy (p=0.04, while it increased from 2.24 to 2.65 mg/L with placebo. No side effects were noted during the treatment period. In this double-blind, randomized cross-over study, four weeks of oral NAC therapy failed to improve endothelial dysfunction in patients with diabetes mellitus. However, NAC therapy decreased CRP levels, suggesting that this compound may have some efficacy in reducing systemic inflammation.

  1. Vascular function long term after Kawasaki disease: another piece of the puzzle?

    Science.gov (United States)

    Pinto, Fátima F; Gomes, Inês; Loureiro, Petra; Laranjo, Sérgio; Timóteo, Ana T; Carmo, Miguel M

    2017-04-01

    Kawasaki disease is an acute systemic vasculitis. Cardiac complications are frequent and include endothelial dysfunction in patients with coronary anomalies. Thus far, endothelial dysfunction in patients with no coronary lesions is poorly understood. Our aim was to access the vascular function in adolescents and young adults long term after Kawasaki disease, but without coronary aneurysms or any other cardiac risk factors. We carried out a single-centre prospective study in a Portuguese population. We evaluated two groups of subjects: (1) Kawasaki disease patients over 11 years of age, diagnosed >5 years ago, with no coronary lesions or any other risk factors for cardiovascular disease; (2) control group of individuals without cardiovascular risk factors. Patients and controls were clinically assessed. Endo-PAT and carotid intima-media thickness assessment were performed to determine vascular function. In total, 43 Kawasaki disease patients were assessed and compared with 43 controls. Kawasaki disease patients presented a decreased reactive hyperaemia index compared with controls (1.59±0.45 versus 1.98±0.41; pKawasaki disease group. There were no statistically significant changes with regard to laboratory data. Children with Kawasaki disease may have long-term sequelae, even when there is no discernible coronary artery involvement in the acute stage of the disease. Further research is needed to assess whether known strategies to improve endothelial function would bring potential benefits to Kawasaki disease patients.

  2. The effects of ionizing radiation on the function and vascular structure of the rat submandibular gland

    Energy Technology Data Exchange (ETDEWEB)

    Kawamata, Fumio (Nippon Dental Univ., Tokyo (Japan))

    1991-06-01

    In radiotherapy for the jaw and face, the irradiation field frequently affects the salivary gland, in an aduerse way. In the present study, I assessed the functional influence of radiation on the submandibular gland by RI, with inspection of both the vascular distribution of the submandibular gland by India ink and resin molding methods, and of the histological changes by HE and PAS staining. Each experimental group consisted of 9 male Wistar strain rats aged 8 weeks. Single irradiation was performed at 10 Gy and 50 Gy doses by {sup 60}Co-{gamma} ray. The changes at 6 hours, 3, 7, 14, and 28 days after irradiation were determined and compared with those in the control group. Function tests for uptake and clearance were performed using {sup 99m}TcO{sub 4}{sup -}. Results showed the uptake and clearance value in the irradiation group was higher than that in the control group. With respect to the effect of irradiation on blood vessels, vasodilation, flexion, and destruction of the blood wall were observed. In addition, various histological changes appeared. In each examination, the irradiation effects in the 50 Gy group were greater than those in the 10 Gy group. In conclusion, the decline in submandibular function after 10 Gy and 50 Gy irradiation is related to histological changes in the vascular system and glandular tissues. (author) 63 refs.

  3. Pycnogenol Ameliorates Asthmatic Airway Inflammation and Inhibits the Function of Goblet Cells.

    Science.gov (United States)

    Liu, Zhaoe; Han, Bo; Chen, Xing; Wu, Qiaoling; Wang, Lijun; Li, Gang

    2016-11-01

    Pycnogenol® (PYC) is utilized in the treatment of various diseases ranging from chronic inflammation to circulatory diseases, but its efficacy and functional mechanism in pediatric asthma continue to remain obscure. Therefore, the purpose of this study was to investigate the effectiveness and molecular mechanism of PYC on regulation of asthmatic airway inflammation. We found that PYC with tail intravenous injection of 50 mg/kg or intragastric administration of 100 mg/kg all reduced ovalbumin (OVA)-induced airway injury. Pharmacokinetics of PYC was evaluated by high-performance liquid chromatography assay, indicating that PYC was quickly absorbed into the blood after intragastric administration, and PYC metabolism was later improved gradually with increase of time after PYC administration. PYC has a higher bioavailability of 71.96%, and it was more easily absorbed by the body. PYC inhibited the number of total inflammatory cells and levels of interleukin (IL)-4, IL-5, IL-9, and IL-13 in bronchoalveolar lavage fluid of OVA-induced mice. PYC inhibited IL-13 secretion from the Th2 cells, thereby causing a reduction in expression of the signaling molecules in JAK/STAT6 pathway in airway epithelial cells. STAT6 silence suppressed IL-13-increased acetylcholine level. STAT6 overexpression promoted expression of goblet cell metaplasia-associated molecules (FOXA3, SPDEF, and Muc5ac). PYC suppressed OVA-induced expression of FOXA3, SPDEF, and Muc5ac in lung. Our findings indicate that PYC has a higher bioavailability and it prevents emergence of OVA-induced airway injury and airway inflammation in mice by inhibiting IL-13/JAK/STAT6 pathway and blocking release of acetylcholine to reduce goblet cell metaplasia.

  4. Functional reconstruction of subtotal thumb metacarpal defect with a vascularized medial femoral condyle flap: case report.

    Science.gov (United States)

    Wong, Victor W; Higgins, James P; Katz, Ryan D

    2014-10-01

    Devastating hand injuries require customized reconstructive strategies to maximize functional outcomes. We report a case of thumb metacarpal reconstruction using a vascularized medial femoral condyle osteocutaneous flap in the setting of nearly complete metacarpal loss. In addition to achieving the traditional goals of reconstructing thumb length and providing stability, the medial femoral condyle flap allowed motion at the carpometacarpal joint. The patient's hand function was further optimized by a component transfer of a proximally injured but distally preserved index finger to the amputated middle finger position. The patient regained satisfactory grip and thumb function with minimal donor site morbidity. This case highlights the role of both creative and established approaches to reconstruct composite tissues following devastating hand injury. Copyright © 2014 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  5. Neuroimaging Biomarkers of Caloric Restriction on Brain Metabolic and Vascular Functions.

    Science.gov (United States)

    Lin, Ai-Ling; Parikh, Ishita; Hoffman, Jared D; Ma, David

    2017-03-01

    Non-invasive neuroimaging methods have been developed as powerful tools for identifying in vivo brain functions for studies in humans and animals. Here we review the imaging biomarkers that are being used to determine the changes within brain metabolic and vascular functions induced by caloric restriction (CR), and their potential usefulness for future studies with dietary interventions in humans. CR causes an early shift in brain metabolism of glucose to ketone bodies, and enhances ATP production, neuronal activity and cerebral blood flow (CBF). With age, CR preserves mitochondrial activity, neurotransmission, CBF, and spatial memory. CR also reduces anxiety in aging mice. Neuroimaging studies in humans show that CR restores abnormal brain activity in the amygdala of women with obesity and enhances brain connectivity in old adults. Neuroimaging methods have excellent translational values and can be widely applied in future studies to identify dietary effects on brain functions in humans.

  6. Systemic inflammation in young adults is associated with abnormal lung function in middle age.

    Directory of Open Access Journals (Sweden)

    Ravi Kalhan

    2010-07-01

    Full Text Available Systemic inflammation is associated with reduced lung function in both healthy individuals and those with chronic obstructive pulmonary disease (COPD. Whether systemic inflammation in healthy young adults is associated with future impairment in lung health is uncertain.We evaluated the association between plasma fibrinogen and C-reactive protein (CRP in young adults and lung function in the Coronary Artery Risk Development in Young Adults cohort study. Higher year 7 fibrinogen was associated with greater loss of forced vital capacity (FVC between years 5 and 20 (439 mL in quartile 4 vs. 398 mL in quartile 1, P<0.001 and forced expiratory volume in 1 second (FEV(1 (487 mL in quartile 4 vs. 446 mL in quartile 1, P<0.001 independent of cigarette smoking, body habitus, baseline lung function and demographic factors. Higher year 7 CRP was also associated with both greater loss of FVC (455 mL in quartile 4 vs. 390 mL in quartile 1, P<0.001 and FEV(1 (491 mL in quartile 4 vs. 442 mL in quartile 1, P = 0.001. Higher year 7 fibrinogen and CRP were associated with abnormal FVC at year 20 (odds ratio (OR per standard deviation 1.51 (95% confidence interval (CI: 1.30-1.75 for fibrinogen and 1.35 (95% CI: 1.14-1.59 for CRP. Higher year 5 fibrinogen was additionally associated with abnormal FEV(1. A positive interaction was observed between pack-years cigarette smoking and year 7 CRP for the COPD endpoint, and among participants with greater than 10 pack-years of cigarette exposure, year 7 CRP was associated with greater odds of COPD at year 20 (OR per standard deviation 1.53 (95% CI: 1.08-2.16.Systemic inflammation in young adults is associated with abnormal lung function in middle age. In particular, elevated CRP may identify vulnerability to COPD among individuals who smoke.ClinicalTrials.gov NCT00005130.

  7. A continuum of executive function deficits in early subcortical vascular cognitive impairment: A systematic review and meta-analysis

    Science.gov (United States)

    Sudo, Felipe Kenji; Amado, Patricia; Alves, Gilberto Sousa; Laks, Jerson; Engelhardt, Eliasz

    2017-01-01

    ABSTRACT. Background. Subcortical Vascular Cognitive Impairment (SVCI) is a clinical continuum of vascular-related cognitive impairment, including Vascular Mild Cognitive Impairment (VaMCI) and Vascular Dementia. Deficits in Executive Function (EF) are hallmarks of the disorder, but the best methods to assess this function have yet to be determined. The insidious and almost predictable course of SVCI and the multidimensional concept of EF suggest that a temporal dissociation of impairments in EF domains exists early in the disorder. Objective: This study aims to review and analyze data from the literature about performance of VaMCI patients on the most used EF tests through a meta-analytic approach. Methods: Medline, Web of Knowledge and PsycINFO were searched, using the terms: “vascular mild cognitive impairment” OR “vascular cognitive impairment no dementia” OR “vascular mild neurocognitive disorder” AND “dysexecutive” OR “executive function”. Meta-analyses were conducted for each of the selected tests, using random-effect models. Results: Systematic review showed major discrepancies among the results of the studies included. Meta-analyses evidenced poorer performance on the Trail-Making Test part B and the Stroop color test by VaMCI patients compared to controls. Conclusion: A continuum of EF impairments has been proposed in SVCI. Early deficits appear to occur in cognitive flexibility and inhibitory control. PMID:29354217

  8. Plasma Neutrophil Gelatinase-Associated Lipocalin Reflects Both Inflammation and Kidney Function in Patients with Myocardial Infarction

    DEFF Research Database (Denmark)

    Lindberg, Søren; Jensen, Jan S; Hoffmann, Søren

    2016-01-01

    BACKGROUND/AIMS: Neutrophil gelatinase-associated lipocalin (NGAL) has emerged as a marker for acute kidney injury and cardiovascular outcome. However, the relative importance of inflammation versus kidney function on plasma NGAL levels is uncertain, making the interpretation of plasma NGAL unclear....... Accordingly, we investigated the relationship between plasma NGAL, inflammation and kidney function in patients with myocardial infarction (MI). METHODS: We prospectively included 584 patients with acute ST-segment elevation MI (STEMI) treated with primary percutaneous coronary intervention (PCI) from 2006.......001). Leukocyte count and C-reactive protein were the main determinants of plasma NGAL in patients with normal eGFR, whereas eGFR was the main determinant at reduced kidney function. CONCLUSIONS: eGFR determines the association of NGAL with either inflammation or kidney function; in patients with normal e...

  9. Escherichia coli heat-labile detoxified enterotoxin modulates dendritic cell function and attenuates allergic airway inflammation.

    Directory of Open Access Journals (Sweden)

    I-Ping Lin

    Full Text Available Various mutant forms of Escherichia coli heat-labile enterotoxin (LT have been used as a mucosal adjuvant for vaccines, as it enhances immune responses to specific antigens including antigen-specific IgA antibodies when administrated intranasally or orally. We hypothesized that a detoxified mutant form of LT, LTS61K, could modulate dendritic cell (DC function and alleviate allergen-induced airway inflammation. Two protocols, preventative and therapeutic, were used to evaluate the effects of LTS61K in a Dermatophagoides pteronyssinus (Der p-sensitized and challenged murine model of asthma. LTS61K or Der p-primed bone marrow-derived dendritic cells (BMDCs were also adoptively transferred into Der p-sensitized and challenged mice. Intranasal inoculations with LTS61K or LTS61K/Der p decreased allergen-induced airway inflammation and alleviated systemic TH2-type immune responses. Bronchoalveolar lavage fluid (BALF and sera from LTS61K/Der p-treated mice also had higher concentrations of Der p-specific immunoglobulin (Ig A than those of other groups. In vitro, BMDCs stimulated with Der p underwent cellular maturation and secreted proinflammatory cytokines interleukin (IL-6 and tumor necrosis factor (TNFα In contrast, Der p-stimulated BMDCs that were pretreated with LTS61K showed decreased IL-6 and TNFα production and were less mature. Intratracheal adoptive transfer of LTS61K- or LTS61K/Der p-primed BMDCs into Der p-sensitized mice reduced inflammatory cell infiltration and TH2-type chemokines in BALF and alleviated airway inflammation in treated mice. LTS61K influenced DC maturation and decreased inflammatory cytokine production. Moreover, LTS61K/Der p induced increased Der p-specific IgA production to decrease allergic TH2 cytokine responses and alleviated airway inflammation in Der p-sensitized mice. These results suggest that the immunomodulatory effects of LTS61K may have clinical applications for allergy and asthma treatment.

  10. Comparison of sevelamer and calcium carbonate on endothelial function and inflammation in patients on peritoneal dialysis.

    Science.gov (United States)

    Chennasamudram, Sudha P; Noor, Tanjila; Vasylyeva, Tetyana L

    2013-06-01

    Hyperphosphataemia is a known independent risk factor for cardiovascular mortality. The objective of the study was to compare the effects of two phosphate binders, sevelamer carbonate and calcium carbonate on endothelial function (EF) and inflammation in patients on peritoneal dialysis (PD) with Type 2 diabetes mellitus (T2DM). Fifteen subjects with hyperphosphataemia discontinued all phosphate binders to undergo a two-week washout and were assigned to sevelamer carbonate or calcium carbonate treatments for eight weeks. After a second two-week washout period, subjects crossed over to either of the alternate treatments for another eight weeks. At the beginning and end of each treatment, biomarkers of EF, pro-inflammatory cytokines, serum albumin, calcium, phosphate and lipids were measured. Sevelamer carbonate significantly improved lipid profile compared with calcium carbonate. Amongst the EF and pro-inflammatory biomarkers, sevelamer carbonate decreased serum endothelin-1, plasminogen activator inhibitor-1, C-reactive protein and interleukin-6. Both phosphate binders were effective in decreasing serum phosphate but sevelamer had a positive effect on EF. Treatment with sevelamer carbonate has beneficial effects compared with calcium carbonate in decreasing inflammation and improving EF in patients with T2DM on PD. © 2013 European Dialysis and Transplant Nurses Association/European Renal Care Association.

  11. Endothelial mechanotransduction proteins and vascular function are altered by dietary sucrose supplementation in healthy young male subjects

    DEFF Research Database (Denmark)

    Gliemann, Lasse; Rytter, Nicolai; Lindskrog, Mads

    2017-01-01

    Endothelial mechanotransduction is important for vascular function but alterations and activation of vascular mechanosensory proteins have not been investigated in humans. In endothelial cell culture, simple sugars effectively impair mechanosensor proteins. To study mechanosensor- and vascular...... by ultrasound doppler. A muscle biopsy was obtained from the thigh muscle before and after acute passive leg movement, to asses the protein amount and phosphorylation status of mechanosensory proteins and NADPH oxidase. The sucrose intervention led to a reduced flow response to passive movement (by 17 ± 2...... %) and to 12 watts of active exercise (by 9 ± 1 %), indicating impaired vascular function. Reduced flow response to passive and active exercise was paralleled by a significant upregulation of Platelet endothelial cell adhesion molecule (PECAM-1), endothelial nitric oxide synthase, NADPH oxidase and the Rho...

  12. Impaired respiratory function and heightened pulmonary inflammation in episodic binge ethanol intoxication and burn injury.

    Science.gov (United States)

    Shults, Jill A; Curtis, Brenda J; Chen, Michael M; O'Halloran, Eileen B; Ramirez, Luis; Kovacs, Elizabeth J

    2015-11-01

    Clinical data indicate that cutaneous burn injuries covering greater than 10% of the total body surface area are associated with significant morbidity and mortality, in which pulmonary complications, including acute respiratory distress syndrome (ARDS), contribute to nearly half of all patient deaths. Approximately 50% of burn patients are intoxicated at the time of hospital admission, which increases days on ventilators by 3-fold, and doubles the length of hospitalization, compared to non-intoxicated burn patients. The most common drinking pattern in the United States is binge drinking, where an individual rapidly consumes alcoholic beverages (4 for women, 5 for men) in 2 h. An estimated 38 million Americans binge drink, often several times per month. Experimental data demonstrate that a single binge-ethanol exposure, prior to scald injury, impairs innate and adaptive immune responses, thereby enhancing infection susceptibility and amplifying pulmonary inflammation, neutrophil infiltration, and edema, and is associated with increased mortality. Since these characteristics are similar to those observed in ARDS burn patients, our study objective was to determine whether ethanol intoxication and burn injury and the subsequent pulmonary congestion affect physiological parameters of lung function, using non-invasive and unrestrained plethysmography in a murine model system. Furthermore, to mirror young adult binge-drinking patterns, and to determine the effect of multiple ethanol exposures on pulmonary inflammation, we utilized an episodic binge-ethanol exposure regimen, where mice were exposed to ethanol for a total of 6 days (3 days ethanol, 4 days rest, 3 days ethanol) prior to burn injury. Our analyses demonstrate mice exposed to episodic binge ethanol and burn injury have higher mortality, increased pulmonary congestion and neutrophil infiltration, elevated neutrophil chemoattractants, and respiratory dysfunction, compared to burn or ethanol intoxication alone

  13. Low-grade systemic inflammation: a partial mediator of the relationship between diabetes and lung function.

    Science.gov (United States)

    Giovannelli, Jonathan; Trouiller, Philippe; Hulo, Sébastien; Chérot-Kornobis, Natalie; Ciuchete, Alina; Edmé, Jean-Louis; Matran, Régis; Amouyel, Philippe; Meirhaeghe, Aline; Dauchet, Luc

    2018-01-01

    An association has been consistently found between diabetes mellitus and decreased lung function. We evaluated to what extent low-grade inflammation (as measured by the level of high-sensitivity C-reactive protein [hs-CRP]) could explain this relationship. A sample of 1878 middle-aged adults from the cross-sectional Enquête Littoral Souffle Air Biologie Environnement survey without self-reported pulmonary and atherosclerosis disease was included. A mediation analysis was performed to assess and quantify the hs-CRP level as a mediator of the relationship between diabetes and lung function. Diabetes was associated with higher hs-CRP level (+22.9%, 95% confidence interval = [5.1, 43.6]). The hs-CRP (>4 vs. ≤1 mg/L) was associated with lower percentage predicted values for the forced expiratory volume in the first second (FEV1) (-4% [-6.1, -1.9]) and forced vital capacity (FVC) (-4.4% [-6.5, -2.3]). Diabetes was associated with FEV1 (-3.5% [-5.8, -1.3]) and FVC (-3.6% [-5.9, -1.3]). The proportion of the effect that is mediated by hs-CRP was 12% [2.4, 37] and 13% [3.7, 39.4] for FEV1 and FVC, respectively. Our results suggest that low-grade systemic inflammation could only explain a small part of the relationship between diabetes and lung function. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Evidence for a role of hot flushes in vascular function in recently postmenopausal women.

    Science.gov (United States)

    Tuomikoski, Pauliina; Ebert, Pia; Groop, Per-Henrik; Haapalahti, Petri; Hautamäki, Hanna; Rönnback, Mats; Ylikorkala, Olavi; Mikkola, Tomi S

    2009-04-01

    Observational studies indicate that postmenopausal hormone therapy (HT) prevents cardiovascular disease, but randomized clinical trials have not confirmed this effect. Hot flushes were more likely to be present in women starting HT in observational studies, whereas these symptoms were mild or absent among women attending randomized clinical trials. We hypothesized that vascular function may differ in women with and without vasomotor hot flushes. One hundred forty-three recently postmenopausal women showing a broad range of variation in hot flushes were studied with radial artery tonometry. Pulse wave analyses were assessed at baseline and after nitroglycerin and salbutamol challenges. Wilcoxon signed rank test was used for paired comparisons after challenges with nitroglycerin and salbutamol. Neither baseline arterial stiffness nor endothelial function differed between women without or with mild, moderate, or severe hot flushes. However, after nitroglycerin challenge, the time to the onset of the reflected wave (dependent on pulse wave velocity) was 9.5% longer (P=.014), and the time to the first systolic peak (dependent on the rapid phase of ventricular ejection) was 13.9% longer (P=.025) in women with severe hot flushes as compared with asymptomatic women. Women with severe vasomotor hot flushes show greater vascular responsiveness to nitroglycerin than women without hot flushes. This may partially explain the conflicting data between observational and randomized HT studies. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00668603 II.

  15. Single-cell profiling reveals heterogeneity and functional patterning of GPCR expression in the vascular system.

    Science.gov (United States)

    Kaur, H; Carvalho, J; Looso, M; Singh, P; Chennupati, R; Preussner, J; Günther, S; Albarrán-Juárez, J; Tischner, D; Classen, S; Offermanns, S; Wettschureck, N

    2017-06-16

    G-protein-coupled receptor (GPCR) expression is extensively studied in bulk cDNA, but heterogeneity and functional patterning of GPCR expression in individual vascular cells is poorly understood. Here, we perform a microfluidic-based single-cell GPCR expression analysis in primary smooth muscle cells (SMC) and endothelial cells (EC). GPCR expression is highly heterogeneous in all cell types, which is confirmed in reporter mice, on the protein level and in human cells. Inflammatory activation in murine models of sepsis or atherosclerosis results in characteristic changes in the GPCR repertoire, and we identify functionally relevant subgroups of cells that are characterized by specific GPCR patterns. We further show that dedifferentiating SMC upregulate GPCRs such as Gpr39, Gprc5b, Gprc5c or Gpr124, and that selective targeting of Gprc5b modulates their differentiation state. Taken together, single-cell profiling identifies receptors expressed on pathologically relevant subpopulations and provides a basis for the development of new therapeutic strategies in vascular diseases.

  16. Polydopamine-mediated immobilization of multiple bioactive molecules for the development of functional vascular graft materials.

    Science.gov (United States)

    Lee, Yu Bin; Shin, Young Min; Lee, Ji-Hye; Jun, Indong; Kang, Jae Kyeong; Park, Jong-Chul; Shin, Heungsoo

    2012-11-01

    In this study, we introduced a simple method for polydopamine-mediated immobilization of dual bioactive factors for the preparation of functionalized vascular graft materials. Polydopamine was deposited on elastic and biodegradable poly(lactic acid-co-ɛ-caprolactone) (PLCL) films, and a cell adhesive RGD-containing peptide and basic fibroblast growth factor were subsequently immobilized by simple dipping. We used an enzyme-linked immunosorbent assay and fluorescamine assay to confirm that we had stably immobilized bioactive molecules on the polydopamine-coated PLCL film in a reaction time-dependent manner. When human umbilical vein endothelial cells (HUVEC) were cultured on the prepared substrates, the number of adherent cells and proliferation of HUVEC for up to 14 days were greatest on the film immobilized with dual factors. On the other hand, the film immobilized with RGD peptide exhibited the highest migration speed compared to the other groups. The expression of cluster of differentiation 31 and von Willebrand factor, which indicates maturation of endothelial cells, was highly stimulated in the dual factor-immobilized group, and passively adsorbed factors showed a negligible effect. The immobilization of bioactive molecules inspired by polydopamine was successful, and adhesion, migration, proliferation and differentiation of HUVEC were synergistically accelerated by the presence of multiple signaling factors. Collectively, our results have demonstrated that a simple coating with polydopamine enables the immobilization of multiple bioactive molecules for preparation of polymeric functionalized vascular graft materials. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Plasma norepinephrine is an independent predictor of vascular endothelial function with aging in healthy women.

    Science.gov (United States)

    Kaplon, Rachelle E; Walker, Ashley E; Seals, Douglas R

    2011-11-01

    We tested the hypothesis that reductions in vascular endothelial function (endothelium-dependent dilation, EDD) with age are related to increases in sympathetic activity. Among 314 healthy men and women, age was inversely related to brachial artery flow-mediated dilation (FMD) (r = -0.30, P women (n = 127, r = -0.37, P women (r = -0.16, P = 0.06). Consistent with this, brachial FMD remained significantly related to PNE when controlling for age (r = -0.24, P women. Indeed, PNE was the strongest independent correlate of brachial FMD in women after controlling for conventional cardiovascular disease risk factors (r = -0.22, P = 0.01). This relation persisted in a subset of women (n = 113) after further accounting for the effects of plasma oxidized low-density lipoprotein (P independent dilation was not related to age in either men or women (P > 0.05). These results provide the first evidence that EDD is inversely related to sympathetic activity, as assessed by PNE, among healthy adults varying in age. In particular, our findings suggest that sympathetic nervous system activity may be a key factor involved in the modulation of vascular endothelial function with aging in women.

  18. A Randomized Trial of Vitamin D Supplementation on Vascular Function in CKD.

    Science.gov (United States)

    Kumar, Vivek; Yadav, Ashok Kumar; Lal, Anupam; Kumar, Vinod; Singhal, Manphool; Billot, Laurent; Gupta, Krishan Lal; Banerjee, Debasish; Jha, Vivekanand

    2017-10-01

    Vitamin D deficiency associates with mortality in patients with CKD, and vitamin D supplementation might mitigate cardiovascular disease risk in CKD. In this randomized, double-blind, placebo-controlled trial, we investigated the effect of cholecalciferol supplementation on vascular function in 120 patients of either sex, aged 18-70 years, with nondiabetic CKD stage 3-4 and vitamin D deficiency (serum 25-hydroxyvitamin D ≤20 ng/ml). We randomized patients using a 1:1 ratio to receive either two directly observed oral doses of cholecalciferol (300,000 IU) or matching placebo at baseline and 8 weeks. The primary outcome was change in endothelium-dependent brachial artery flow-mediated dilation at 16 weeks. Secondary outcome measures included changes in pulse wave velocity and circulating biomarkers. Cholecalciferol supplementation significantly increased endothelium-dependent brachial artery flow-mediated dilation at 16 weeks, whereas placebo did not (between-group difference in mean change: 5.49%; 95% confidence interval, 4.34% to 6.64%; P vitamin D deficiency, vitamin D supplementation may improve vascular function. This study is registered with the Clinical Trials Registry of India (no.: CTRI/2013/05/003648). Copyright © 2017 by the American Society of Nephrology.

  19. Inflammation-induced lymphangiogenesis and lymphatic dysfunction

    Science.gov (United States)

    Liao, Shan; von der Weid, Pierre-Yves

    2014-01-01

    The lymphatic system is intimately linked to tissue fluid homeostasis and immune cell trafficking. These functions are paramount in the establishment and development of an inflammatory response. In the past decade, an increasing number of reports has revealed that marked changes, such as lymphangiogenesis and lymphatic contractile dysfunction occur in both vascular and nodal parts of the lymphatic system during inflammation, as well as other disease processes. This review provides a critical update on the role of the lymphatic system in disease process such as chronic inflammation and cancer and examines the changes in lymphatic functions the diseases cause and the influence these changes have on the progression of the diseases. PMID:24449090

  20. Influence of Decreased Thyroid Function on the Clinical Course and Occurrence of Vascular Complications of Diabetes Mellitus Type 2

    Directory of Open Access Journals (Sweden)

    Ye.S. Krutikov

    2014-04-01

    Full Text Available The article studies the clinical course and characteristics of vascular complications in patients with diabetes mellitus type 2 on a background of diminished thyroid function. We analyzed the prevalence and severity of diabetic retinopathy, angiopathy of lower extremities vessels and nephropathy in patients with concomitant hypothyroidism of various degrees. It was established that patients with diabetes type 2 had significantly higher severity of vascular complications on the background of both manifest and subclinical hypothyroidism.

  1. Lipoprotein particle number and size predict vascular structure and function better than traditional lipids in adolescents and young adults.

    Science.gov (United States)

    Urbina, Elaine M; McCoy, Connie E; Gao, Zhiqian; Khoury, Philip R; Shah, Amy S; Dolan, Lawrence M; Kimball, Thomas R

    In adults, dyslipidemia is associated with higher carotid thickness and arterial stiffness, predictors of cardiovascular events. In young subjects, lipid concentrations have not been consistently associated with vascular measures. The objective of the study was to compare nuclear magnetic resonance (NMR) measures of lipoprotein particle number (low-density lipoprotein [LDL] particle, low-density lipoprotein [HDL] particle, very low-density lipoprotein [VLDL] particle) and size (LDL size, HDL size, and VLDL size) to determine if they were associated with vascular measures more strongly than lipid concentrations (LDL cholesterol, HDL cholesterol, and triglyceride [TG]). We evaluated 214 lean (L), 228 obese (O), and 214 diabetic (T2DM) subjects aged 10 to 24 years (33% male and 39% Caucasian). Cardiovascular risk factors, vascular structure, and arterial stiffness were measured. General linear models were constructed including demographics, risk factors, and traditional or NMR lipid parameters. A composite vascular function score was developed as the outcome in receiver operator characteristic scores for determining which lipid parameter was superior in predicting vascular damage. Risk factors worsened from L to O to T. However, LDL cholesterol was similar in O and T, whereas LDL size differentiated the 3 groups (T > O > L, P ≤ .0001). Models demonstrated the superiority of NMR values, which entered for all but 1 vascular outcome and explained more of the variance than traditional lipid concentrations. Receiver operator characteristic curves demonstrated that NMR values were superior in predicting vascular outcomes. Models stratified by race were similar but cutpoints predicting vascular outcomes differed by race for TG, TG/HDL, and VLDL. Lipoprotein particle number and size are more strongly related to vascular structure and function than traditional lipid values. NMR lipid measures may be a better indicator of risk for target organ damage than traditional

  2. Differential Effects of Sepsis and Chronic Inflammation on Diaphragm Muscle Fiber Type, Thyroid Hormone Metabolism, and Mitochondrial Function

    NARCIS (Netherlands)

    Bloise, Flavia F.; van der Spek, Anne H.; Surovtseva, Olga V.; Ortiga-Carvalho, Tania Maria; Fliers, Eric; Boelen, Anita

    2016-01-01

    The diaphragm is the main respiratory muscle, and its function is compromised during severe illness. Altered local thyroid hormone (TH) metabolism may be a determinant of impaired muscle function during illness. This study investigates the effects of bacterial sepsis and chronic inflammation on

  3. Effect of Aggressive lipid-lowering treatment with Rosuvastatin on vascular endoTHelium function: evaluation of vascular endothelium function (EARTH study).

    Science.gov (United States)

    Takayama, Tadateru; Hiro, Takafumi; Yoda, Shunichi; Fukamachi, Daisuke; Haruta, Hironori; Kogo, Takaaki; Mineki, Takashi; Murata, Hironobu; Oshima, Toru; Hirayama, Atsushi

    2017-12-05

    Vascular endothelial dysfunction plays an important role in the process of atherosclerosis up to the final stage of plaque rupture. Vascular endothelial dysfunction is reversible, and can be recovered by medications and life-style changes. Improvement in endothelial function may reduce cardiovascular events and improve long-term prognosis. A total of 50 patients with stable angina and dyslipidemia were enrolled, including patients who had not received prior treatment with statins and had serum LDL-C levels ≥ 100 mg/dL, and patients who had previously received statin treatment. All agreed to register regardless of their LDL-C level. Rosuvastatin was initially administered at a dose of 2.5 mg and appropriately titrated up to the maximum dose of 20 mg or until LDL-C levels lower than 80 mg/dL were achieved, for 24 weeks. Endothelial function was assessed by the reactive hyperemia peripheral arterial tonometry (RH-PAT) index in the radial artery by Endo-PAT® 2000 (Endo-PAT®2000, software version 3.0.4, Itamar Medical Ltd., Caesarea, Israel). RH-PAT data were digitally analyzed online by Endo-PAT®2000 at baseline and at 24 weeks. LDL-C and MDA-LDL-C decreased from 112.6 ± 23.3 to 85.5 ± 20.2 mg/dL and from 135.1 ± 36.4 to 113.9 ± 23.5 mg/dL respectively (p < 0.0001). However, HDL-C, hs-CRP and TG did not change significantly after treatment. RH-PAT index levels significantly improved, from 1.60 ± 0.31 to 1.77 ± 0.57 (p = 0.04) after treatment, and the percent change of the RH-PAT index was 12.8 ± 36.9%. Results of multivariate analysis show that serum LDL-C levels over 24 weeks did not act as a predictor of improvement of the RH-PAT index. However, HbA1c at baseline was an independent predictor which influenced the 24-week RH-PAT index level. The RH-PAT index of patients with high HbA1c at baseline did not improve after administration of rosuvastatin but it did improve in patients with low HbA1c at baseline. Aggressive lowering

  4. Cellular function and signaling pathways of vascular smooth muscle cells modulated by sphingosine 1-phosphate

    Directory of Open Access Journals (Sweden)

    Takuji Machida

    2016-12-01

    Full Text Available Sphingosine 1-phosphate (S1P plays important roles in cardiovascular pathophysiology. S1P1 and/or S1P3, rather than S1P2 receptors, seem to be predominantly expressed in vascular endothelial cells, while S1P2 and/or S1P3, rather than S1P1 receptors, seem to be predominantly expressed in vascular smooth muscle cells (VSMCs. S1P has multiple actions, such as proliferation, inhibition or stimulation of migration, and vasoconstriction or release of vasoactive mediators. S1P induces an increase of the intracellular Ca2+ concentration in many cell types, including VSMCs. Activation of S1P3 seems to play an important role in Ca2+ mobilization. S1P induces cyclooxygenase-2 expression in VSMCs via both S1P2 and S1P3 receptors. S1P2 receptor activation in VSMCs inhibits inducible nitric oxide synthase (iNOS expression. At the local site of vascular injury, vasoactive mediators such as prostaglandins and NO produced by VSMCs are considered primarily as a defensive and compensatory mechanism for the lack of endothelial function to prevent further pathology. Therefore, selective S1P2 receptor antagonists may have the potential to be therapeutic agents, in view of their antagonism of iNOS inhibition by S1P. Further progress in studies of the precise mechanisms of S1P may provide useful knowledge for the development of new S1P-related drugs for the treatment of cardiovascular diseases.

  5. Functional Vascular Study in Hypertensive Subjects with Type 2 Diabetes Using Losartan or Amlodipine

    Directory of Open Access Journals (Sweden)

    Cesar Romaro Pozzobon

    2014-07-01

    Full Text Available Background: Antihypertensive drugs are used to control blood pressure (BP and reduce macro- and microvascular complications in hypertensive patients with diabetes. Objectives: The present study aimed to compare the functional vascular changes in hypertensive patients with type 2 diabetes mellitus after 6 weeks of treatment with amlodipine or losartan. Methods: Patients with a previous diagnosis of hypertension and type 2 diabetes mellitus were randomly divided into 2 groups and evaluated after 6 weeks of treatment with amlodipine (5 mg/day or losartan (100 mg/day. Patient evaluation included BP measurement, ambulatory BP monitoring, and assessment of vascular parameters using applanation tonometry, pulse wave velocity (PWV, and flow-mediated dilation (FMD of the brachial artery. Results: A total of 42 patients were evaluated (21 in each group, with a predominance of women (71% in both groups. The mean age of the patients in both groups was similar (amlodipine group: 54.9 ± 4.5 years; losartan group: 54.0 ± 6.9 years, with no significant difference in the mean BP [amlodipine group: 145 ± 14 mmHg (systolic and 84 ± 8 mmHg (diastolic; losartan group: 153 ± 19 mmHg (systolic and 90 ± 9 mmHg (diastolic]. The augmentation index (30% ± 9% and 36% ± 8%, p = 0.025 and augmentation pressure (16 ± 6 mmHg and 20 ± 8 mmHg, p = 0.045 were lower in the amlodipine group when compared with the losartan group. PWV and FMD were similar in both groups. Conclusions: Hypertensive patients with type 2 diabetes mellitus treated with amlodipine exhibited an improved pattern of pulse wave reflection in comparison with those treated with losartan. However, the use of losartan may be associated with independent vascular reactivity to the pressor effect.

  6. A maternal high salt diet disturbs cardiac and vascular function of offspring.

    Science.gov (United States)

    Maruyama, Kana; Kagota, Satomi; Van Vliet, Bruce N; Wakuda, Hirokazu; Shinozuka, Kazumasa

    2015-09-01

    High salt intake is an environmental factor that promotes increased blood pressure. We previously demonstrated that high salt diet causes aggravation of hypertension and impaired vasodilation in response to nitric oxide (NO) in young spontaneously hypertensive rats (SHR), which exhibit low sensitivity to salt in adulthood. Changes in offspring blood pressure and cardiovascular structures have been reported. However, it remains unclear to what extent a maternal high salt intake may affect cardiac and/or vascular function in offspring. Therefore, we investigated influence of exposure to a maternal high salt diet during gestation and lactation on offspring's cardiac and arterial functions in SHR. SHR dams were fed either a high salt diet or a control diet. After weaning, the offspring were fed the high salt diet or control diet for 8weeks. Compared with offspring of control diet-fed dams, at 12weeks of age, offspring of the high-salt diet-fed dams had lower blood pressure, heart rate, indices of both left ventricular systolic and diastolic function, and a decreased aortic vasodilation response to NO. Postnatal high salt intake did not affect blood pressure, vasodilatory response, or cardiac function in offspring of high-salt diet-fed dams. Neither maternal nor postnatal dietary salt altered levels of lipid peroxide, superoxide dismutase, or angiotensinogen mRNA in serum and ventricle of the offspring. Exposure to high maternal dietary salt induces cardiac and vascular dysfunction in offspring. These results point to the possible importance of avoiding excess dietary salt during gestation and lactation. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Role of IL-10 in Resolution of Inflammation and Functional Recovery after Peripheral Nerve Injury.

    Science.gov (United States)

    Siqueira Mietto, Bruno; Kroner, Antje; Girolami, Elizabeth I; Santos-Nogueira, Eva; Zhang, Ji; David, Samuel

    2015-12-16

    A rapid proinflammatory response after peripheral nerve injury is required for clearance of tissue debris (Wallerian degeneration) and effective regeneration. Unlike the CNS, this response is rapidly terminated in peripheral nerves starting between 2 and 3 weeks after crush injury. We examined the expression and role of the anti-inflammatory cytokine IL-10 in the resolution of inflammation and regeneration after sciatic nerve crush injury in mice. IL-10 mRNA increased over the first 7 d after injury, whereas at the protein level, immunofluorescence labeling showed IL-10(+) cells increased almost 3-fold in the first 3 weeks, with macrophages being the major cell type expressing IL-10. The role of IL-10 in nerve injury was assessed using IL-10-null mice. Increased numbers of macrophages were found in the distal segment of IL-10-null mice at early (3 d) and late (14 and 21 d) time points, suggesting that IL-10 may play a role in controlling the early influx and the later efflux of macrophages out of the nerve. A chemokine/cytokine PCR array of the nerve 24 h after crush showed a 2- to 4-fold increase in the expression of 10 proinflammatory mediators in IL-10(-/-) mice. In addition, myelin phagocytosis in vitro by LPS stimulated bone-marrow-derived macrophages from IL-10-null mice failed to downregulate expression of proinflammatory chemokines/cytokines, suggesting that IL-10 is required for the myelin-phagocytosis-induced shift of macrophages from proinflammatory to anti-inflammatory/pro-repair phenotype. The failure to switch off inflammation in IL-10-null mice was accompanied by impaired axon regeneration and poor recovery of motor and sensory function. An appropriately regulated inflammatory response after peripheral nerve injury is essential for axon regeneration and recovery. The aim of this study was to investigate the expression and role of the anti-inflammatory cytokine IL-10 in terminating inflammation after sciatic nerve crush injury and promoting

  8. Extracellular vesicles regulate immune responses and cellular function in intestinal inflammation and repair.

    Science.gov (United States)

    Bui, Triet M; Mascarenhas, Lorraine A; Sumagin, Ronen

    2018-02-02

    Tightly controlled communication among the various resident and recruited cells in the intestinal tissue is critical for maintaining tissue homeostasis, re-establishment of the barrier function and healing responses following injury. Emerging evidence convincingly implicates extracellular vesicles (EVs) in facilitating this important cell-to-cell crosstalk by transporting bioactive effectors and genetic information in healthy tissue and disease. While many aspects of EV biology, including release mechanisms, cargo packaging, and uptake by target cells are still not completely understood, EVs contribution to cellular signaling and function is apparent. Moreover, EV research has already sparked a clinical interest, as a potential diagnostic, prognostic and therapeutic tool. The current review will discuss the function of EVs originating from innate immune cells, namely, neutrophils, monocytes and macrophages, as well as intestinal epithelial cells in healthy tissue and inflammatory disorders of the intestinal tract. Our discussion will specifically emphasize the contribution of EVs to the regulation of vascular and epithelial barrier function in inflamed intestines, wound healing, as well as trafficking and activity of resident and recruited immune cells.

  9. Vitamin D Controls Resistance Artery Function through Regulation of Perivascular Adipose Tissue Hypoxia and Inflammation

    Science.gov (United States)

    Pelham, Christopher J.; Drews, Elizabeth M.; Agrawal, Devendra K.

    2016-01-01

    Vitamin D deficiency in human subjects is associated with hypertension, metabolic syndrome and related risk factors of cardiovascular diseases. Serum 25-hydroxyvitamin D levels correlate inversely with adiposity in obese and lean individuals. Bioactive vitamin D, or calcitriol, exerts anti-inflammatory effects on adipocytes, preadipocytes and macrophages in vitro. We tested the hypothesis that vitamin D deficiency alters the phenotype of perivascular adipose tissue (PVAT) leading to impaired function in resistance artery. To examine the effects of vitamin D and PVAT on vascular reactivity, myograph experiments were performed on arteries, with or without intact PVAT, from mice maintained on vitamin D-deficient, vitamin D-sufficient or vitamin D-supplemented diet. Systolic blood pressure was significantly increased in mice on vitamin D-deficient diet. Importantly, vitamin D deficiency enhanced angiotensin II-induced vasoconstriction and impaired the normal ability of PVAT to suppress contractile responses of the underlying mesenteric resistance artery to angiotensin II and serotonin. Furthermore, vitamin D deficiency caused upregulation of the mRNA expression of tumor necrosis factor-α, hypoxia-inducible factor-1α and its downstream target lysyl oxidase in mesenteric PVAT. Incubation of mesenteric arteries under hypoxic conditions impaired the anti-contractile effects of intact PVAT on those arteries from mice on vitamin D-sufficient diet. Vitamin D supplementation protected arteries against hypoxia-induced impairment of PVAT function. The protective effects of vitamin D against vascular dysfunction, hypertension and cardiovascular diseases may be mediated, at least in part, through regulation of inflammatory and hypoxia signaling pathways in PVAT. PMID:27374117

  10. Functional significance of macrophage-derived exosomes in inflammation and pain.

    Science.gov (United States)

    McDonald, Marguerite K; Tian, Yuzhen; Qureshi, Rehman A; Gormley, Michael; Ertel, Adam; Gao, Ruby; Aradillas Lopez, Enrique; Alexander, Guillermo M; Sacan, Ahmet; Fortina, Paolo; Ajit, Seena K

    2014-08-01

    Exosomes, secreted microvesicles transporting microRNAs (miRNAs), mRNAs, and proteins through bodily fluids, facilitate intercellular communication and elicit immune responses. Exosomal contents vary, depending on the source and the physiological conditions of cells, and can provide insights into how cells and systems cope with physiological perturbations. Previous analysis of circulating miRNAs in patients with complex regional pain syndrome (CRPS), a debilitating chronic pain disorder, revealed a subset of miRNAs in whole blood that are altered in the disease. To determine functional consequences of alterations in exosomal biomolecules in inflammation and pain, we investigated exosome-mediated information transfer in vitro, in a rodent model of inflammatory pain, and in exosomes from patients with CRPS. Mouse macrophage cells stimulated with lipopolysaccharides secrete exosomes containing elevated levels of cytokines and miRNAs that mediate inflammation. Transcriptome sequencing of exosomal RNA revealed global alterations in both innate and adaptive immune pathways. Exosomes from lipopolysaccharide-stimulated cells were sufficient to cause nuclear factor-κB activation in naive cells, indicating functionality in recipient cells. A single injection of exosomes attenuated thermal hyperalgesia in a murine model of inflammatory pain, suggesting an immunoprotective role for macrophage-derived exosomes. Macrophage-derived exosomes carry a protective signature that is altered when secreting cells are exposed to an inflammatory stimulus. We also show that circulating miRNAs altered in patients with complex regional pain syndrome are trafficked by exosomes. With their systemic signaling capabilities, exosomes can induce pleiotropic effects potentially mediating the multifactorial pathology underlying chronic pain, and should be explored for their therapeutic utility. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights

  11. Candesartan Attenuates Diabetic Retinal Vascular Pathology by Restoring Glyoxalase-I Function

    Science.gov (United States)

    Miller, Antonia G.; Tan, Genevieve; Binger, Katrina J.; Pickering, Raelene J.; Thomas, Merlin C.; Nagaraj, Ram H.; Cooper, Mark E.; Wilkinson-Berka, Jennifer L.

    2010-01-01

    OBJECTIVE Advanced glycation end products (AGEs) and the renin-angiotensin system (RAS) are both implicated in the development of diabetic retinopathy. How these pathways interact to promote retinal vasculopathy is not fully understood. Glyoxalase-I (GLO-I) is an enzyme critical for the detoxification of AGEs and retinal vascular cell survival. We hypothesized that, in retina, angiotensin II (Ang II) downregulates GLO-I, which leads to an increase in methylglyoxal-AGE formation. The angiotensin type 1 receptor blocker, candesartan, rectifies this imbalance and protects against retinal vasculopathy. RESEARCH DESIGN AND METHODS Cultured bovine retinal endothelial cells (BREC) and bovine retinal pericytes (BRP) were incubated with Ang II (100 nmol/l) or Ang II+candesartan (1 μmol/l). Transgenic Ren-2 rats that overexpress the RAS were randomized to be nondiabetic, diabetic, or diabetic+candesartan (5 mg/kg/day) and studied over 20 weeks. Comparisons were made with diabetic Sprague-Dawley rats. RESULTS In BREC and BRP, Ang II induced apoptosis and reduced GLO-I activity and mRNA, with a concomitant increase in nitric oxide (NO•), the latter being a known negative regulator of GLO-I in BRP. In BREC and BRP, candesartan restored GLO-I and reduced NO•. Similar events occurred in vivo, with the elevated RAS of the diabetic Ren-2 rat, but not the diabetic Sprague-Dawley rat, reducing retinal GLO-I. In diabetic Ren-2 rats, candesartan reduced retinal acellular capillaries, inflammation, and inducible nitric oxide synthase and NO•, and restored GLO-I. CONCLUSIONS We have identified a novel mechanism by which candesartan improves diabetic retinopathy through the restoration of GLO-I. PMID:20852029

  12. Effects of Kaempferia parviflora rhizomes dichloromethane extract on vascular functions in middle-aged male rat.

    Science.gov (United States)

    Yorsin, Somruedee; Kanokwiroon, Kanyanatt; Radenahmad, Nisaudah; Jansakul, Chaweewan

    2014-10-28

    In Thai traditional medicine, rhizomes of Kaempferia parviflora (KP) have been used for treating hypertension and for the promotion of longevity with good health and well being. Ageing is one of the most important risk factors for development of cardiovascular disease. To investigate whether a 6 weeks oral administration of a dichloromethane extract of fresh rhizomes of Kaempferia parviflora (KPD) had any effects on vascular functions, on the accumulation of lipid, as well as on any signs of gross organ toxicity in middle-aged rats. Fresh rhizomes of Kaempferia parviflora were first macerated twice with 95% ethanol to remove the dark color before extracting three times with 100% dichloromethane. The dichloromethane extract was evaporated under reduced pressure to obtain the dried Kaempferia parviflora dichloromethane extract (KPD). The rats were orally administered with the KPD at a dosage of 100mg/kg body weight, or with the same volume of the vehicle (tween 80, 0.2g: carboxy-methylcellulose sodium, 0.2g: distilled water 10 ml) once or twice a day for 6 weeks. Vascular functions were studied on isolated thoracic aorta and the mesenteric artery. The vascular eNOS enzyme was measured by Western blot analysis. Blood chemistry was measured by enzymatic methods. Liver cell lipid accumulation was measured using oil red O staining. A 6 weeks treatment of KPD once a day had no significant effects on any of the studied parameters. When the KPD was given twice a day, the contractile responses to phenylephrine of the thoracic aorta and mesenteric artery were lower than the vehicle control group, and this effect was abolished by N(G)-nitro-l-arginine or by removal of the vascular endothelium. Vasorelaxation to acetylcholine, but not to glyceryl trinitrate, by the thoracic aortic and mesenteric ring precontracted with phenylephrine was higher from the KPD treated rats than those from the vehicle control groups. Western blot analysis showed a higher quantity of thoracic- and

  13. White matter hyperintensities, executive function and global cognitive performance in vascular mild cognitive impairment

    Directory of Open Access Journals (Sweden)

    Felipe Kenji Sudo

    2013-07-01

    Full Text Available Vascular mild cognitive impairment (VaMCI represents an early symptomatic stage of vascular cognitive impairment and might be associated to fronto-executive dysfunction. Methods Twenty-six individuals (age: 73.11±7.90 years; 65.4% female; schooling: 9.84±3.61 years were selected through neuropsychological assessment and neuroimaging. Clinical and neuroimaging data of VaMCI individuals (n=15 were compared to normal controls (NC, n=11 and correlated with Fazekas scale. Results VaMCI performed significantly worse than NC in Trail-Making Test (TMT B, errors in TMT B, difference TMT B-A and Cambridge Cognitive Examination (CAMCOG final scores. Correlations were found among scores in modified Fazekas scale and performances in TMT B (time to complete and errors, difference TMT B-A and CAMCOG total score. Conclusion Extension of white matter hyperintensities might be correlated to poorer global cognition and impairments in a set of fronto-executive functions, such as cognitive speed, set shifting and inhibitory control in VaMCI.

  14. The relationship between adrenomedullin, metabolic factors, and vascular function in individuals with type 2 diabetes.

    Science.gov (United States)

    Lim, Su Chi; Morgenthaler, Nils G; Subramaniam, Tavintharan; Wu, Yew Seng; Goh, Siew Kheng; Sum, Chee Fang

    2007-06-01

    Subjects with type 2 diabetes are at risk for vascular injury. Several vasoactive factors (e.g., angiotensin) have been implicated. We hypothesize that adrenomedullin, a novel vascoactive factor, is deranged in subjects with type 2 diabetes. Using a new immunoluminometric method, plasma midregional proadrenomedullin (MR-proADM) was measured in four groups of Chinese subjects: healthy (n = 100, fasting plasma glucose [FPG] RCMP) was quantified in vivo using 2-dimensional laser Doppler flowmetry. We investigated the relationship between plasma MR-proADM concentrations, multiple metabolic factors, and vascular function. We observed a stepwise increase in MR-proADM among the groups: healthy group mean +/- SD 0.27 +/- 0.09, IFG group 0.29 +/- 0.13, diabetic group 0.42 +/- 0.13, and diabetic nephropathy group 0.81 +/- 0.54 nmol/l (diabetic vs. healthy and IFG groups, P = 0.04; and diabetic nephropathy group vs. all, P RCMP (r = 0.43, P = 0.002). Plasma MR-proADM concentration was elevated in subjects with type 2 diabetes. This was further accentuated when nephropathy set in. MR-proADM was related to multiple metabolic factors and basal microcirculatory perfusion. Adrenomedullin might play a role in the pathogenesis of diabetic vasculopathy.

  15. Cartilage damage and bone erosion are more prominent determinants of functional impairment in longstanding experimental arthritis than synovial inflammation

    Directory of Open Access Journals (Sweden)

    Silvia Hayer

    2016-11-01

    Full Text Available Chronic inflammation of articular joints causing bone and cartilage destruction consequently leads to functional impairment or loss of mobility in affected joints from individuals affected by rheumatoid arthritis (RA. Even successful treatment with complete resolution of synovial inflammatory processes does not lead to full reversal of joint functionality, pointing to the crucial contribution of irreversibly damaged structural components, such as bone and cartilage, to restricted joint mobility. In this context, we investigated the impact of the distinct components, including synovial inflammation, bone erosion or cartilage damage, as well as the effect of blocking tumor necrosis factor (TNF on functional impairment in human-TNF transgenic (hTNFtg mice, a chronic inflammatory erosive animal model of RA. We determined CatWalk-assisted gait profiles as objective quantitative measurements of functional impairment. We first determined body-weight-independent gait parameters, including maximum intensity, print length, print width and print area in wild-type mice. We observed early changes in those gait parameters in hTNFtg mice at week 5 – the first clinical signs of arthritis. Moreover, we found further gait changes during chronic disease development, indicating progressive functional impairment in hTNFtg mice. By investigating the association of gait parameters with inflammation-mediated joint pathologies at different time points of the disease course, we found a relationship between gait parameters and the extent of cartilage damage and bone erosions, but not with the extent of synovitis in this chronic model. Next, we observed a significant improvement of functional impairment upon blocking TNF, even at progressed stages of disease. However, blocking TNF did not restore full functionality owing to remaining subclinical inflammation and structural microdamage. In conclusion, CatWalk gait analysis provides a useful tool for quantitative

  16. Computationally efficient vascular input function models for quantitative kinetic modelling using DCE-MRI

    Energy Technology Data Exchange (ETDEWEB)

    Orton, Matthew R; D' Arcy, James A; Walker-Samuel, Simon; Collins, David J; Leach, Martin O [Cancer Research UK Clinical MR Research Group, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, Surrey SM2 5PT (United Kingdom); Hawkes, David J; Atkinson, David [Centre for Medical Image Computing, University College London, WC1E 6BT (United Kingdom)

    2008-03-07

    A description of the vascular input function is needed to obtain tissue kinetic parameter estimates from dynamic contrast enhanced MRI (DCE-MRI) data. This paper describes a general modelling framework for defining compact functional forms to describe vascular input functions. By appropriately specifying the components of this model it is possible to generate models that are realistic, and that ensure that the tissue concentration curves can be analytically calculated. This means that the computations necessary to estimate parameters from measured data are relatively efficient, which is important if such methods are to become of use in clinical practice. Three models defined by four parameters, using exponential, gamma-variate and cosine descriptions of the bolus, are described and their properties investigated using simulations. The results indicate that if there is no plasma fraction, then the proposed models are indistinguishable. When a small plasma fraction is present the exponential model gives parameter estimates that are biassed by up to 50%, while the other two models give very little bias; up to 10% but less than 5% in most cases. With a larger plasma fraction the exponential model is again biassed, the gamma-variate model has a small bias, but the cosine model has a very little bias and is indistinguishable from the model used to generate the data. The computational speed of the analytic approaches is compared with a fast-Fourier-transform-based numerical convolution approach. The analytic methods are nearly 10 times faster than the numerical methods for the isolated computation of the convolution, and around 4-5 times faster when used in an optimization routine to obtain parameter estimates. These results were obtained from five example data sets, one of which was examined in more detail to compare the estimates obtained using the different models, and with literature values.

  17. Do acute effects of exercise on vascular function predict adaptation to training?

    Science.gov (United States)

    Dawson, Ellen A; Cable, N Timothy; Green, Daniel J; Thijssen, Dick H J

    2018-03-01

    No previous study has explored the importance of exercise-induced changes in vascular function to prolonged adaptations. Therefore, the purpose was to explore the within-subject relationship between the acute post-exercise change in brachial artery endothelial function (flow-mediated dilation, FMD) and the change in resting FMD after a 2-week exercise training in healthy volunteers. Twenty one healthy, young men (24 ± 5 years) underwent assessment of brachial artery FMD using high-resolution ultrasound before and after 30-min of moderate-intensity cycle exercise (80% maximal heart rate). Subsequently, subjects performed five 30-min cycle exercise bouts at 80% maximal heart rate across a 2-week period, followed by repeat assessment of resting brachial FMD post-training. Correcting for changes in diameter and shear, FMD did not change after the initial exercise bout (P = 0.26). However, a significant correlation was found between post-exercise changes in FMD and adaptation in resting FMD after training (r = 0.634, P = 0.002), where an acute decrease in post-exercise FMD resulted in a decrease in baseline FMD after 2 weeks and vice versa. We also found a positive correlation between antegrade shear rate during exercise and change in FMD% after acute exercise and after exercise training (r = 0.529 and 0.475, both P < 0.05). Our findings suggest that acute post-exercise changes in vascular function are related to changes in resting FMD after a 2-week endurance exercise training period in healthy men, an effect that may be related to exercise-induced increases in antegrade shear rate. This provides further insight into the relevance of acute changes in shear and FMD for subsequent adaptation.

  18. Keratin-associated protein 5-5 controls cytoskeletal function and cancer cell vascular invasion.

    Science.gov (United States)

    Berens, E B; Sharif, G M; Schmidt, M O; Yan, G; Shuptrine, C W; Weiner, L M; Glasgow, E; Riegel, A T; Wellstein, A

    2017-02-02

    Cancer cell vascular invasion is a crucial step in the malignant progression toward metastasis. Here we used a genome-wide RNA interference screen with E0771 mammary cancer cells to uncover drivers of endothelial monolayer invasion. We identified keratin-associated protein 5-5 (Krtap5-5) as a candidate. Krtap5-5 belongs to a large protein family that is implicated in crosslinking keratin intermediate filaments during hair formation, yet these Krtaps have no reported role in cancer. Depletion of Krtap5-5 from cancer cells led to cell blebbing and a loss of keratins 14 and 18, in addition to the upregulation of vimentin intermediate filaments. This intermediate filament subtype switching induced dysregulation of the actin cytoskeleton and reduced the expression of hemidesmosomal α6/β4-integrins. We further demonstrate that knockdown of keratin 18 phenocopies the loss of Krtap5-5, suggesting that Krtap5-5 crosstalks with keratin 18 in E0771 cells. Disruption of the keratin cytoskeleton by perturbing Krtap5-5 function broadly altered the expression of cytoskeleton regulators and the localization of cell surface markers. Krtap5-5 depletion did not impact cell viability but reduced cell motility and extracellular matrix invasion, as well as extravasation of cancer cells into tissues in zebrafish and mice. We conclude that Krtap5-5 is a previously unknown regulator of cytoskeletal function in cancer cells that modulates motility and vascular invasion. Thus, in addition to its physiologic function, a Krtap can serve as a switch toward malignant progression.

  19. Fetal growth is associated with first-trimester maternal vascular function.

    Science.gov (United States)

    Iacobaeus, C; Kahan, T; Jörneskog, G; Bremme, K; Thorsell, M; Andolf, E

    2016-10-01

    To investigate the relationship between maternal endothelial function in the first trimester, assessed in both the brachial artery and the forearm skin microcirculation, and fetal growth. Vascular function was assessed in 56 pregnant women during gestational weeks 11-14. Vascular reactivity in the brachial artery was evaluated by postischemic hyperemia-induced flow-mediated vasodilatation (FMD) and by vasodilatation following administration of sublingual glyceryl trinitrate (GTN). Forearm skin microcirculation was investigated by laser Doppler perfusion imaging during iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) to assess endothelium-dependent and -independent microvascular vasodilatation, respectively. Fetal growth was measured at study inclusion and birth-weight centile was calculated after delivery. FMD and GTN-induced vasodilatation were both associated with birth-weight centile. On multivariate analysis (adjusted for brachial artery diameter at rest, blood pressure, maternal age and heart rate), for FMD β = 1.7 (95% CI, 0.06-3.34), r 2  = 0.26 and P = 0.042, and for GTN-induced vasodilatation β = 2.6 (95% CI, 0.44-4.68), r 2  = 0.15 and P = 0.02. Endothelium-dependent and -independent microvascular reactivity were also associated with birth-weight centile: for ACh β = 7.82 (95% CI, 1.81-13.83), r 2  = 0.12 and P = 0.029, and for SNP β = 6.27 (95% CI, 1.20-11.34), r 2  = 0.11 and P = 0.016. First-trimester maternal vascular dilatation capacity (rather than endothelial function alone) is associated with fetal growth. These findings were consistent in both the brachial artery and the forearm skin microcirculation. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

  20. The Association of Long-Functioning Hemodialysis Vascular Access with Prevalence of Left Ventricular Hypertrophy in Kidney Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Aureliusz Kolonko

    2014-01-01

    Full Text Available Left ventricular hypertrophy (LVH is frequently observed in chronic dialysis patients and is also highly prevalent in kidney transplant recipients. This study evaluates the impact of long-functioning hemodialysis vascular access on LVH in single center cohort of kidney transplant recipients. 162 patients at 8.7 ± 1.8 years after kidney transplantation were enrolled. Echocardiography, carotid ultrasound, and assessment of pulse wave velocity were performed. LVH was defined based on left ventricular mass (LVM indexed for body surface area (BSA and height2.7. There were 67 patients with and 95 without patent vascular access. Both study groups were comparable with respect to gender, age, duration of dialysis therapy, and time after transplantation, kidney graft function, and cardiovascular comorbidities. Patients with patent vascular access were characterized by significantly elevated LVM and significantly greater percentage of LVH, based on LVMI/BSA (66.7 versus 48.4%, P=0.02. OR for LVH in patients with patent vascular access was 2.39 (1.19–4.76, P=0.01. Regression analyses confirmed an independent contribution of patent vascular access to higher LVM and increased prevalence of LVH. We concluded that long-lasting patent hemodialysis vascular access after kidney transplantation is associated with the increased prevalence of LVH in kidney transplant recipients.

  1. Transarterial chemo-embolisation of hepatocellular carcinoma: impact of liver function and vascular invasion

    Science.gov (United States)

    Waked, Imam; Berhane, Sarah; Toyoda, Hidenori; Chan, Stephen L; Stern, Nicholas; Palmer, Daniel; Tada, Toshifumi; Yeo, Winnie; Mo, Frankie; Bettinger, Dominik; Kirstein, Martha M; Iñarrairaegui, Mercedes; Gomaa, Asmaa; Vogel, Arndt; Meyer, Tim; Sangro, Bruno; Lai, Paul; Kumada, Takashi; Johnson, Philip J

    2017-01-01

    Background: Transarterial chemo-embolisation (TACE) is recommended for patients with BCLC intermediate stage hepatocellular carcinoma (stage B), particularly in patients with good underlying liver function and minimal symptoms. The hepatoma arterial embolisation prognostic (HAP) score combines measures of liver function and tumour-related factors to offer a simple prognostic scoring system. The Albumin-Bilirubin (ALBI) grade permits assessment of the impact of liver function on survival. We aimed to investigate these two models and vascular invasion (VI). Methods: In an international cohort of 3030 patients undergoing TACE, we examined the impact of liver function as assessed by the ALBI score, the HAP score and VI on survival. Results: Classification according to ALBI grade resulted in non-overlapping survival curves in the overall data set and all regional cohorts. The HAP score was also validated. Tumour number, aetiology and VI were identified as additional independent prognostic risk factors not currently included in the HAP score. Survival was particularly poor for patients with VI. Conclusions: The ALBI grade categorised patients receiving TACE into three clear prognostic groups, thereby emphasising the importance of underlying liver function in the outcome of TACE. The HAP score has been validated internationally and the serious adverse impact of VI is clearly shown. PMID:28125820

  2. Physical activity, immune function and inflammation in kidney patients (the PINK study): a feasibility trial protocol.

    Science.gov (United States)

    Highton, Patrick James; Neale, Jill; Wilkinson, Thomas J; Bishop, Nicolette C; Smith, Alice C

    2017-05-29

    Patients with chronic kidney disease (CKD) display increased infection-related mortality and elevated cardiovascular risk only partly attributed to traditional risk factors. Patients with CKD also exhibit a pro-inflammatory environment and impaired immune function. Aerobic exercise has the potential to positively impact these detriments, but is under-researched in this patient population. This feasibility study will investigate the effects of acute aerobic exercise on inflammation and immune function in patients with CKD to inform the design of larger studies intended to ultimately influence current exercise recommendations. Patients with CKD, including renal transplant recipients, will visit the laboratory on two occasions, both preceded by appropriate exercise, alcohol and caffeine restrictions. On visit 1, baseline assessments will be completed, comprising anthropometrics, body composition, cardiovascular function and fatigue and leisure time exercise questionnaires. Participants will then undertake an incremental shuttle walk test to estimate predicted peak O 2 consumption (VO 2 peak). On visit 2, participants will complete a 20 min shuttle walk at a constant speed to achieve 85% estimated VO 2 peak. Blood and saliva samples will be taken before, immediately after and 1 hour after this exercise bout. Muscle O 2 saturation will be monitored throughout exercise and recovery. Age and sex-matched non-CKD 'healthy control' participants will complete an identical protocol. Blood and saliva samples will be analysed for markers of inflammation and immune function, using cytometric bead array and flow cytometry techniques. Appropriate statistical tests will be used to analyse the data. A favourable opinion was granted by the East Midlands-Derby Research Ethics Committee on 18 September 2015 (ref 15/EM/0391), and the study was approved and sponsored by University Hospitals of Leicester Research and Innovation (ref 11444). The study was registered with ISRCTN (ref

  3. Irbesartan and lipoic acid improve endothelial function and reduce markers of inflammation in the metabolic syndrome: results of the Irbesartan and Lipoic Acid in Endothelial Dysfunction (ISLAND) study

    National Research Council Canada - National Science Library

    Sola, Srikanth; Mir, Muhammad Q S; Cheema, Faiz A; Khan-Merchant, Nadya; Menon, Rekha G; Parthasarathy, Sampath; Khan, Bobby V

    2005-01-01

    .... We evaluated the ability of irbesartan, an angiotensin receptor blocker, and lipoic acid, an antioxidant, to affect endothelial function and inflammation in patients with the metabolic syndrome...

  4. Periodontal inflammation in relation to cognitive function in an older adult Danish population.

    Science.gov (United States)

    Kamer, Angela R; Morse, Douglas E; Holm-Pedersen, Poul; Mortensen, Erik L; Avlund, Kirsten

    2012-01-01

    Inflammation plays a significant role in Alzheimer's disease (AD) pathogenesis. Studies have shown that systemic, peripheral infections affect AD patients. Cognitive dysfunction is a consistent finding in AD and periodontal disease is a chronic, peripheral infection often resulting in tooth loss. We hypothesized that older adults with periodontal inflammation (PI) or many missing teeth would show impaired cognition compared to subjects without PI or with few missing teeth, and among subjects with PI, those with many missing teeth would show impaired cognition compared to those with few missing teeth. The effect of PI/tooth loss on cognitive function [measured by Digit Symbol (DST) and Block Design (BDT) tests] was assessed in 70-year old Danish subjects. We found: 1) subjects with PI obtained lower mean DST scores compared to subjects without PI (p < 0.05); 2) subjects with many missing teeth had lower mean DST and BDT scores compared to subjects with few missing teeth (p < 0.05); 3) the association of PI with DST and BDT scores was dependant on the number of missing teeth (interaction: p = 0.03 and p = 0.06); and 4) education and previous cognitive scores (age 50) were important covariates. Subjects with PI had significantly lower adjusted mean DST scores compared to subjects without PI. However for adjusted BDT, the significance held only for subjects with few missing teeth. No difference in the adjusted DST and BDT scores was seen between subjects with many missing teeth compared to those with few missing teeth. These results support the hypothesis that PI may affect cognition.

  5. Genistein prevents hyperglycemia-induced monocyte adhesion to human aortic endothelial cells through preservation of the cAMP signaling pathway and ameliorates vascular inflammation in obese diabetic mice.

    Science.gov (United States)

    Babu, Pon Velayutham Anandh; Si, Hongwei; Fu, Zhuo; Zhen, Wei; Liu, Dongmin

    2012-04-01

    Hyperglycemia-induced vascular inflammation resulting in the enhanced monocyte-endothelial cell (EC) interaction is the key event in the pathogenesis of atherosclerosis in diabetes. Here, we investigated the effect of isoflavone genistein on hyperglycemia-stimulated vascular inflammation. Human aortic EC (HAEC) were pretreated with genistein before the addition of high glucose (HG; 25 mmol/L) for 48 h. Genistein at a physiological concentration (0.1 μmol/L) significantly inhibited HG-induced adhesion of monocytes to HAEC and suppressed endothelial production of monocyte chemotactic protein-1 (MCP-1) and IL-8. Inhibition of adenylate cyclase or protein kinase A (PKA) significantly attenuated the antiadhesion effect of genistein. Consistently, genistein improved HG-impaired intracellular cAMP production and PKA activity in HAEC. Six-week-old diabetic db/db mice were untreated (db/db) or treated with a diet containing 1 g genistein/kg diet (db/db+G) for 8 wk. Their nondiabetic db/+ mice were used as normal controls. Circulating concentrations of MCP-1/JE and KC were significantly greater, whereas IL-10 concentrations were lower in db/db mice than those in normal mice. Dietary supplementation of genistein did not normalize but significantly suppressed the elevated serum concentrations of MCP-1/JE from 286 ± 30 ng/L to 181 ± 35 ng/L and KC from 321 ± 21 ng/L to 232 ± 20 ng/L while increasing that of IL-10 from 35 ± 4 ng/L to 346 ± 35 ng/L in db/db+G mice. Further, genistein treatment suppressed diabetes-induced adhesion of monocytes to EC by 87% and endothelial secretion of adhesion molecules. We conclude that genistein improves diabetes-caused vascular inflammation, which may be mediated through promoting the cAMP/PKA pathway.

  6. Genistein Prevents Hyperglycemia-Induced Monocyte Adhesion to Human Aortic Endothelial Cells through Preservation of the cAMP Signaling Pathway and Ameliorates Vascular Inflammation in Obese Diabetic Mice123

    Science.gov (United States)

    Babu, Pon Velayutham Anandh; Si, Hongwei; Fu, Zhuo; Zhen, Wei; Liu, Dongmin

    2012-01-01

    Hyperglycemia-induced vascular inflammation resulting in the enhanced monocyte-endothelial cell (EC) interaction is the key event in the pathogenesis of atherosclerosis in diabetes. Here, we investigated the effect of isoflavone genistein on hyperglycemia-stimulated vascular inflammation. Human aortic EC (HAEC) were pretreated with genistein before the addition of high glucose (HG; 25 mmol/L) for 48 h. Genistein at a physiological concentration (0.1 μmol/L) significantly inhibited HG-induced adhesion of monocytes to HAEC and suppressed endothelial production of monocyte chemotactic protein-1 (MCP-1) and IL-8. Inhibition of adenylate cyclase or protein kinase A (PKA) significantly attenuated the antiadhesion effect of genistein. Consistently, genistein improved HG-impaired intracellular cAMP production and PKA activity in HAEC. Six-week-old diabetic db/db mice were untreated (db/db) or treated with a diet containing 1 g genistein/kg diet (db/db+G) for 8 wk. Their nondiabetic db/+ mice were used as normal controls. Circulating concentrations of MCP-1/JE and KC were significantly greater, whereas IL-10 concentrations were lower in db/db mice than those in normal mice. Dietary supplementation of genistein did not normalize but significantly suppressed the elevated serum concentrations of MCP-1/JE from 286 ± 30 ng/L to 181 ± 35 ng/L and KC from 321 ± 21 ng/L to 232 ± 20 ng/L while increasing that of IL-10 from 35 ± 4 ng/L to 346 ± 35 ng/L in db/db+G mice. Further, genistein treatment suppressed diabetes-induced adhesion of monocytes to EC by 87% and endothelial secretion of adhesion molecules. We conclude that genistein improves diabetes-caused vascular inflammation, which may be mediated through promoting the cAMP/PKA pathway. PMID:22399524

  7. Acute black tea consumption improves cutaneous vascular function in healthy middle-aged humans.

    Science.gov (United States)

    Woodward, Kirsty A; Hopkins, Nicola D; Draijer, Richard; de Graaf, Young; Low, David A; Thijssen, Dick H J

    2016-12-22

    Dietary flavonoids, such as those present in black tea, are associated with reduced risk of cardiovascular disease (CVD), possibly through improving nitric oxide (NO) mediated vascular function. The aim of this study was to examine the effect of acute black tea ingestion on cutaneous microvascular function. Twenty healthy participants (58 ± 5 y, 9 men) attended two experimental trials (tea, placebo), 7-days apart in a randomised, controlled, double-blind, cross-over design. Participants ingested a single dose of 200 ml black tea or placebo, followed by assessment of forearm cutaneous perfusion using laser-Doppler flowmetry (LDF) using three distinct heating protocols, enabling us to distinguish between axon- and endothelium-dependent vasodilation: 1. rapid 42°C, 2. rapid 39°C and 3. gradual 42°C. On the contralateral arm, full-field laser perfusion imaging (FLPI) was used to assess forearm perfusion during gradual 42°C. Data were presented as cutaneous vascular conductance (CVC; flux/mean arterial pressure, MAP) and CVC expressed as a percentage of maximal CVC (%CVCmax). Rapid local heating to 39°C or 42°C demonstrated no effect of tea for flux, CVC or %CVCmax (all P > 0.05). Gradual local heating to 42 °C, however, produced a higher skin blood flow following black tea ingestion for absolute CVC (P = 0.04) when measured by LDF, and higher absolute flux (P < 0.001) and CVC (P < 0.001) measured with FLPI. No effect of tea was found for %CVCmax when assessed by either LDF or FLPI. Acute tea ingestion enhanced cutaneous vascular responses to gradual local heating to 42 °C in healthy, middle-aged participants, possibly through a mechanism related to activation of endothelium-derived chemical mediators, such as NO. These improvements may contribute to the cardiovascular health benefits of regular tea ingestion. Copyright © 2016. Published by Elsevier Ltd.

  8. Association of cardio-ankle vascular index with diastolic heart function in hypertensive patients.

    Science.gov (United States)

    Kim, Hyungseop; Kim, Hye-Soon; Yoon, Hyuck-Jun; Park, Hyoung-Seob; Cho, Yun-Kyeong; Nam, Chang-Wook; Hur, Seung-Ho; Kim, Yoon-Nyun; Kim, Kwon-Bae

    2014-01-01

    Arterial stiffness is an important risk factor of impaired left ventricular (LV) diastolic function as well as systolic dysfunction. The cardio-ankle vascular index (CAVI) and the ambulatory arterial stiffness index (AASI) can evaluate arteriosclerosis. We analyzed the relationship between arterial stiffness and diastolic function, and then compared the two methodologies to assess which method could serve as a more informative tool for diastology. In total, 136 patients with hypertension underwent 24-h ambulatory blood pressure monitoring (ABPM) and echocardiography including ventricular arterial coupling (VAC). Arterial stiffness was estimated using both CAVI and AASI derived from ABPM. Patients were classified into LV diastolic dysfunction and normal function groups. Those with diastolic dysfunction had a higher CAVI and AASI. Aside from LV torsion, mitral inflow parameters, tissue Doppler velocities and VAC showed a significantly greater association with CAVI, relative to AASI. The receiver operating characteristic curve analysis revealed that CAVI [area under the curve (AUC) = 0.869, p < 0.001] provided significantly more favorable accuracy for diastolic dysfunction compared with AASI (AUC = 0.672, p = 0.004). Multiple logistic regression analyses showed that CAVI [Odds ratio (OR) = 5.1, p = 0.009] had a greater association with diastolic dysfunction, relative to age, systolic blood pressure or AASI (OR = 1.4, p = 0.043). This study indicates that CAVI clinically provides diastolic functional information much better in hypertensive patients than AASI.

  9. Passive leg movement and nitric oxide-mediated vascular function: the impact of age.

    Science.gov (United States)

    Trinity, Joel D; Groot, H Jonathan; Layec, Gwenael; Rossman, Matthew J; Ives, Stephen J; Morgan, David E; Gmelch, Ben S; Bledsoe, Amber; Richardson, Russell S

    2015-03-15

    In young healthy men, passive leg movement (PLM) elicits a robust nitric oxide (NO)-dependent increase in leg blood flow (LBF), thus providing a novel approach to assess NO-mediated vascular function. While the magnitude of the LBF response to PLM is markedly reduced with age, the role of NO in this attenuated response in the elderly is unknown. Therefore, this study sought to determine the contribution of NO in the PLM-induced LBF with age. Fourteen male subjects (7 young, 24 ± 1 yr; and 7 old, 75 ± 3 yr) underwent PLM with and without NO synthase (NOS) inhibition achieved by intra-arterial infusion of N(G)-monomethyl-L-arginine (L-NMMA). LBF was determined second-by-second by Doppler ultrasound, and central hemodynamics were measured by finger photoplethysmography. NOS inhibition blunted the PLM-induced peak increase in LBF in the young (control: 668 ± 106; 431 ± 95 Δml/min; P = 0.03) but had no effect in the old (control: 266 ± 98; 251 ± 92 Δml/min; P = 0.59). Likewise, the magnitude of the reduction in the overall (i.e., area under the curve) PLM-induced LBF response to NOS inhibition was less in the old (LBF: -31 ± 18 ml) than the young (LBF: -129 ± 21 ml; P PLM-induced LBF in the elderly is primarily due to a reduced contribution to vasodilation from NO and therefore support the use of PLM as a novel approach to assess NO-mediated vascular function across the lifespan.

  10. Coffee polyphenol consumption improves postprandial hyperglycemia associated with impaired vascular endothelial function in healthy male adults.

    Science.gov (United States)

    Jokura, Hiroko; Watanabe, Isamu; Umeda, Mika; Hase, Tadashi; Shimotoyodome, Akira

    2015-10-01

    Epidemiological studies indicate that habitual coffee consumption lowers the risk of diabetes and cardiovascular diseases. Postprandial hyperglycemia is a direct and independent risk factor for cardiovascular diseases. We previously demonstrated that coffee polyphenol ingestion increased secretion of Glucagon-like peptide 1 (GLP-1), which has been shown to exhibit anti-diabetic and cardiovascular effects. We hypothesized coffee polyphenol consumption may improve postprandial hyperglycemia and vascular endothelial function by increasing GLP-1 release and/or reducing oxidative stress. To examine this hypothesis, we conducted a randomized, acute, crossover, intervention study in healthy male adults, measuring blood parameters and flow-mediated dilation (FMD) after ingestion of a meal with or without coffee polyphenol extract (CPE). Nineteen subjects consumed a test meal with either a placebo- or CPE-containing beverage. Blood biomarkers and FMD were measured at fasting and up to 180 minutes postprandially. The CPE beverage led to a significantly lower peak postprandial increase in blood glucose and diacron-reactive oxygen metabolite, and significantly higher postprandial FMD than the placebo beverage. Postprandial blood GLP-1 increase tended to be higher after ingestion of the CPE beverage, compared with placebo. Subclass analysis revealed that the CPE beverage significantly improved postprandial blood GLP-1 response and reduced blood glucose increase in the subjects with a lower insulinogenic index. Correlation analysis showed postprandial FMD was negatively associated with blood glucose increase after ingestion of the CPE beverage. In conclusion, these results suggest that coffee polyphenol consumption improves postprandial hyperglycemia and vascular endothelial function, which is associated with increased GLP-1 secretion and decreased oxidative stress in healthy humans. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Cavitation Resistance in Seedless Vascular Plants: The Structure and Function of Interconduit Pit Membranes.

    Science.gov (United States)

    Brodersen, Craig; Jansen, Steven; Choat, Brendan; Rico, Christopher; Pittermann, Jarmila

    2014-06-01

    Plant water transport occurs through interconnected xylem conduits that are separated by partially digested regions in the cell wall known as pit membranes. These structures have a dual function. Their porous construction facilitates water movement between conduits while limiting the spread of air that may enter the conduits and render them dysfunctional during a drought. Pit membranes have been well studied in woody plants, but very little is known about their function in more ancient lineages such as seedless vascular plants. Here, we examine the relationships between conduit air seeding, pit hydraulic resistance, and pit anatomy in 10 species of ferns (pteridophytes) and two lycophytes. Air seeding pressures ranged from 0.8 ± 0.15 MPa (mean ± sd) in the hydric fern Athyrium filix-femina to 4.9 ± 0.94 MPa in Psilotum nudum, an epiphytic species. Notably, a positive correlation was found between conduit pit area and vulnerability to air seeding, suggesting that the rare-pit hypothesis explains air seeding in early-diverging lineages much as it does in many angiosperms. Pit area resistance was variable but averaged 54.6 MPa s m-1 across all surveyed pteridophytes. End walls contributed 52% to the overall transport resistance, similar to the 56% in angiosperm vessels and 64% in conifer tracheids. Taken together, our data imply that, irrespective of phylogenetic placement, selection acted on transport efficiency in seedless vascular plants and woody plants in equal measure by compensating for shorter conduits in tracheid-bearing plants with more permeable pit membranes. © 2014 American Society of Plant Biologists. All Rights Reserved.

  12. Effects of combined healthy lifestyle factors on functional vascular aging: the Rotterdam Study.

    Science.gov (United States)

    Karimi, Leila; Mattace-Raso, Francesco U S; van Rosmalen, Joost; van Rooij, Frank; Hofman, Albert; Franco, Oscar H

    2016-05-01

    To evaluate whether components of a healthy lifestyle, combined and individually, are associated with arterial stiffness as a marker of functional vascular aging. We included 3235 participants aged 61-96 years from the Rotterdam Study. Measures of arterial stiffness included: aortic pulse wave velocity and carotid distensibility coefficient. Participants were scored one point for each of healthy lifestyle factors: consumption of five or more of fruits and/or vegetables per day, 75 min or more vigorous physical activity per week, 18.5 ≤ BMI ≤ 24. 9, never smoked and light-to-moderate alcohol intake (maximum seven glasses for women and 14 glasses for men) per week. Also a combined score (0-5) was computed by adding the five factors. Linear regression analysis was used to evaluate the association of healthy lifestyle and measures of arterial stiffness adjusting for confounders. Participants had -0.113 [95% confidence interval (CI): -0.196, -0.029] difference in mean aortic pulse wave velocity m/s per unit increment of the lifestyle factors score, independent of cardiovascular risk factors. Higher fruit and vegetable consumption -0.221 (95% CI: -0.409, -0.034) and physical activity -0.239 (95% CI: -0.433, -0.044) were also significantly associated with reduced aortic pulse wave velocity. The corresponding estimates in carotid distensibility coefficient lacked statistical significance when we adjusted for cardiovascular risk factors. Combining multiple healthy lifestyle factors is associated with reduced aortic stiffness, a measure of functional vascular aging and independent of cardiovascular risk factors.

  13. Effects of black raspberry on lipid profiles and vascular endothelial function in patients with metabolic syndrome.

    Science.gov (United States)

    Jeong, Han Saem; Hong, Soon Jun; Lee, Tae-Bum; Kwon, Ji-Wung; Jeong, Jong Tae; Joo, Hyung Joon; Park, Jae Hyoung; Ahn, Chul-Min; Yu, Cheol Woong; Lim, Do-Sun

    2014-10-01

    Black raspberry (Rubus occidentalis) has been known for its anti-inflammatory and anti-oxidant effects. However, short-term effects of black raspberry on lipid profiles and vascular endothelial function have not been investigated in patients with metabolic syndrome. Patients with metabolic syndrome (n = 77) were prospectively randomized into a group with black raspberry (n = 39, 750 mg/day) and a placebo group (n = 38) during a 12-week follow-up. Lipid profiles, brachial artery flow-mediated dilatation (baFMD), and inflammatory cytokines such as IL-6, TNF-α, C-reactive protein, adiponectin, sICAM-1, and sVCAM-1 were measured at the baseline and at the 12-week follow-up. Decreases from the baseline in the total cholesterol level (-22.8 ± 30.4 mg/dL vs. -1.9 ± 31.8 mg/dL, p raspberry than in the placebo group. Increases in baFMD at the 12-week follow-up were significantly greater in the group with black raspberry than in the placebo group (0.33 ± 0.44 mm vs. 0.10 ± 0.35 mm, p raspberry. The use of black raspberry significantly decreased serum total cholesterol level and inflammatory cytokines, thereby improving vascular endothelial function in patients with metabolic syndrome during the 12-week follow-up. Copyright © 2014 John Wiley & Sons, Ltd.

  14. Effects of High-Intensity Intermittent Training on Vascular Function in Obese Preadolescent Boys.

    Science.gov (United States)

    Chuensiri, Napasakorn; Suksom, Daroonwan; Tanaka, Hirofumi

    2018-01-01

    High-intensity intermittent training (HIIT) may serve as an effective alternative to traditional endurance training, since HIIT has been shown to induce greater improvements in aerobic fitness and health-related markers in adult populations. Our objective was to determine whether HIIT and supramaximal high-intensity intermittent training (supra-HIIT) would improve vascular structure and function in obese preadolescent boys. Before the baseline testing, 48 obese preadolescent boys, aged 8-12 years, were randomly assigned into control (CON; n = 16), HIIT (8 × 2 minutes at 90% peak power output, n = 16), and supra-HIIT (8 × 20 seconds at 170% peak power output, n = 16) groups. Both exercise groups performed exercises on a cycle ergometer three times/week for 12 weeks. After 12 weeks, both HIIT and supra-HIIT did not affect body mass, body fat percentage, and waist circumference. Peak oxygen consumption (VO 2 peak) increased in both HIIT and supra-HIIT groups (p < 0.05). Both HIIT and supra-HIIT groups had higher resting metabolic rate than the control group (p < 0.05). A measure of arterial stiffness, brachial-ankle pulse wave velocity, and carotid intima-media thickness decreased after 12 weeks of HIIT and supra-HIIT program (all p < 0.05). Flow-mediated dilation, a measure of endothelium-dependent vasodilation, increased in both HIIT and supra-HIIT groups (all p < 0.05). It is concluded that both HIIT and supra-HIIT have favorable effects on aerobic capacity, metabolic rate, vascular function and structure, and blood lipid profile in obese preadolescent boys. HIIT may be a time efficient and effective exercise for preventing future cardiovascular disease in obese children.

  15. Lung inflammation biomarkers and lung function in children chronically exposed to arsenic

    Energy Technology Data Exchange (ETDEWEB)

    Olivas-Calderón, Edgar, E-mail: edgar_olivascalderon@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); School of Medicine, University Juarez of Durango, Gomez Palacio, Durango (Mexico); Recio-Vega, Rogelio, E-mail: rrecio@yahoo.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Gandolfi, A. Jay, E-mail: gandolfi@pharmacy.arizona.edu [Southwest Environmental Health Science Center, University of Arizona, Tucson, AZ (United States); Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ (United States); Lantz, R. Clark, E-mail: lantz@email.arizona.edu [Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ (United States); Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ (United States); González-Cortes, Tania, E-mail: taniagc2201@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Gonzalez-De Alba, Cesar, E-mail: cesargonzalezalba@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Froines, John R., E-mail: jfroines@ucla.edu [Center for Environmental and Occupational Health, School of Public Health, University of California at Los Angeles, Los Angeles, CA (United States); Espinosa-Fematt, Jorge A., E-mail: dr.jorge.espinosa@gmail.com [School of Medicine, University Juarez of Durango, Gomez Palacio, Durango (Mexico)

    2015-09-01

    Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero has been associated with an increase in respiratory symptoms or diseases in the adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that the exposure to arsenic during early childhood or in utero in children was associated with impairment in the lung function and suggested that this adverse effect could be due to a chronic inflammation response to the metalloid. Therefore, we designed this cross-sectional study in a cohort of children associating lung inflammatory biomarkers and lung function with urinary As levels. A total of 275 healthy children were partitioned into four study groups according with their arsenic urinary levels. Inflammation biomarkers were measured in sputum by ELISA and the lung function was evaluated by spirometry. Fifty eight percent of the studied children were found to have a restrictive spirometric pattern. In the two highest exposed groups, the soluble receptor for advanced glycation end products' (sRAGE) sputum level was significantly lower and matrix metalloproteinase-9 (MMP-9) concentration was higher. When the biomarkers were correlated to the urinary arsenic species, negative associations were found between dimethylarsinic (DMA), monomethylarsonic percentage (%MMA) and dimethylarsinic percentage (%DMA) with sRAGE and positive associations between %DMA with MMP-9 and with the MMP-9/tissue inhibitor of metalloproteinase (TIMP-1) ratio. In conclusion, chronic arsenic exposure of children negatively correlates with sRAGE, and positively correlated with MMP-9 and MMP-9/TIMP-1 levels, and increases the frequency of an abnormal spirometric pattern. Arsenic-induced alterations in inflammatory biomarkers may contribute to the development of restrictive lung diseases. - Highlights: • First study in children evaluating lung inflammatory biomarkers and As levels

  16. Mast cell adenosine receptors function: a focus on the A3 adenosine receptor and inflammation

    Directory of Open Access Journals (Sweden)

    Noam eRudich

    2012-06-01

    Full Text Available Adenosine is a metabolite, which has long been implicated in a variety of inflammatory processes. Inhaled adenosine provokes bronchoconstriction in asthmatics or chronic obstructive pulmonary disease (COPD patients, but not in non-asthmatics. This hyper responsiveness to adenosine appears to be mediated by mast cell activation. These observations have marked the receptor that mediates the bronchoconstrictor effect of adenosine on mast cells, as an attractive drug candidate. Four subtypes (A1, A2a, A2b and A3 of adenosine receptors have been cloned and shown to display distinct tissue distributions and functions. Animal models have firmly established the ultimate role of the A3 adenosine receptor (A3R in mediating hyper responsiveness to adenosine in mast cells, although the influence of the A2b adenosine receptor was confirmed as well. In contrast, studies of the A3R in humans have been controversial. In this review, we summarize data on the role of different adenosine receptors in mast cell regulation of inflammation and pathology, with a focus on the common and distinct functions of the A3R in rodent and human mast cells. The relevance of mouse studies to the human is discussed.

  17. The plant-specific Dof transcription factors family: new players involved in vascular system development and functioning in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Rozenn eLe Hir

    2013-05-01

    Full Text Available In higher plants phloem and xylem are responsible for long-distance transport of water, nutrients, and signals that act systemically at short or long distance to coordinate developmental processes. The formation of the plant vascular system is a complex process that integrates signalling events and gene regulation at transcriptional and posttranscriptional levels. Thanks to transcriptomic and proteomic analysis we start to better understand the mechanisms underlying the formation and the functioning of the vascular system. The role of the DNA-binding with one finger (Dof TFs, a group of plant–specific transcription factors, recently emerged as part of the transcriptional regulatory networks acting on the formation and functioning of the vascular tissues. More than half of the members of this TF family are expressed in the vascular system. In addition some of them have been proposed to be mobile proteins, suggesting a possible role in the control of short- or long-distance signalling as well. This review summarizes the current knowledge on Dof TFs family in Arabidopsis with a special focus on their role in vascular development and functioning.

  18. The plant-specific dof transcription factors family: new players involved in vascular system development and functioning in Arabidopsis.

    Science.gov (United States)

    Le Hir, Rozenn; Bellini, Catherine

    2013-01-01

    In higher plants phloem and xylem are responsible for long-distance transport of water, nutrients, and signals that act systemically at short or long-distance to coordinate developmental processes. The formation of the plant vascular system is a complex process that integrates signaling events and gene regulation at transcriptional and posttranscriptional levels. Thanks to transcriptomic and proteomic analysis we start to better understand the mechanisms underlying the formation and the functioning of the vascular system. The role of the DNA-binding with one finger (Dof TFs), a group of plant-specific transcription factors, recently emerged as part of the transcriptional regulatory networks acting on the formation and functioning of the vascular tissues. More than half of the members of this TF family are expressed in the vascular system. In addition some of them have been proposed to be mobile proteins, suggesting a possible role in the control of short- or long-distance signaling as well. This review summarizes the current knowledge on Dof TFs family in Arabidopsis with a special focus on their role in vascular development and functioning.

  19. Marine n-3 Polyunsaturated Fatty Acids in Psoriatic Arthritis – Inflammation and Cardiac Autonomic and Hemodynamic Function

    DEFF Research Database (Denmark)

    Kristensen, Salome

    This thesis is based on three studies of patients with established psoriatic arthritis (PsA) aiming at investigating the effect of marine n-3 polyunsaturated fatty acids (PUFA) on clinical symptoms and selected measures of inflammation, cardiac autonomic and hemodynamic function in these patients...

  20. Warm ischemia time-dependent variation in liver damage, inflammation, and function in hepatic ischemia/reperfusion injury

    NARCIS (Netherlands)

    Olthof, Pim B.; Golen, van Rowan F.; Meijer, Ben; Beek, van Adriaan A.; Bennink, Roelof J.; Verheij, Joanne; Gulik, van Thomas M.; Heger, Michal

    2017-01-01

    Background Hepatic ischemia/reperfusion (I/R) injury is characterized by hepatocellular damage, sterile inflammation, and compromised postoperative liver function. Generally used mouse I/R models are too severe and poorly reflect the clinical injury profile. The aim was to establish a mouse I/R

  1. Vascular remodelling in asthma.

    Science.gov (United States)

    Walters, Eugene Haydn; Soltani, Amir; Reid, David William; Ward, Chris

    2008-02-01

    We review the recent literature, focusing on 2006 and 2007, to produce an update on the patho-biology of angiogenesis and vascular endothelial growth factor in the asthmatic airway. In terms of conceptual development in asthma research, airway inflammation and remodelling have been regarded as separate processes or perhaps as sequential, with early inflammation leading later to remodelling. Recent insights identify a central role for vascular endothelial growth factor in stimulating both inflammation and vascular remodelling coincidentally, with the full panoply of vascular endothelial growth factor mediated events being complex and wide. Both nitric oxide and matrix metalloproteinase-9 induction may be important downstream pathogenic mechanisms. Virus-mediated exacerbations are a prime manifestation of the oscillating trajectory of clinical asthma. The early stimulation of vascular endothelial growth factor production is probably a central aetiological mechanism, with secondary inflammation and angiogenesis. The time scale of the latter, especially, fits with the time scale of clinico-physiological changes after exacerbation. These vascular endothelial growth factor induced changes are potentially modifiable with therapy. Insights into the importance of vascular endothelial growth factor and angiogenesis in asthma pathogenesis now lead to potential new therapeutic possibilities and elucidate why recent advances in asthma therapeutics have been so successful.

  2. Sex differences in associations of cardio-ankle vascular index with left ventricular function and geometry.

    Science.gov (United States)

    Ye, Zi; Pellikka, Patricia A; Kullo, Iftikhar J

    2017-12-01

    The cardio-ankle vascular index (CAVI) is a measure of global arterial stiffness. We hypothesized that CAVI is associated with left ventricular (LV) function and geometry in individuals without structural heart disease. We measured CAVI in 600 participants (mean age 60.3±14.6 years, 54% men) without history of atherosclerotic cardiovascular disease who were referred for transthoracic echocardiography. Linear regression analysis was used to assess the association of CAVI with LV function (peak mitral annular systolic s' and early diastolic velocity e') and structure (LV mass index (LVMI) and relative wall thickness (RWT)). Older age, male sex, lower body mass index, history of hypertension, diabetes and chronic kidney disease were each associated with a higher CAVI (adjusted R 2 = 0.56, all p 0.1 in men). In conclusion, a higher CAVI, a measure of global arterial stiffness, is associated with worse LV systolic function, worse diastolic relaxation, and greater LV RWT in both men and women, and with LVMI in women.

  3. Important Roles of Ring Finger Protein 112 in Embryonic Vascular Development and Brain Functions.

    Science.gov (United States)

    Tsou, Jen-Hui; Yang, Ying-Chen; Pao, Ping-Chieh; Lin, Hui-Ching; Huang, Nai-Kuei; Lin, Shih-Ting; Hsu, Kuei-Sen; Yeh, Che-Ming; Lee, Kuen-Haur; Kuo, Chu-Jen; Yang, De-Ming; Lin, Jiann-Her; Chang, Wen-Chang; Lee, Yi-Chao

    2017-04-01

    Rnf112 is a member of the RING finger protein family. The expression of Rnf112 is abundant in the brain and is regulated during brain development. Our previous study has revealed that Rnf112 can promote neuronal differentiation by inhibiting the progression of the cell cycle in cell models. In this study, we further revealed the important functions of Rnf112 in embryo development and in adult brain. Our data showed that most of the Rnf112 -/- embryos exhibited blood vascular defects and died in utero. Upon further investigation, we found that the survival rate of homozygous Rnf112 knockout mice in 129/sv and C57BL/6 mixed genetic background was increased. The survived newborns of Rnf112 -/- mice manifested growth retardation as indicated by smaller size and a reduced weight. Although the overall organization of the brain did not appear to be severely affected in Rnf112 -/- mice, using in vivo 3D MRI imaging, we found that when compared to wild-type littermates, brains of Rnf112 -/- mice were smaller. In addition, Rnf112 -/- mice displayed impairment of brain functions including motor balance, and spatial learning and memory. Our results provide important aspects for the study of Rnf112 gene functions.

  4. Silk biomaterials functionalized with recombinant domain V of human perlecan modulate endothelial cell and platelet interactions for vascular applications.

    Science.gov (United States)

    Rnjak-Kovacina, Jelena; Tang, Fengying; Whitelock, John M; Lord, Megan S

    2016-12-01

    Modulation of endothelial cell and platelet interactions is an essential feature of vascular materials. Silk biomaterials were functionalized with recombinantly expressed domain V of human perlecan, an essential vascular proteoglycan involved in vasculogenesis, angiogenesis and wound healing, using passive adsorption or covalent cross-linking via carbodiimide chemistry. The orientation of domain V on the surface of silk biomaterials was modulated by the immobilization technique and glycosaminoglycan chains played an essential role in the proteoglycan presentation on the material surface. Covalent immobilization supported improved integrin binding site presentation to endothelial cells compared to passive adsorption in the presence of glycosaminoglycan chains, but removal of glycosaminoglycan chains resulted in reduced integrin site availability and thus cell binding. Silk biomaterials covalently functionalized with domain V supported endothelial cell adhesion, spreading and proliferation and were anti-adhesive for platelets, making them promising surfaces for the development of the next-generation vascular grafts. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Acute Impact of Tobacco vs Electronic Cigarette Smoking on Oxidative Stress and Vascular Function.

    Science.gov (United States)

    Carnevale, Roberto; Sciarretta, Sebastiano; Violi, Francesco; Nocella, Cristina; Loffredo, Lorenzo; Perri, Ludovica; Peruzzi, Mariangela; Marullo, Antonino G M; De Falco, Elena; Chimenti, Isotta; Valenti, Valentina; Biondi-Zoccai, Giuseppe; Frati, Giacomo

    2016-09-01

    The vascular safety of electronic cigarettes (e-Cigarettes) must still be clarified. We compared the impact of e-Cigarettes vs traditional tobacco cigarettes on oxidative stress and endothelial function in healthy smokers and nonsmoker adults. A crossover, single-blind study was performed in 40 healthy subjects (20 smokers and 20 nonsmokers, matched for age and sex). First, all subjects smoked traditional tobacco cigarettes. One week later, the same subjects smoked an e-Cigarette with the same nominal nicotine content. Blood samples were drawn just before and after smoking, and markers of oxidative stress, nitric oxide bioavailability, and vitamin E levels were measured. Flow-mediated dilation (FMD) was also measured. Smoking both e-Cigarettes and traditional cigarettes led to a significant increase in the levels of soluble NOX2-derived peptide and 8-iso-prostaglandin F2α and a significant decrease in nitric oxide bioavailability, vitamin E levels, and FMD. Generalized estimating equation analysis confirmed that all markers of oxidative stress and FMD were significantly affected by smoking and showed that the biologic effects of e-Cigarettes vstraditional cigarettes on vitamin E levels (P = .413) and FMD (P = .311) were not statistically different. However, e-Cigarettes seemed to have a lesser impact than traditional cigarettes on levels of soluble NOX2-derived peptide (P = .001), 8-iso-prostaglandin F2α (P = .046), and nitric oxide bioavailability (P = .001). Our study showed that both cigarettes have unfavorable effects on markers of oxidative stress and FMD after single use, although e-Cigarettes seemed to have a lesser impact. Future studies are warranted to clarify the chronic vascular effects of e-Cigarette smoking. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  6. Functional implication of Dp71 in osmoregulation and vascular permeability of the retina.

    Directory of Open Access Journals (Sweden)

    Abdoulaye Sene

    Full Text Available Functional alterations of Müller cells, the principal glia of the retina, are an early hallmark of most retina diseases and contribute to their further progression. The molecular mechanisms of these reactive Müller cell alterations, resulting in disturbed retinal homeostasis, remain largely unknown. Here we show that experimental detachment of mouse retina induces mislocation of the inwardly rectifying potassium channels (Kir4.1 and a downregulation of the water channel protein (AQP4 in Müller cells. These alterations are associated with a strong decrease of Dp71, a cytoskeleton protein responsible for the localization and the clustering of Kir4.1 and AQP4. Partial (in detached retinas or total depletion of Dp71 in Müller cells (in Dp71-null mice impairs the capability of volume regulation of Müller cells under osmotic stress. The abnormal swelling of Müller cells In Dp71-null mice involves the action of inflammatory mediators. Moreover, we investigated whether the alterations in Müller cells of Dp71-null mice may interfere with their regulatory effect on the blood-retina barrier. In the absence of Dp71, the retinal vascular permeability was increased as compared to the controls. Our results reveal that Dp71 is crucially implicated in the maintenance of potassium homeostasis, in transmembraneous water transport, and in the Müller cell-mediated regulation of retinal vascular permeability. Furthermore, our data provide novel insights into the mechanisms of retinal homeostasis provided by Müller cells under normal and pathological conditions.

  7. Impaired Coronary and Renal Vascular Function in Spontaneously Type 2 Diabetic Leptin-Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Helena U Westergren

    Full Text Available Type 2 diabetes is associated with macro- and microvascular complications in man. Microvascular dysfunction affects both cardiac and renal function and is now recognized as a main driver of cardiovascular mortality and morbidity. However, progression of microvascular dysfunction in experimental models is often obscured by macrovascular pathology and consequently demanding to study. The obese type 2 diabetic leptin-deficient (ob/ob mouse lacks macrovascular complications, i.e. occlusive atherosclerotic disease, and may therefore be a potential model for microvascular dysfunction. The present study aimed to test the hypothesis that these mice with an insulin resistant phenotype might display microvascular dysfunction in both coronary and renal vascular beds.In this study we used non-invasive Doppler ultrasound imaging to characterize microvascular dysfunction during the progression of diabetes in ob/ob mice. Impaired coronary flow velocity reserve was observed in the ob/ob mice at 16 and 21 weeks of age compared to lean controls. In addition, renal resistivity index as well as pulsatility index was higher in the ob/ob mice at 21 weeks compared to lean controls. Moreover, plasma L-arginine was lower in ob/ob mice, while asymmetric dimethylarginine was unaltered. Furthermore, a decrease in renal vascular density was observed in the ob/ob mice.In parallel to previously described metabolic disturbances, the leptin-deficient ob/ob mice also display cardiac and renal microvascular dysfunction. This model may therefore be suitable for translational, mechanistic and interventional studies to improve the understanding of microvascular complications in type 2 diabetes.

  8. Amiloride Improves Endothelial Function and Reduces Vascular Stiffness in Female Mice Fed a Western Diet

    Directory of Open Access Journals (Sweden)

    Luis A. Martinez-Lemus

    2017-06-01

    Full Text Available Obese premenopausal women lose their sex related cardiovascular disease protection and develop greater arterial stiffening than age matched men. In female mice, we have shown that consumption of a Western diet (WD, high in fat and refined sugars, is associated with endothelial dysfunction and vascular stiffening, which occur via activation of mineralocorticoid receptors and associated increases in epithelial Na+ channel (ENaC activity on endothelial cells (EnNaC. Herein our aim was to determine the effect that reducing EnNaC activity with a very-low-dose of amiloride would have on decreasing endothelial and arterial stiffness in young female mice consuming a WD. To this end, we fed female mice either a WD or control diet and treated them with or without a very-low-dose of the ENaC-inhibitor amiloride (1 mg/kg/day in the drinking water for 20 weeks beginning at 4 weeks of age. Mice consuming a WD were heavier and had greater percent body fat, proteinuria, and aortic stiffness as assessed by pulse-wave velocity than those fed control diet. Treatment with amiloride did not affect body weight, body composition, blood pressure, urinary sodium excretion, or insulin sensitivity, but significantly reduced the development of endothelial and aortic stiffness, aortic fibrosis, aortic oxidative stress, and mesenteric resistance artery EnNaC abundance and proteinuria in WD-fed mice. Amiloride also improved endothelial-dependent vasodilatory responses in the resistance arteries of WD-fed mice. These results indicate that a very-low-dose of amiloride, not affecting blood pressure, is sufficient to improve endothelial function and reduce aortic stiffness in female mice fed a WD, and suggest that EnNaC-inhibition may be sufficient to ameliorate the pathological vascular stiffening effects of WD-induced obesity in females.

  9. Endothelial mechanotransduction proteins and vascular function are altered by dietary sucrose supplementation in healthy young male subjects.

    Science.gov (United States)

    Gliemann, Lasse; Rytter, Nicolai; Lindskrog, Mads; Slingsby, Martina H Lundberg; Åkerström, Thorbjörn; Sylow, Lykke; Richter, Erik A; Hellsten, Ylva

    2017-08-15

    Mechanotransduction in endothelial cells is a central mechanism in the regulation of vascular tone and vascular remodelling Mechanotransduction and vascular function may be affected by high sugar levels in plasma because of a resulting increase in oxidative stress and increased levels of advanced glycation end-products (AGE). In healthy young subjects, 2 weeks of daily supplementation with 3 × 75 g of sucrose was found to reduce blood flow in response to passive lower leg movement and in response to 12 W of knee extensor exercise. This vascular impairment was paralleled by up-regulation of platelet endothelial cell adhesion molecule (PECAM)-1, endothelial nitric oxide synthase, NADPH oxidase and Rho family GTPase Rac1 protein expression, an increased basal phosphorylation status of vascular endothelial growth factor receptor 2 and a reduced phosphorylation status of PECAM-1. There were no measurable changes in AGE levels. The findings of the present study demonstrate that daily high sucrose intake markedly affects mechanotransduction proteins and has a detrimental effect on vascular function. Endothelial mechanotransduction is important for vascular function but alterations and activation of vascular mechanosensory proteins have not been investigated in humans. In endothelial cell culture, simple sugars effectively impair mechanosensor proteins. To study mechanosensor- and vascular function in humans, 12 young healthy male subjects supplemented their diet with 3 × 75 g sucrose day(-1) for 14 days in a randomized cross-over design. Before and after the intervention period, the hyperaemic response to passive lower leg movement and active knee extensor exercise was determined by ultrasound doppler. A muscle biopsy was obtained from the thigh muscle before and after acute passive leg movement to allow assessment of protein amounts and the phosphorylation status of mechanosensory proteins and NADPH oxidase. The sucrose intervention led to a reduced flow

  10. Grip strength in mice with joint inflammation: A rheumatology function test sensitive to pain and analgesia.

    Science.gov (United States)

    Montilla-García, Ángeles; Tejada, Miguel Á; Perazzoli, Gloria; Entrena, José M; Portillo-Salido, Enrique; Fernández-Segura, Eduardo; Cañizares, Francisco J; Cobos, Enrique J

    2017-10-01

    Grip strength deficit is a measure of pain-induced functional disability in rheumatic disease. We tested whether this parameter and tactile allodynia, the standard pain measure in preclinical studies, show parallels in their response to analgesics and basic mechanisms. Mice with periarticular injections of complete Freund's adjuvant (CFA) in the ankles showed periarticular immune infiltration and synovial membrane alterations, together with pronounced grip strength deficits and tactile allodynia measured with von Frey hairs. However, inflammation-induced tactile allodynia lasted longer than grip strength alterations, and therefore did not drive the functional deficits. Oral administration of the opioid drugs oxycodone (1-8 mg/kg) and tramadol (10-80 mg/kg) induced a better recovery of grip strength than acetaminophen (40-320 mg/kg) or the nonsteroidal antiinflammatory drugs ibuprofen (10-80 mg/kg) or celecoxib (40-160 mg/kg); these results are consistent with their analgesic efficacy in humans. Functional impairment was generally a more sensitive indicator of drug-induced analgesia than tactile allodynia, as drug doses that attenuated grip strength deficits showed little or no effect on von Frey thresholds. Finally, ruthenium red (a nonselective TRP antagonist) or the in vivo ablation of TRPV1-expressing neurons with resiniferatoxin abolished tactile allodynia without altering grip strength deficits, indicating that the neurobiology of tactile allodynia and grip strength deficits differ. In conclusion, grip strength deficits are due to a distinct type of pain that reflects an important aspect of the human pain experience, and therefore merits further exploration in preclinical studies to improve the translation of new analgesics from bench to bedside. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Balanced Hydroxyethylstarch (HES 130/0.4 Impairs Kidney Function In-Vivo without Inflammation.

    Directory of Open Access Journals (Sweden)

    Martin Alexander Schick

    Full Text Available Volume therapy is a standard procedure in daily perioperative care, and there is an ongoing discussion about the benefits of colloid resuscitation with hydroxyethylstarch (HES. In sepsis HES should be avoided due to a higher risk for acute kidney injury (AKI. Results of the usage of HES in patients without sepsis are controversial. Therefore we conducted an animal study to evaluate the impact of 6% HES 130/0.4 on kidney integrity with sepsis or under healthy conditions Sepsis was induced by standardized Colon Ascendens Stent Peritonitis (sCASP. sCASP-group as well as control group (C remained untreated for 24 h. After 18 h sCASP+HES group (sCASP+VOL and control+HES (C+VOL received 50 ml/KG balanced 6% HES (VOL 130/0.4 over 6 h. After 24 h kidney function was measured via Inulin- and PAH-Clearance in re-anesthetized rats, and serum urea, creatinine (crea, cystatin C and Neutrophil gelatinase-associated lipocalin (NGAL as well as histopathology were analysed. In vitro human proximal tubule cells (PTC were cultured +/- lipopolysaccharid (LPS and with 0.1-4.0% VOL. Cell viability was measured with XTT-, cell toxicity with LDH-test. sCASP induced severe septic AKI demonstrated divergent results regarding renal function by clearance or creatinine measure focusing on VOL. Soleley HES (C+VOL deteriorated renal function without sCASP. Histopathology revealed significantly derangements in all HES groups compared to control. In vitro LPS did not worsen the HES induced reduction of cell viability in PTC cells. For the first time, we demonstrated, that application of 50 ml/KG 6% HES 130/0.4 over 6 hours induced AKI without inflammation in vivo. Severity of sCASP induced septic AKI might be no longer susceptible to the way of volume expansion.

  12. Smooth Muscle-Targeted Overexpression of Peroxisome Proliferator Activated Receptor-γ Disrupts Vascular Wall Structure and Function.

    Directory of Open Access Journals (Sweden)

    Jennifer M Kleinhenz

    Full Text Available Activation of the nuclear hormone receptor, PPARγ, with pharmacological agonists promotes a contractile vascular smooth muscle cell phenotype and reduces oxidative stress and cell proliferation, particularly under pathological conditions including vascular injury, restenosis, and atherosclerosis. However, pharmacological agonists activate both PPARγ-dependent and -independent mechanisms in multiple cell types confounding efforts to clarify the precise role of PPARγ in smooth muscle cell structure and function in vivo. We, therefore, designed and characterized a mouse model with smooth muscle cell-targeted PPARγ overexpression (smPPARγOE. Our results demonstrate that smPPARγOE attenuated contractile responses in aortic rings, increased aortic compliance, caused aortic dilatation, and reduced mean arterial pressure. Molecular characterization revealed that compared to littermate control mice, aortas from smPPARγOE mice expressed lower levels of contractile proteins and increased levels of adipocyte-specific transcripts. Morphological analysis demonstrated increased lipid deposition in the vascular media and in smooth muscle of extravascular tissues. In vitro adenoviral-mediated PPARγ overexpression in human aortic smooth muscle cells similarly increased adipocyte markers and lipid uptake. The findings demonstrate that smooth muscle PPARγ overexpression disrupts vascular wall structure and function, emphasizing that balanced PPARγ activity is essential for vascular smooth muscle homeostasis.

  13. Exercise training improves vascular function in adolescents with type 2 diabetes.

    Science.gov (United States)

    Naylor, Louise H; Davis, Elizabeth A; Kalic, Rachelle J; Paramalingam, Niru; Abraham, Mary B; Jones, Timothy W; Green, Daniel J

    2016-02-01

    The impact of exercise training on vascular health in adolescents with type 2 diabetes has not been previously studied. We hypothesized that exercise training would improve micro- and macrovascular health in adolescents with type 2 diabetes. Thirteen adolescents (13-21 years, 10F) with type 2 diabetes were recruited from Princess Margaret Hospital. Participants were randomized to receive either an exercise program along with standard clinical care (n = 8) or standard care alone (n = 5). Those in the intervention group received 12 weeks of gym-based, personalized, and supervised exercise training. Those in the control group were instructed to maintain usual activity levels. Assessments were conducted at baseline and following week 12. The exercise group was also studied 12 weeks following the conclusion of their program. Assessments consisted of conduit artery endothelial function (flow-mediated dilation, FMD) and microvascular function (cutaneous laser Doppler). Secondary outcomes included body composition (dual-energy X-ray absorptiometry, DXA), glycemic control (whole body insulin sensitivity, M) assessed using the euglycemic-hyperinsulinemic clamp protocol, cardiorespiratory fitness (V˙O2peak), and muscular strength (1RM). Exercise training increased FMD (P function (P function were reversed. This study indicates that exercise training can improve both conduit and microvascular endothelial function and health, independent of changes in insulin sensitivity in adolescents with type 2 diabetes. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  14. The anti-inflammatory function of HDL is impaired in type 2 diabetes: role of hyperglycemia, paraoxonase-1 and low grade inflammation.

    Science.gov (United States)

    Ebtehaj, Sanam; Gruppen, Eke G; Parvizi, Mojtaba; Tietge, Uwe J F; Dullaart, Robin P F

    2017-10-12

    Functional properties of high density lipoproteins (HDL) are increasingly recognized to play a physiological role in atheroprotection. Type 2 diabetes mellitus (T2DM) is characterized by low HDL cholesterol, but the effect of chronic hyperglycemia on the anti-inflammatory capacity of HDL, a metric of HDL function, is unclear. Therefore, the aim of the present study was to establish the impact of T2DM on the HDL anti-inflammatory capacity, taking paraoxonase-1 (PON-1) activity and low grade inflammation into account. The HDL anti-inflammatory capacity, determined as the ability to suppress tumor necrosis factor-α (TNF-α) induced vascular cell adhesion molecule-1 (VCAM-1) mRNA expression in endothelial cells in vitro (higher values indicate lower anti-inflammatory capacity), PON-1 (arylesterase) activity, hs-C-reactive protein (hs-CRP), serum amyloid A (SAA) and TNF-α were compared in 40 subjects with T2DM (no insulin or statin treatment) and 36 non-diabetic subjects. T2DM was associated with impaired HDL anti-inflammatory capacity (3.18 vs 1.05 fold increase in VCAM-1 mRNA expression; P 23), as well as increased hs-CRP (P = 0.043) and TNF-α (P = 0.005). In all subjects combined, age- and sex-adjusted multivariable linear regression analysis demonstrated that impaired HDL anti-inflammatory capacity was associated with hyperglycemia (β = 0.499, P 2, P = 0.030) and higher hs-CRP (β = 0.220, P = 0.016). The HDL anti-inflammatory capacity is substantially impaired in T2DM, at least partly attributable to the degree of hyperglycemia, decreased PON-1 activity and enhanced low grade chronic inflammation. Decreased anti-inflammatory protection capacity of HDL conceivably contributes to the increased atherosclerosis risk associated with T2DM.

  15. Characterization of the in vitro binding and inhibition kinetics of primary amine oxidase/vascular adhesion protein-1 by glucosamine.

    LENUS (Irish Health Repository)

    Olivieri, Aldo

    2012-04-01

    Primary-amine oxidase (PrAO) catalyzes the oxidative deamination of endogenous and exogenous primary amines and also functions, in some tissues, as an inflammation-inducible endothelial factor, known as vascular adhesion protein-1. VAP-1 mediates the slow rolling and adhesion of lymphocytes to endothelial cells in a number of inflammatory conditions, including inflammation of the synovium.

  16. Exercise protects from cancer through regulation of immune function and inflammation.

    Science.gov (United States)

    Hojman, Pernille

    2017-08-15

    Exercise training has been extensively studied in cancer settings as part of prevention or rehabilitation strategies, yet emerging evidence suggests that exercise training can also directly affect tumor-specific outcomes. The underlying mechanisms for this exercise-dependent cancer protection are just starting to be elucidated. To this end, evasion of immune surveillance and tumor-associated inflammation are established as hallmarks of cancer, and exercise may target cancer incidence and progression through regulation of these mechanisms. Here, I review the role of exercise in protection from cancer through mobilization and activation of cytotoxic immune cells, restriction of inflammatory signaling pathways in myeloid immune cells, and regulation of acute and chronic systemic inflammatory responses. In conclusion, I propose that exercise has the potential to target tumor growth through regulation of immune and inflammatory functions, and exercise may be pursued as anticancer treatment through incorporation into standard oncological therapy to the benefit of the cancer patients. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  17. Persisting Inflammation and Chronic Immune Activation but Intact Cognitive Function in HIV-Infected Patients After Long-Term Treatment With Combination Antiretroviral Therapy

    DEFF Research Database (Denmark)

    Pedersen, Karin K; Pedersen, Maria; Gaardbo, Julie C

    2013-01-01

    Impaired cognitive function in HIV-infected patients has been suggested. Treatment with combination antiretroviral therapy (cART) restores CD4⁺ cell counts and suppresses viral replication, but immune activation and inflammation may persist. The aim of the study was to examine if cognitive function...... in HIV-infected patients was related to immune activation and inflammation....

  18. Vascular functioning and the water balance of ripening kiwifruit (Actinidia chinensis) berries.

    Science.gov (United States)

    Clearwater, Michael J; Luo, Zhiwei; Ong, Sam Eng Chye; Blattmann, Peter; Thorp, T Grant

    2012-03-01

    Indirect evidence suggests that water supply to fleshy fruits during the final stages of development occurs through the phloem, with the xylem providing little water, or acting as a pathway for water loss back to the plant. This inference was tested by examining the water balance and vascular functioning of ripening kiwifruit berries (Actinidia chinensis var. chinensis 'Hort16A') exhibiting a pre-harvest 'shrivel' disorder in California, and normal development in New Zealand. Dye labelling and mass balance experiments indicated that the xylem and phloem were both functional and contributed approximately equally to the fruit water supply during this stage of development. The modelled fruit water balance was dominated by transpiration, with net water loss under high vapour pressure deficit (D(a)) conditions in California, but a net gain under cooler New Zealand conditions. Direct measurement of pedicel sap flow under controlled conditions confirmed inward flows in both the phloem and xylem under conditions of both low and high D(a). Phloem flows were required for growth, with gradual recovery after a step increase in D(a). Xylem flows alone were unable to support growth, but did supply transpiration and were responsive to D(a)-induced pressure fluctuations. The results suggest that the shrivel disorder was a consequence of a high fruit transpiration rate, and that the perception of complete loss or reversal of inward xylem flows in ripening fruits should be re-examined.

  19. Effect of apple polyphenols on vascular oxidative stress and endothelium function: a translational study.

    Science.gov (United States)

    Cicero, Arrigo F G; Caliceti, Cristiana; Fogacci, Federica; Giovannini, Marina; Calabria, Donato; Colletti, Alessandro; Veronesi, Maddalena; Roda, Aldo; Borghi, Claudio

    2017-07-29

    We aimed examining apple polyphenols' effect on uricemia and endothelial function in a sample of overweight subjects. This was a two-phased study. In vitro experiment aimed to evaluate apple polyphenols' ability to lower uric acid in comparison with allopurinol. In vivo study consisted in a randomized, double-blind, parallel placebo-controlled clinical trial involving 62 overweight volunteers with suboptimal values of fasting plasma glucose (100 mg/dL≤FPG≤125 mg/dL), randomized to 300 mg apple polyphenols or placebo for 8 weeks. Apple polyphenols extract inhibited xanthine oxidase activity, with an IC50 = 130 ± 30 ng/mL; reducing uric acid production with an IC50 = 154 ± 28 ng/mL. During the trial, after the first 4 weeks of treatment, FPG decreased in the active treated group (-6.1%, p apple polyphenols extract has a positive effect on vascular oxidative stress and endothelium function and reduce FPG and uric acid by inhibiting xanthine oxidase, as our In vitro experiment attests. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Localization and function of KLF4 in cytoplasm of vascular smooth muscle cell

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yan [Department of Biochemistry and Molecular Biology, The Key Laboratory of Neurobiology and Vascular Biology (China); The Third Hospital of Hebei Medical University, Shijazhuang (China); Zheng, Bin; Zhang, Xin-hua; Nie, Chan-juan; Li, Yong-hui [Department of Biochemistry and Molecular Biology, The Key Laboratory of Neurobiology and Vascular Biology (China); Wen, Jin-kun, E-mail: wjk@hebmu.edu.cn [Department of Biochemistry and Molecular Biology, The Key Laboratory of Neurobiology and Vascular Biology (China)

    2013-06-28

    Highlights: •PDGF-BB prompts the translocation of KLF4 to the cytoplasm. •PDGF-BB promotes interaction between KLF4 and actin in the cytoplasm. •Phosphorylation and SUMOylation of KLF4 participates in regulation of cytoskeletal organization. •KLF4 regulates cytoskeleton by promoting the expression of contraction-associated genes. -- Abstract: The Krüppel-like factor 4 is a DNA-binding transcriptional regulator that regulates a diverse array of cellular processes, including development, differentiation, proliferation, and apoptosis. The previous studies about KLF4 functions mainly focused on its role as a transcription factor, its functions in the cytoplasm are still unknown. In this study, we found that PDGF-BB could prompt the translocation of KLF4 to the cytoplasm through CRM1-mediated nuclear export pathway in vascular smooth muscle cells (VSMCs) and increased the interaction of KLF4 with actin in the cytoplasm. Further study showed that both KLF4 phosphorylation and SUMOylation induced by PDGF-BB participates in regulation of cytoskeletal organization by stabilizing the actin cytoskeleton in VSMCs. In conclusion, these results identify that KLF4 participates in the cytoskeletal organization by stabilizing cytoskeleton in the cytoplasm of VSMCs.

  1. Role of folic acid in nitric oxide bioavailability and vascular endothelial function.

    Science.gov (United States)

    Stanhewicz, Anna E; Kenney, W Larry

    2017-01-01

    Folic acid is a member of the B-vitamin family and is essential for amino acid metabolism. Adequate intake of folic acid is vital for metabolism, cellular homeostasis, and DNA synthesis. Since the initial discovery of folic acid in the 1940s, folate deficiency has been implicated in numerous disease states, primarily those associated with neural tube defects in utero and neurological degeneration later in life. However, in the past decade, epidemiological studies have identified an inverse relation between both folic acid intake and blood folate concentration and cardiovascular health. This association inspired a number of clinical studies that suggested that folic acid supplementation could reverse endothelial dysfunction in patients with cardiovascular disease (CVD). Recently, in vitro and in vivo studies have begun to elucidate the mechanism(s) through which folic acid improves vascular endothelial function. These studies, which are the focus of this review, suggest that folic acid and its active metabolite 5-methyl tetrahydrofolate improve nitric oxide (NO) bioavailability by increasing endothelial NO synthase coupling and NO production as well as by directly scavenging superoxide radicals. By improving NO bioavailability, folic acid may protect or improve endothelial function, thereby preventing or reversing the progression of CVD in those with overt disease or elevated CVD risk. © The Author(s) 2016. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Systemic vascular function, measured with forearm flow mediated dilatation, in acute and stable cerebrovascular disease: a case-control study

    Directory of Open Access Journals (Sweden)

    Blacker David

    2010-10-01

    Full Text Available Abstract Background Acute ischaemic stroke is associated with alteration in systemic markers of vascular function. We measured forearm vascular function (using forearm flow mediated dilatation to clarify whether recent acute ischaemic stroke/TIA is associated with impaired systemic vascular function. Methods Prospective case control study enrolling 17 patients with recent acute ischaemic stroke/TIA and 17 sex matched controls with stroke more than two years previously. Forearm vascular function was measured using flow medicated dilatation (FMD. Results Flow mediated dilatation was 6.0 ± 1.1% in acute stroke/TIA patients and 4.7 ± 1.0% among control subjects (p = 0.18. The mean paired difference in FMD between subjects with recent acute stroke and controls was 1.25% (95% CI -0.65, 3.14; p = 0.18. Endothelium independent dilatation was measured in six pairs of participants and was similar in acute stroke/TIA patients (22.6 ± 4.3% and control subjects (19.1 ± 2.6%; p = 0.43. Conclusions Despite the small size of this study, these data indicate that recent acute stroke is not necessarily associated with a clinically important reduction in FMD.

  3. Effect of intermittent vitamin D3 on vascular function and symptoms in chronic fatigue syndrome--a randomised controlled trial.

    Science.gov (United States)

    Witham, M D; Adams, F; McSwiggan, S; Kennedy, G; Kabir, G; Belch, J J F; Khan, F

    2015-03-01

    Low 25-hydroxyvitamin D levels are common in patients with chronic fatigue syndrome; such patients also manifest impaired vascular health. We tested whether high-dose intermittent oral vitamin D therapy improved markers of vascular health and fatigue in patients with chronic fatigue syndrome. Parallel-group, double-blind, randomised placebo-controlled trial. Patients with chronic fatigue syndrome according to the Fukuda (1994) and Canadian (2003) criteria were randomised to receive 100,000 units oral vitamin D3 or matching placebo every 2 months for 6 months. The primary outcome was arterial stiffness measured using carotid-femoral pulse wave velocity at 6 months. Secondary outcomes included flow-mediated dilatation of the brachial artery, blood pressure, cholesterol, insulin resistance, markers of inflammation and oxidative stress, and the Piper Fatigue scale. As many as 50 participants were randomised; mean age 49 (SD 13) years, mean baseline pulse wave velocity 7.8 m/s (SD 2.3), mean baseline office blood pressure 128/78 (18/12) mmHg and mean baseline 25-hydroxyvitamin D level 46 (18) nmol/L. 25-hydroxyvitamin D levels increased by 22 nmol/L at 6 months in the treatment group relative to placebo. There was no effect of treatment on pulse wave velocity at 6 months (adjusted treatment effect 0.0 m/s; 95% CI -0.6 to 0.6; p = 0.93). No improvement was seen in other vascular and metabolic outcomes, or in the Piper Fatigue scale at 6 months (adjusted treatment effect 0.2 points; 95% CI -0.8 to 1.2; p = 0.73). High-dose oral vitamin D3 did not improve markers of vascular health or fatigue in patients with chronic fatigue syndrome. www.controlled-trials.com, ISRCTN59927814. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Exposure to ambient concentrations of particulate air pollution does not influence vascular function or inflammatory pathways in young healthy individuals

    DEFF Research Database (Denmark)

    Bräuner, E. V.; Møller, P.; Barregård, L.

    2008-01-01

    Background: Particulate air pollution is associated with increased risk of cardiovascular events although the involved mechanisms are poorly understood. The objective of the present study was to investigate the effects of controlled exposure to ambient air fine and ultrafine particles on microvas...... with detectable systemic inflammation, lipid or protein oxidation, altered haemostasis or microvascular function in young healthy participants....

  5. Integrin-specific hydrogels functionalized with VEGF for vascularization and bone regeneration of critical-size bone defects

    Science.gov (United States)

    García, José R.; Clark, Amy Y.; García, Andrés J.

    2016-01-01

    Vascularization of bone defects is considered a crucial component to the successful regeneration of large bone defects. Although vascular endothelial growth factor (VEGF) has been delivered to critical-size bone defect models to augment blood vessel infiltration into the defect area, its potential to increase bone repair remains ambiguous. In this study, we investigated whether integrin-specific biomaterials modulate the effects of VEGF on bone regeneration. We engineered protease-degradable, VEGF-loaded polyethylene glycol (PEG) hydrogels functionalized with either a triple-helical, α2β1 integrin-specific peptide (GFOGER) or an αvβ3 integrin-targeting peptide (RGD). Covalent incorporation of VEGF into the PEG hydrogel allowed for protease degradation-dependent release of the protein while maintaining VEGF bioactivity. When applied to critical-size segmental defects in the murine radius, GFOGER-functionalized VEGF-free hydrogels exhibited significantly increased vascular volume and density and resulted in a larger number of thicker blood vessels compared to RGD-functionalized VEGF-free hydrogels. VEGF-loaded RGD hydrogels increased vascularization compared to VEGF-free RGD hydrogels, but the levels of vascularization for these VEGF-containing RGD hydrogels were similar to those of VEGF-free GFOGER hydrogels. VEGF transiently increased bone regeneration in RGD hydrogels but had no effect at later time points. In GFOGER hydrogels, VEGF did not show an effect on bone regeneration. However, VEGF-free GFOGER hydrogels resulted in increased bone regeneration compared to VEGF-free RGD hydrogels. These findings demonstrate the importance of integrin-specificity in engineering constructs for vascularization and associated bone regeneration. PMID:26662727

  6. Adipose stromal vascular fraction cell construct sustains coronary microvascular function after acute myocardial infarction

    Science.gov (United States)

    LeBlanc, Amanda J.; Touroo, Jeremy S.; Hoying, James B.

    2012-01-01

    A three-dimensional tissue construct was created using adipose-derived stromal vascular fraction (SVF) cells and evaluated as a microvascular protection treatment in a myocardial infarction (MI) model. This study evaluated coronary blood flow (BF) and global left ventricular function after MI with and without the SVF construct. Fischer-344 rats were separated into four groups: sham operation (sham), MI, MI Vicryl patch (no cells), and MI SVF construct (MI SVF). SVF cells were labeled with green fluorescent protein (GFP). Immediately postinfarct, constructs were implanted onto the epicardium at the site of ischemia. Four weeks postsurgery, the coronary BF reserve was significantly decreased by 67% in the MI group and 75% in the MI Vicryl group compared with the sham group. The coronary BF reserve of the sham and MI SVF groups in the area at risk was not significantly different (sham group: 83 ± 22% and MI SVF group: 57 ± 22%). Griffonia simplicifolia I and GFP-positive SVF immunostaining revealed engrafted SVF cells around microvessels in the infarct region 4 wk postimplant. Overall heart function, specifically ejection fraction, was significantly greater in MI SVF hearts compared with MI and MI Vicryl hearts (MI SVF: 66 ± 4%, MI: 37 ± 8%, and MI Vicryl: 29 ± 6%). In conclusion, adipose-derived SVF cells can be used to construct a novel therapeutic modality for treating microvascular instability and ischemia through implantation on the epicardial surface of the heart. The SVF construct implanted immediately after MI not only maintains heart function but also sustains microvascular perfusion and function in the infarct area by sustaining the coronary BF reserve. PMID:22140045

  7. Air Pollution, Airway Inflammation, and Lung Function in a Cohort Study of Mexico City Schoolchildren

    Science.gov (United States)

    Barraza-Villarreal, Albino; Sunyer, Jordi; Hernandez-Cadena, Leticia; Escamilla-Nuñez, Maria Consuelo; Sienra-Monge, Juan Jose; Ramírez-Aguilar, Matiana; Cortez-Lugo, Marlene; Holguin, Fernando; Diaz-Sánchez, David; Olin, Anna Carin; Romieu, Isabelle

    2008-01-01

    Background The biological mechanisms involved in inflammatory response to air pollution are not clearly understood. Objective In this study we assessed the association of short-term air pollutant exposure with inflammatory markers and lung function. Methods We studied a cohort of 158 asthmatic and 50 nonasthmatic school-age children, followed an average of 22 weeks. We conducted spirometric tests, measurements of fractional exhaled nitric oxide (FeNO), interleukin-8 (IL-8) in nasal lavage, and pH of exhaled breath condensate every 15 days during follow-up. Data were analyzed using linear mixed-effects models. Results An increase of 17.5 μg/m3 in the 8-hr moving average of PM2.5 levels (interquartile range) was associated with a 1.08-ppb increase in FeNO [95% confidence interval (CI), 1.01–1.16] and a 1.07-pg/mL increase in IL-8 (95% CI 0.98–1.19) in asthmatic children and a 1.16 pg/ml increase in IL-8 (95% CI, 1.00–1.36) in nonasthmatic children. The 5-day accumulated average of exposure to particulate matter < 2.5 μm in aerodynamic diamter (PM2.5) was significantly inversely associated with forced expiratory volume in 1 sec (FEV1) (p = 0.048) and forced vital capacity (FVC) (p = 0.012) in asthmatic children and with FVC (p = 0.021) in nonasthmatic children. FeNO and FEV1 were inversely associated (p = 0.005) in asthmatic children. Conclusions Exposure to PM2.5 resulted in acute airway inflammation and decrease in lung function in both asthmatic and nonasthmatic children. PMID:18560490

  8. Air pollution, airway inflammation, and lung function in a cohort study of Mexico City schoolchildren.

    Science.gov (United States)

    Barraza-Villarreal, Albino; Sunyer, Jordi; Hernandez-Cadena, Leticia; Escamilla-Nuñez, Maria Consuelo; Sienra-Monge, Juan Jose; Ramírez-Aguilar, Matiana; Cortez-Lugo, Marlene; Holguin, Fernando; Diaz-Sánchez, David; Olin, Anna Carin; Romieu, Isabelle

    2008-06-01

    The biological mechanisms involved in inflammatory response to air pollution are not clearly understood. In this study we assessed the association of short-term air pollutant exposure with inflammatory markers and lung function. We studied a cohort of 158 asthmatic and 50 nonasthmatic school-age children, followed an average of 22 weeks. We conducted spirometric tests, measurements of fractional exhaled nitric oxide (Fe(NO)), interleukin-8 (IL-8) in nasal lavage, and pH of exhaled breath condensate every 15 days during follow-up. Data were analyzed using linear mixed-effects models. An increase of 17.5 microg/m(3) in the 8-hr moving average of PM(2.5) levels (interquartile range) was associated with a 1.08-ppb increase in Fe(NO) [95% confidence interval (CI), 1.01-1.16] and a 1.07-pg/mL increase in IL-8 (95% CI 0.98-1.19) in asthmatic children and a 1.16 pg/ml increase in IL-8 (95% CI, 1.00-1.36) in nonasthmatic children. The 5-day accumulated average of exposure to particulate matter <2.5 microm in aerodynamic diamter (PM(2.5)) was significantly inversely associated with forced expiratory volume in 1 sec (FEV(1)) (p=0.048) and forced vital capacity (FVC) (p=0.012) in asthmatic children and with FVC (p=0.021) in nonasthmatic children. Fe(NO) and FEV(1) were inversely associated (p=0.005) in asthmatic children. Exposure to PM(2.5) resulted in acute airway inflammation and decrease in lung function in both asthmatic and nonasthmatic children.

  9. Human Primary Adipocytes Exhibit Immune Cell Function : Adipocytes Prime Inflammation Independent of Macrophages

    NARCIS (Netherlands)

    Meijer, Kees; de Vries, Marcel; Al-Lahham, Saad; Bruinenberg, Marcel; Weening, Desiree; Dijkstra, Martijn; Kloosterhuis, Niels; van der Leij, Roelof Jan; van der Want, Han; Kroesen, Bart-Jan; Vonk, Roel; Rezaee, Farhad

    2011-01-01

    Background: Obesity promotes inflammation in adipose tissue (AT) and this is implicated in pathophysiological complications such as insulin resistance, type 2 diabetes and cardiovascular disease. Although based on the classical hypothesis, necrotic AT adipocytes (ATA) in obese state activate AT

  10. New Indices of Endothelial Function Measured by Digital Thermal Monitoring of Vascular Reactivity: Data from 6084 Patients Registry

    Directory of Open Access Journals (Sweden)

    Morteza Naghavi

    2016-01-01

    Full Text Available Background. Endothelial function is viewed as a barometer of cardiovascular health and plays a central role in vascular reactivity. Several studies showed digital thermal monitoring (DTM as a simple noninvasive method to measure vascular reactivity that is correlated with atherosclerosis risk factors and coronary artery disease. Objectives. To further evaluate the relations between patient characteristics and DTM indices in a large patient registry. Methods. DTM measures were correlated with age, sex, heart rate, and systolic and diastolic blood pressure in 6084 patients from 18 clinics. Results. DTM vascular reactivity index (VRI was normally distributed and inversely correlated with age (r=-0.21, p<0.0001. Thirteen percent of VRI tests were categorized as poor vascular reactivity (VRI < 1.0, 70 percent as intermediate (1.0 ≤ VRI < 2.0, and 17 percent as good (VRI ≥ 2.0. Poor VRI (<1.0 was noted in 6% of <50 y, 10% of 50–70 y, and 18% of ≥70 y. In multiple linear regression analyses, age, sex, and diastolic blood pressure were significant but weak predictors of VRI. Conclusions. As the largest database of finger-based vascular reactivity measurement, this report adds to prior findings that VRI is a meaningful physiological marker and reflects a high level of residual risk found in patients currently under care.

  11. Functional Performance of Alzheimer's Disease and Vascular Dementia in Southern Taiwan

    Directory of Open Access Journals (Sweden)

    Mei-Yuh Shiau

    2006-09-01

    Full Text Available This study investigated the functional performance of two major subtypes of dementia, Alzheimer's disease (AD and vascular dementia (VaD, by the Functional Independence Measure (FIM, and to understand the need for assistance in performing activities of daily living. The subjects comprised 64AD and 21VaD patients who were recruited from two epidemiologic studies of dementia with a total of 3,931 community residents aged 65 years and above in southern Taiwan. The results showed that the severity of dementia was similar between the two groups. The mean score for AD was 82.7 and for VaD was 56.5 for total FIM (p < 0.05, 61.6 and 41.7 for the motor dimension (p < 0.05, and 21.1 and 15.7 for the cognitive dimension (p < 0.05. There were significant differences (p < 0.01 between AD and VaD in six FIM items and borderline or marginal significance (p < 0.05 in most of the FIM items. For AD patients, stairs, lower dressing, bathing, and tub/shower transfer were the most difficult items in the motor dimension, and it was memory in the cognitive dimension. For VaD patients, bathing, upper and lower dressing, and grooming were the most difficult items in the motor dimension, and it was problem solving in the cognitive dimension. VaD patients were more dependent on all FIM items and required more assistance than AD patients. The functional performances of dementia patients were significantly associated with dementia severity and subtypes, together accounting for 40% of the variability in total FIM. In conclusion, most dementia patients are dependent in daily activities and different types and severity of dementia lead to different disability profiles; individualized care is, therefore, most appropriate.

  12. Role of cardiac inflammation in right ventricular failure.

    Science.gov (United States)

    Sun, Xiao-Qing; Abbate, Antonio; Bogaard, Harm-Jan

    2017-10-01

    Right ventricular failure (RVF) is the main determinant of mortality in patients with pulmonary arterial hypertension (PAH). Although the exact pathophysiology underlying RVF remains unclear, inflammation may play an important role, as it does in left heart failure. Perivascular pulmonary artery and systemic inflammation is relatively well studied and known to contribute to the initiation and maintenance of the pulmonary vascular insult in PAH. However, less attention has been paid to the role of cardiac inflammation in RVF and PAH. Consistent with many other types of heart failure, cardiac inflammation, triggered by systemic and local stressors, has been shown in RVF patients as well as in RVF animal models. RV inflammation likely contributes to impaired RV contractility, maladaptive remodelling and a vicious circle between RV and pulmonary vascular injury. Although the potential to improve RV function through anti-inflammatory therapy has not been tested, this approach has been applied clinically in left ventricular failure patients, with variable success. Because inflammation plays a dual role in the development of both pulmonary vascular pathology and RVF, anti-inflammatory therapies may have a potential double benefit in patients with PAH and associated RVF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

  13. Acute impact of conventional and eccentric cycling on platelet and vascular function in patients with chronic heart failure.

    Science.gov (United States)

    Haynes, Andrew; Linden, Matthew D; Chasland, Lauren C; Nosaka, Kazunori; Maiorana, Andrew; Dawson, Ellen A; Dembo, Lawrence H; Naylor, Louise H; Green, Daniel J

    2017-06-01

    Evidence-based guidelines recommend exercise therapy for patients with chronic heart failure (CHF). Such patients have increased atherothrombotic risk. Exercise can transiently increase platelet activation and reactivity and decrease vascular function in healthy participants, although data in CHF are scant. Eccentric (ECC) cycling is a novel exercise modality that may be particularly suited to patients with CHF, but the acute impacts of ECC cycling on platelet and vascular function are currently unknown. Our null hypothesis was that ECC and concentric (CON) cycling, performed at matched external workloads, would not induce changes in platelet or vascular function in patients with CHF. Eleven patients with heart failure with reduced ejection fraction (HFrEF) took part in discrete bouts of ECC and CON cycling. Before and immediately after exercise, vascular function was assessed by measuring diameter and flow-mediated dilation (FMD) of the brachial artery. Platelet function was measured by the flow cytometric determination of glycoprotein IIb/IIIa activation and granule exocytosis in the presence and absence of platelet agonists. ECC cycling increased baseline artery diameter (pre: 4.0 ± 0.8 mm vs. post: 4.2 ± 0.7 mm; P = 0.04) and decreased FMD%. When changes in baseline artery diameter were accounted for, the decrease in FMD post-ECC cycling was no longer significant. No changes were apparent after CON. Neither ECC nor CON cycling resulted in changes to any platelet-function measures (all P > 0.05). These results suggest that both ECC and CON cycling, at a moderate intensity and short duration, can be performed by patients with HFrEF without detrimental impacts on vascular or platelet function. NEW & NOTEWORTHY This is the first evidence to indicate that eccentric (ECC) cycling can be performed relatively safely by patients with chronic heart failure (CHF), as it did not result in impaired vascular or platelet function compared with conventional cycling

  14. Treatment with high-dose n-3 PUFAs has no effect on platelet function, coagulation, metabolic status or inflammation in patients with atherosclerosis and type 2 diabetes.

    Science.gov (United States)

    Poreba, Malgorzata; Mostowik, Magdalena; Siniarski, Aleksander; Golebiowska-Wiatrak, Renata; Malinowski, Krzysztof Piotr; Haberka, Maciej; Konduracka, Ewa; Nessler, Jadwiga; Undas, Anetta; Gajos, Grzegorz

    2017-04-14

    Despite numerous studies on cardioprotective effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs), there is limited evidence for n-3 PUFA-mediated effects, especially at its higher dose, on cardiovascular risk in patients with type 2 diabetes (DM2) and established atherosclerosis. To investigate the effect of daily treatment with a higher dose (2 g) of n-3 PUFAs on platelet function, coagulation parameters, fibrin clot properties, markers of systemic inflammation and metabolic status, in patients with atherosclerotic vascular disease and DM2 who receive optimal medical therapy. We conducted a prospective, double-blind, placebo-controlled, randomized, double-center study, in which thrombin generation (plasma thrombogenic potential from automated thrombogram), fibrin clot properties (plasma fibrin clot permeability; lysis time), platelet aggregation (light transmission aggregometry with adenosine diphosphate and arachidonic acid used as agonists), HbA1c, insulin level, lipid profiles, leptin and adiponectin levels, as well as markers of systemic inflammation (i.e., hsCRP, IL-6, TNF-α, ICAM-1, VCAM-1, and myeloperoxidase) were determined at baseline and at 3 months after treatment with 2 g/day of n-3 PUFAs (n = 36) or placebo (n = 38). Moreover, we assessed serum fatty acids of the phospholipid fraction by gas chromatography both at baseline and at the end of the study. Majority of patients were treated with optimal medical therapy and achieved recommended treatment targets. Despite higher serum levels of eicosapentaenoic acid (EPA) (by 204%; p acid (DHA) (by 62%; p coagulation, metabolic, and inflammatory status when measured with the specified tests. The study was registered in ClinicalTrials.gov; identifier: NCT02178501. Registration date: April 12, 2014.

  15. Role of olmesartan in combination therapy in blood pressure control and vascular function

    Directory of Open Access Journals (Sweden)

    Carlos M Ferrario

    2010-08-01

    Full Text Available Carlos M Ferrario, Ronald D SmithWake Forest University School of Medicine, Winston-Salem, North Carolina, USAAbstract: Angiotensin receptor blockers have emerged as a first-line therapy in the management of hypertension and hypertension-related comorbidities. Since national and international guidelines have stressed the need to control blood pressure to <140/90 mmHg in uncomplicated hypertension and <130/80 mmHg in those with associated comorbidities such as diabetes or chronic kidney disease, these goal blood pressures can only be achieved through combination therapy. Of several drugs that can be effectively combined to attain the recommended blood pressure goals, fixed-dose combinations of angiotensin receptor blockers and the calcium channel blocker amlodipine provide additive antihypertensive effects associated with a safe profile and increased adherence to therapy. In this article, we review the evidence regarding the beneficial effects of renin–angiotensin system blockade with olmesartan medoxomil and amlodipine in terms of blood pressure control and improvement of vascular function and target organ damage.Keywords: amlodipine, angiotensin receptor blockers, angiotensin-converting enzyme 2, hypertension, renin–angiotensin system

  16. Inflammation, Metabolic Dysregulation, and Pulmonary Function among Obese Urban Adolescents with Asthma

    Science.gov (United States)

    Fraser, Sasha; Oh, Jamie; Huber, Ashley M.; Schulman, Yael; Bhagtani, Renuka H.; Khan, Zeeshan S.; Tesfa, Lydia; Hall, Charles B.; Macian, Fernando

    2015-01-01

    Rationale: Insulin resistance and low high-density lipoprotein (HDL) are associated with pulmonary morbidity, including asthma, but the underlying mechanisms are not well elucidated. Objectives: To investigate whether systemic inflammation underlies the association of metabolic abnormalities with pulmonary function among urban adolescents. Methods: Th-cell responses and monocyte subsets, and their association with serum homeostatic model assessment of insulin resistance (HOMA-IR) and HDL, and pulmonary function were quantified in 168 adolescents, including 42 obese subjects with asthma, 42 normal-weight subjects with asthma, 40 obese subjects without asthma, and 44 healthy control subjects. Th-cell responses (Th1 [CD4+IFNγ+] and Th2 [CD4+IL4+] cells) to stimulation with phytohemagglutinin, leptin, and dust mite, and classical (CD14+CD16−), resident (CD14+CD16+), and patrolling (CD14dimCD16+) monocytes, and their C-C chemokine receptor type-2 (CCR2) expression were quantified by flow cytometry. Measurements and Main Results: Th1/Th2 ratio to all three stimuli was higher in obese subjects with asthma than normal-weight subjects with asthma and directly correlated with HOMA-IR. Classical monocytes inversely associated with Th1/Th2 ratio to phytohemagglutinin (r = −0.43; P = 0.01) and directly with Asthma Control Test score (β = 1.09; P = 0.04), while patrolling monocytes correlated with Composite Asthma Severity Index score (β = 1.11; P = 0.04) only among obese subjects with asthma. HDL was inversely associated with patrolling monocytes and directly associated with CCR2 expression on resident monocytes. CCR2 expression on patrolling monocytes predicted residual volume (RV), RV/TLC ratio, and FRC, after adjusting for HDL, but not after adjusting for body mass index. Association of Th1/Th2 ratio with RV, FRC, and inspiratory capacity was attenuated after adjusting for HOMA-IR. Conclusions: Th1 polarization and monocyte activation among

  17. Acute coronary syndrome and acute kidney injury: role of inflammation in worsening renal function.

    Science.gov (United States)

    Ortega-Hernández, Jorge; Springall, Rashidi; Sánchez-Muñoz, Fausto; Arana-Martinez, Julio-C; González-Pacheco, Héctor; Bojalil, Rafael

    2017-07-26

    , Na + , K + , WBC, age, body mass index, GRACE, SBP, mean-BP and Hb. Inflammation and its components play an important role in the worsening of renal function in ACS. IL-10, ET-1, IL-1β, TnI, RvD1 and LxA4 represent mediators that might be associated with ACS-AKI. IL-6, ET-1, NT-ProBNP might represent crossroads for several physiopathological pathways involved in "de novo cardiac injury leading to de novo kidney injury".

  18. [Effects of milk and coenzyme Q10 on the interference of acrylonitrile on vascular endothelial functions].

    Science.gov (United States)

    Guo, Jin; Wang, Wei-qun; Gong, Hui

    2011-04-26

    To explore the influences of milk or coenzyme Q(10) pretreatment to acrylonitrile on vascular endothelial functions in rats. A total of 80 rats were randomly divided into 4 groups: control group (Con), acrylonitrile exposure group (ACN), milk pretreatment group (M + ACN) and coenzyme Q(10) pretreatment group (Q(10) + ACN). The experiment was conducted by the method of gavage exposure in rats. Control group was exposed to corn oil; acrylonitrile was administered to other three groups at the doses of 25 mg/kg. The M + ACN and Q(10) + ACN groups were pretreated by milk or coenzyme Q(10) at 30 minutes before acrylonitrile exposure. After a 12-week exposure, the activities of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) were measured in serum and aortal tissues. As compared with Con group [(21.9 ± 1.6) U/ml], the activity of blood serum iNOS was higher in ACN, M + ACN and Q(10) + ACN groups [(42.9 ± 2.5) U/ml, (26.5 ± 4.4) U/ml, (26.7 ± 3.3) U/ml, P < 0.05]. As compared with Con group [(0.540 ± 0.028) U/mg protein], the activity of aortal iNOS was higher in ACN, M + ACN and Q(10) + ACN groups [(0.812 ± 0.008), (0.773 ± 0.019), (0.622 ± 0.013) U/mg protein, (P < 0.05)]. Furthermore the activity of aortal eNOS in Q(10) + ACN group [(0.471 ± 0.011) U/mg protein] was higher than Con, ACN or M + ACN group [(0.371 ± 0.029), (0.380 ± 0.016), (0.425 ± 0.020) U/mg protein, P < 0.05]. Chronic administration of ACN by gavages results in vascular endothelial dysfunctions. Milk and coenzyme Q(10) pretreatment reduce this effect in rats.

  19. Functional and molecular mapping of uncoupling between vascular permeability and loss of vascular maturation in ovarian carcinoma xenografts: the role of stroma cells in tumor angiogenesis.

    Science.gov (United States)

    Gilad, Assaf A; Israely, Tomer; Dafni, Hagit; Meir, Gila; Cohen, Batya; Neeman, Michal

    2005-11-01

    Maintaining homogeneous perfusion in tissues undergoing remodeling and vascular expansion requires tight orchestration of the signals leading to endothelial sprouting and subsequent recruitment of perivascular contractile cells and vascular maturation. This regulation, however, is frequently disrupted in tumors. We previously demonstrated the role of tumor-associated myofibroblasts in vascularization and exit from dormancy of human ovarian carcinoma xenografts in nude mice. The aim of this work was to determine the contribution of stroma- and tumor cell-derived angiogenic growth factors to the heterogeneity of vascular permeability and maturation in MLS human ovarian carcinoma tumors. We show by RT-PCR and by in situ hybridization that VEGF was expressed by the tumor cells, while angiopoietin-1 and -2 were expressed only by the infiltrating host stroma cells. Vascular maturation was detected in vivo by vasoreactivity to hypercapnia, measured by BOLD contrast MRI and validated by immunostaining of histologic sections to alpha-smooth muscle actin. Vascular permeability was measured in vivo by dynamic contrast-enhanced MRI using albumin-based contrast material and validated in histologic sections by fluorescent staining of the biotinylated contrast material. MRI as well as histologic correlation maps between vascular maturation and vascular permeability revealed a wide range of vascular phenotypes, in which the distribution of vascular maturation and vasoreactivity did not overlap spatially with reduced permeability. The large heterogeneity in the degree of vascular maturation and permeability is consistent with the differential expression pattern of VEGF and angiopoietins during tumor angiogenesis.

  20. Differential effects of hormone therapy on serotonin, vascular function and mood in the KEEPS.

    Science.gov (United States)

    Raz, L; Hunter, L V; Dowling, N M; Wharton, W; Gleason, C E; Jayachandran, M; Anderson, L; Asthana, S; Miller, V M

    2016-01-01

    Serotonin (5-hydroxytryptamine, 5-HT) is modulated by sex steroid hormones and affects vascular function and mood. In the Kronos Early Estrogen Prevention Cognitive and Affective Ancillary Study (KEEPS-Cog), women randomized to oral conjugated equine estrogens (oCEE) showed greater benefit on affective mood states than women randomized to transdermal 17β-estradiol (tE2) or placebo (PL). This study examined the effect of these treatments on the platelet content of 5-HT as a surrogate measure of 5-HT synthesis and uptake in the brain. The following were measured in a subset (n = 79) of women enrolled in KEEPS-Cog: 5-HT by ELISA, carotid intima-medial thickness (CIMT) by ultrasound, endothelial function by reactive hyperemic index (RHI), and self-reported symptoms of affective mood states by the Profile of Mood States (POMS) questionnaire. Mean platelet content of 5-HT increased by 107.0%, 84.5% and 39.8%, in tE2, oCEE and PL groups, respectively. Platelet 5-HT positively correlated with estrone in the oCEE group and with 17β- estradiol in the tE2 group. Platelet 5-HT showed a positive association with RHI, but not CIMT, in the PL and oCEE groups. Reduction in mood scores for depression-dejection and anger-hostility was associated with elevations in platelet 5-HT only in the oCEE group (r = -0.5, p = 0.02). Effects of oCEE compared to tE2 on RHI and mood may be related to mechanisms involving platelet, and perhaps neuronal, uptake and release of 5-HT and reflect conversion of estrone to bioavailable 17β-estradiol in platelets and the brain.

  1. One Minute of Marijuana Secondhand Smoke Exposure Substantially Impairs Vascular Endothelial Function.

    Science.gov (United States)

    Wang, Xiaoyin; Derakhshandeh, Ronak; Liu, Jiangtao; Narayan, Shilpa; Nabavizadeh, Pooneh; Le, Stephenie; Danforth, Olivia M; Pinnamaneni, Kranthi; Rodriguez, Hilda J; Luu, Emmy; Sievers, Richard E; Schick, Suzaynn F; Glantz, Stanton A; Springer, Matthew L

    2016-07-27

    Despite public awareness that tobacco secondhand smoke (SHS) is harmful, many people still assume that marijuana SHS is benign. Debates about whether smoke-free laws should include marijuana are becoming increasingly widespread as marijuana is legalized and the cannabis industry grows. Lack of evidence for marijuana SHS causing acute cardiovascular harm is frequently mistaken for evidence that it is harmless, despite chemical and physical similarity between marijuana and tobacco smoke. We investigated whether brief exposure to marijuana SHS causes acute vascular endothelial dysfunction. We measured endothelial function as femoral artery flow-mediated dilation (FMD) in rats before and after exposure to marijuana SHS at levels similar to real-world tobacco SHS conditions. One minute of exposure to marijuana SHS impaired FMD to a comparable extent as impairment from equal concentrations of tobacco SHS, but recovery was considerably slower for marijuana. Exposure to marijuana SHS directly caused cannabinoid-independent vasodilation that subsided within 25 minutes, whereas FMD remained impaired for at least 90 minutes. Impairment occurred even when marijuana lacked cannabinoids and rolling paper was omitted. Endothelium-independent vasodilation by nitroglycerin administration was not impaired. FMD was not impaired by exposure to chamber air. One minute of exposure to marijuana SHS substantially impairs endothelial function in rats for at least 90 minutes, considerably longer than comparable impairment by tobacco SHS. Impairment of FMD does not require cannabinoids, nicotine, or rolling paper smoke. Our findings in rats suggest that SHS can exert similar adverse cardiovascular effects regardless of whether it is from tobacco or marijuana. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  2. Effect of moderate- versus high-intensity exercise on vascular function, biomarkers and quality of life in heart transplant recipients

    DEFF Research Database (Denmark)

    Dall, Christian H; Gustafsson, Finn; Christensen, Stefan B

    2015-01-01

    BACKGROUND: Growing evidence in long-term treatment of heart transplant (HTx) recipients indicates effects of high-intensity interval training (HIIT) on several parameters, including oxygen uptake, vascular function and psychological distress. In this study we compare the effect of HIIT vs...... continued moderate training (CON) on vascular function, biomarkers and health-related quality of life (HRQoL) in HTx recipients. METHODS: A randomized, controlled crossover trial of stable HTx recipients >12 months after transplantation was done on patients with 12 weeks of HIIT or 12 weeks of CON, followed...... by a 5-month washout and crossover. Outcomes included endothelial function, arterial stiffness, biomarkers, HRQoL and markers of anxiety and depression. RESULTS: Sixteen HTx recipients (mean age 52 years, 75% male) completed the study. HIIT increased VO2peak more than CON (between-group difference, p

  3. Leukocyte Subtype Counts and Its Association with Vascular Structure and Function in Adults with Intermediate Cardiovascular Risk. MARK Study

    Science.gov (United States)

    Gomez-Sanchez, Leticia; García-Ortiz, Luis; Recio-Rodríguez, José I.; Patino-Alonso, Maria C.; Agudo-Conde, Cristina; Rigo, Fernando; Ramos, Rafel; Martí, Ruth; Gomez-Marcos, Manuel A.

    2015-01-01

    Objectives We investigated the relationship between leukocyte subtype counts and vascular structure and function based on carotid intima-media thickness, pulse wave velocity, central augmentation index and cardio-ankle vascular index by gender in intermediate cardiovascular risk patients. Methods This study analyzed 500 subjects who were included in the MARK study, aged 35 to 74 years (mean: 60.3±8.4), 45.6% women. Measurement: Brachial ankle Pulse Wave Velocity (ba-PWV) estimate by equation, Cardio-AnkleVascular Index (CAVI) using the VaSera device and Carotid ultrasound was used to measure carotid Intima Media Thickness (IMT). The Mobil-O-Graph was used to measure the Central Augmentation Index (CAIx). Results Total leukocyte, neutrophil and monocyte counts were positively correlated with IMT (p leukocyte counts and vascular structure and function, although small, may be different by gender. In men, the neutrophil count was positively correlated with IMT and in women, the monocyte count with CAIx, in a large sample of intermediate-risk patients. These association were maintained after adjusting for age and other confounders. Trial Registration ClinicalTrials.gov NCT01428934 PMID:25885665

  4. Subfailure overstretch injury leads to reversible functional impairment and purinergic P2X7 receptor activation in intact vascular tissue

    Directory of Open Access Journals (Sweden)

    Weifeng Luo

    2016-09-01

    Full Text Available Vascular stretch injury is associated with blunt trauma, vascular surgical procedures, and harvest of human saphenous vein for use in vascular bypass grafting. A model of subfailure overstretch in rat abdominal aorta was developed to characterize surgical vascular stretch injury. Longitudinal stretch of rat aorta was characterized ex vivo. Stretch to the haptic endpoint where the tissues would no longer lengthen, occurred at twice the resting length. The stress produced at this length was greater than physiologic mechanical forces but well below the level of mechanical disruption. Functional responses were determined in a muscle bath and this subfailure overstretch injury led to impaired smooth muscle function that was partially reversed by treatment with purinergic receptor (P2X7R antagonists. These data suggest that vasomotor dysfunction caused by subfailure overstretch injury may be due to activation of P2X7R. These studies have implications for our understanding of mechanical stretch injury of blood vessels and offer novel therapeutic opportunities.

  5. Endothelial cell senescence with aging in healthy humans: prevention by habitual exercise and relation to vascular endothelial function.

    Science.gov (United States)

    Rossman, Matthew J; Kaplon, Rachelle E; Hill, Sierra D; McNamara, Molly N; Santos-Parker, Jessica R; Pierce, Gary L; Seals, Douglas R; Donato, Anthony J

    2017-11-01

    Cellular senescence is emerging as a key mechanism of age-related vascular endothelial dysfunction, but evidence in healthy humans is lacking. Moreover, the influence of lifestyle factors such as habitual exercise on endothelial cell (EC) senescence is unknown. We tested the hypothesis that EC senescence increases with sedentary, but not physically active, aging and is associated with vascular endothelial dysfunction. Protein expression (quantitative immunofluorescence) of p53, a transcription factor related to increased cellular senescence, and the cyclin-dependent kinase inhibitors p21 and p16 were 116%, 119%, and 128% greater (all P 0.05) in venous ECs from older exercising adults (57 ± 1 yr, n = 13). Furthermore, venous EC protein levels of p53 ( r  = -0.49, P = 0.003), p21 ( r  = -0.38, P = 0.03), and p16 ( r  = -0.58, P = 0.002) were inversely associated with vascular endothelial function (brachial artery flow-mediated dilation). Similarly, protein expression of p53 and p21 was 26% and 23% higher (both P 0.05) in older habitually exercising adults (59 ± 1 yr, n = 14). These data indicate that EC senescence is associated with sedentary aging and is linked to endothelial dysfunction. Moreover, these data suggest that prevention of EC senescence may be one mechanism by which aerobic exercise protects against endothelial dysfunction with age. NEW & NOTEWORTHY Our study provides novel evidence in humans of increased endothelial cell senescence with sedentary aging, which is associated with impaired vascular endothelial function. Furthermore, our data suggest an absence of age-related increases in endothelial cell senescence in older exercising adults, which is linked with preserved vascular endothelial function. Copyright © 2017 the American Physiological Society.

  6. A Collaborative Research System for Functional Outcomes Following Wartime Extremity Vascular Injury

    Science.gov (United States)

    2012-01-01

    transtibial , or above the ankle, in the lower extremity and above the forearm in the upper extremity. Secondary amputations are defined as...Rasmussen, MD, Fort Sam Houston, Texas Vascular injury with hemorrhage and ischemia is a signifi-cant cause of battlefield morbidity (i.e., amputation ...this cohort, extremity vascular injuries are confirmed, and method of management (primary amputation , ligation, repair, etc.) was recorded. When

  7. Periodontal inflammation in relation to cognitive function in an older adult danish population

    DEFF Research Database (Denmark)

    Kamer, Angela R; Morse, Douglas E; Holm-Pedersen, Poul

    2012-01-01

    Inflammation plays a significant role in Alzheimer's disease (AD) pathogenesis. Studies have shown that systemic, peripheral infections affect AD patients. Cognitive dysfunction is a consistent finding in AD and periodontal disease is a chronic, peripheral infection often resulting in tooth loss....... We hypothesized that older adults with periodontal inflammation (PI) or many missing teeth would show impaired cognition compared to subjects without PI or with few missing teeth, and among subjects with PI, those with many missing teeth would show impaired cognition compared to those with few...

  8. How inflammation underlies physical and organ function in acutely admitted older medical patients

    DEFF Research Database (Denmark)

    Klausen, Henrik Hedegaard; Bodilsen, Ann Christine; Petersen, Janne

    2017-01-01

    OBJECTIVES: To investigate whether systemic inflammation in acutely admitted older medical patients (age >65 years) is associated with physical performance and organ dysfunction. Organ dysfunction´s association with physical performance, and whether these associations are mediated by systemic...... inflammation, was also investigated. METHODS: A cross-sectional study in an Emergency Department. Physical performance was assessed by handgrip strength and de Morton Mobility Index (DEMMI), and organ dysfunction by FI-OutRef, the number of standard blood tests outside the reference range. Systemic...... physical performance measures (pphysical performance (all p

  9. Altered Functional Connectivity in Patients with Subcortical Vascular Cognitive Impairment--A Resting-State Functional Magnetic Resonance Imaging Study.

    Directory of Open Access Journals (Sweden)

    Weina Ding

    Full Text Available Recent neuroimaging studies have shown that people with subcortical vascular cognitive impairment (sVCI have structural and functional abnormalities in the frontal lobe and subcortical brain sites. In this study, we used seed-based resting-state functional connectivity (rsFC analysis and voxel-mirrored homotopic connectivity (VMHC techniques to investigate the alteration of rsFC in patients with sVCI. rsFC and structural magnetic resonance images were acquired for 51 patients with subcortical cerebrovascular disease. All patients were subdivided based on cognitive status into 29 with sVCI and 22 controls; patient characteristics were matched. rsFC of the posterior cingulate cortex (PCC and VMHC were calculated separately, and rsFC of the PCC and VMHC between the two groups were compared. The regions showing abnormal rsFC of the PCC or VMHC in sVCI patients were adopted as regions of interest for correlation analyses. Our results are as follows: The patients with sVCI exhibited increases in rsFC in the left middle temporal lobe, right inferior temporal lobe and left superior frontal gyrus, and significant decreases in rsFC of the left thalamus with the PCC. sVCI patients showed a significant deficit in VMHC between the bilateral lingual gyrus, putamen, and precentral gyrus. Additionally, the z-memory score was significantly positively associated with connectivity between the left thalamus and the PCC (r = 0.41, p = 0.03, uncorrected in the sVCI group. Our findings suggest that the frontal lobe and subcortical brain sites play an important role in the pathogenesis of sVCI. Furthermore, rsFC between the left thalamus and the PCC might indicate the severity of sVCI.

  10. Effect of long-term Vitamin C intake on vascular endothelial function in diabetic children and adolescents: A pilot study

    Directory of Open Access Journals (Sweden)

    Mohammadreza Sabri

    2016-01-01

    Full Text Available Background: This study attempted to determine the effects of long-term use of Vitamin C on vascular endothelial function. Materials and Methods: During a pilot clinical trial study conducted at Imam Hussein Hospital (Isfahan in 2014–2015, a total of forty diabetic patients were selected and then assigned randomly into two twenty-subject groups receiving Vitamin C and placebo tablets. The patients were treated with Vitamin C or placebo for 6 months. All patients were examined through echocardiography in terms of cardiac function before and after treatment. To evaluate the endothelial function (flow-mediated dilatation [FMD], intima-media thickness, they underwent arterial Doppler. Moreover, the chemical indices of vascular function were tested through intercellular adhesion molecule and vascular cell adhesion molecule (VCAM. Finally, the results were compared between the two groups. Results: Based on the results, the mean left ventricular mass significantly reduced after the intervention in the group treated with Vitamin C (from 76.35 ± 25.6–68.62 ± 22.66; P = 0.015 while there was no significant difference observed in the control group (from 67.58 ± 25.38–71.63 ± 26.84; P = 0.19 but no statistically difference between the two groups-based repeated measures ANOVA test (P = 0.6. In addition, the mean of VCAM changes was significantly difference between the two groups (P < 0.001. Conclusion: Long-term use of Vitamin C in diabetic patients can improve certain echocardiographic parameters such as ejection fraction, fractional shortening, and FMD, which in turn enhances vascular endothelial function.

  11. Evaluation of the relationship between renal function and renal volume-vascular indices using 3D power Doppler ultrasound

    Energy Technology Data Exchange (ETDEWEB)

    Cansu, Aysegul, E-mail: drcansu@gmail.com; Kupeli, Ali; Kul, Sibel; Eyuboglu, Ilker; Oguz, Sukru; Ozturk, Mehmet Halil; Dinc, Hasan

    2014-07-15

    Purpose: To investigate the relationship between renal function and total renal volume-vascular indices using 3D power Doppler ultrasound (3DPDUS). Materials and methods: One hundred six patients with hypertensive proteinuric nephropathy (HPN) (49 male, 57 female) and 65 healthy controls (32 male, 33 female) were evaluated prospectively using 3DPDUS. Total renal volume (RV), vascularization index (VI), flow index (FI) and vascularization flow index (VFI) were calculated using Virtual Organ Computer-aided Analysis (VOCAL). The estimated glomerular filtration rates (GFRs) of the patients with HPN and the control group were calculated. The patients with HPN were divided into two groups on the basis of GFR, normal (≥90) or reduced (<90). Differences between groups were compared using ANOVA. Correlations between GFR, renal volume and vascular indices were analyzed using Pearson's correlation analysis. Significance was set at p < 0.05. Results: The mean total RV, VI, FI and VFI values in the reduced GFR, normal GFR and control groups were RV (ml): 234.7, 280.7 and 294.6; VI: 17.6, 27.6 and 46.8; FI: 79.1, 88.7 and 93.9 and VFI: 7.1, 12.7 and 23.8. There were statistically significant differences between the groups (p < 0.001). Total RVs and vascular indices exhibited significant correlations with estimated GFR (r = 0.53–0.59, p < 0.001) Conclusion: Three-dimensional power Doppler ultrasound is a reliable predictive technique in renal function analysis.

  12. Changes in vascular plant functional types drive carbon cycling in peatlands

    Science.gov (United States)

    Zeh, Lilli; Bragazza, Luca; Erhagen, Björn; Limpens, Juul; Kalbitz, Karsten

    2016-04-01

    Northern peatlands store a large organic carbon (C) pool that is highly exposed to future environmental changes with consequent risk of releasing enormous amounts of C. Biotic changes in plant community structure and species abundance might have an even stronger impact on soil organic C dynamics in peatlands than the direct effects of abiotic changes. Therefore, a sound understanding of the impact of vegetation dynamics on C cycling will help to better predict the response of peatlands to environmental changes. Here, we aimed to assess the role of plant functional types (PFTs) in affecting peat decomposition in relation to climate warming. To this aim, we selected two peatlands at different altitude (i.e. 1300 and 1700 m asl) on the south-eastern Alps of Italy. The two sites represent a contrast in temperature, overall vascular plant biomass and relative ericoids abundance, with the highest biomass and ericoids occurrence at the low latitude. Within the sites we selected 20 plots of similar microtopographical position and general vegetation type (hummocks). All plots contained both graminoids and ericoids and had a 100% cover of Sphagnum mosses. The plots were subjected to four treatments (control, and three clipping treatments) in which we selectively removed aboveground biomass of ericoids, graminoids or both to explore the contribution of the different PFTs for soil respiration (n=5) and peat chemistry. Peat chemical composition was determined by the analysis of C and N and their stable isotopes in association with pyrolysis GC/MS. Soil respiration was measured after clipping with a Licor system. Preliminary findings suggest that peat decomposition pathway and rate depend on plant species composition and particularly on differences in root activity between PFTs. Finally, this study underlines the importance of biotic drivers to predict the effects of future environmental changes on peatland C cycling.

  13. Fetal cardiac function after labetalol or pindolol for maternal hypertension in a sheep model of increased placental vascular resistance.

    Science.gov (United States)

    Erkinaro, Tiina; Haapsamo, Mervi; Kavasmaa, Tomi; Mäkikallio, Kaarin; Acharya, Ganesh; Räsänen, Juha

    2013-01-01

    We hypothesized that labetalol and pindolol have no detrimental effects on fetal cardiac function and pulmonary hemodynamics when administered for norepinephrine-induced maternal hypertension in a chronic sheep model of increased placental vascular resistance. Specifically, we investigated the effects of labetalol and pindolol on fetal cardiopulmonary responses to acute hypoxemia. Twenty chronically instrumented near-term ewes with increased placental vascular resistance after placental embolization were anesthetized and randomized to receive labetalol or pindolol for norepinephrine-induced hypertension. Thereafter, maternal inspiratory oxygen fraction was decreased to induce fetal hypoxemia. At the end of each phase, fetal hemodynamics were assessed by Doppler ultrasonography. The data were analyzed using repeated measures ANOVA. Maternal administration of norepinephrine had no effect on fetal hemodynamics. Pindolol decreased fetal heart rate and weight-indexed left ventricular cardiac output and increased pulmonary vascular impedances, while labetalol had no effect on these parameters. During hypoxemia, fetal heart rate increased to baseline in the pindolol group and pulmonary vascular impedances increased in the labetalol group, with no changes in fetal cardiac outputs. Pindolol decreased fetal left ventricular cardiac output and induced vasoconstriction in the pulmonary vasculature, but neither pindolol nor labetalol significantly modified fetal cardiopulmonary responses to acute hypoxemia. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  14. Chronic Stress Improves NO- and Ca2+ Flux-Dependent Vascular Function: A Pharmacological Study

    Directory of Open Access Journals (Sweden)

    Thiago Bruder-Nascimento

    2015-03-01

    Full Text Available Background: Stress is associated with cardiovascular diseases. Objective: This study aimed at assessing whether chronic stress induces vascular alterations, and whether these modulations are nitric oxide (NO and Ca2+ dependent. Methods: Wistar rats, 30 days of age, were separated into 2 groups: control (C and Stress (St. Chronic stress consisted of immobilization for 1 hour/day, 5 days/week, 15 weeks. Systolic blood pressure was assessed. Vascular studies on aortic rings were performed. Concentration-effect curves were built for noradrenaline, in the presence of L-NAME or prazosin, acetylcholine, sodium nitroprusside and KCl. In addition, Ca2+ flux was also evaluated. Results: Chronic stress induced hypertension, decreased the vascular response to KCl and to noradrenaline, and increased the vascular response to acetylcholine. L-NAME blunted the difference observed in noradrenaline curves. Furthermore, contractile response to Ca2+ was decreased in the aorta of stressed rats. Conclusion: Our data suggest that the vascular response to chronic stress is an adaptation to its deleterious effects, such as hypertension. In addition, this adaptation is NO- and Ca2+-dependent. These data help to clarify the contribution of stress to cardiovascular abnormalities. However, further studies are necessary to better elucidate the mechanisms involved in the cardiovascular dysfunction associated with stressors. (Arq Bras Cardiol. 2014; [online].ahead print, PP.0-0

  15. Chronic Stress Improves NO- and Ca2+ Flux-Dependent Vascular Function: A Pharmacological Study

    Energy Technology Data Exchange (ETDEWEB)

    Bruder-Nascimento, Thiago, E-mail: bruderthiago@usp.br [Departamento de Farmacologia - Instituto de Biociências de Botucatu - Universidade do Estado de São Paulo (UNESP), Botucatu, São Paulo (Brazil); Departamento de Clínica Médica - Faculdade de Medicina de Botucatu - Universidade do Estado de São Paulo (UNESP), Botucatu, São Paulo (Brazil); Campos, Dijon Henrique Salome [Departamento de Clínica Médica - Faculdade de Medicina de Botucatu - Universidade do Estado de São Paulo (UNESP), Botucatu, São Paulo (Brazil)

    2015-03-15

    Stress is associated with cardiovascular diseases. This study aimed at assessing whether chronic stress induces vascular alterations, and whether these modulations are nitric oxide (NO) and Ca2+ dependent. Wistar rats, 30 days of age, were separated into 2 groups: control (C) and Stress (St). Chronic stress consisted of immobilization for 1 hour/day, 5 days/week, 15 weeks. Systolic blood pressure was assessed. Vascular studies on aortic rings were performed. Concentration-effect curves were built for noradrenaline, in the presence of L-NAME or prazosin, acetylcholine, sodium nitroprusside and KCl. In addition, Ca{sup 2+} flux was also evaluated. Chronic stress induced hypertension, decreased the vascular response to KCl and to noradrenaline, and increased the vascular response to acetylcholine. L-NAME blunted the difference observed in noradrenaline curves. Furthermore, contractile response to Ca{sup 2+} was decreased in the aorta of stressed rats. Our data suggest that the vascular response to chronic stress is an adaptation to its deleterious effects, such as hypertension. In addition, this adaptation is NO- and Ca{sup 2+}-dependent. These data help to clarify the contribution of stress to cardiovascular abnormalities. However, further studies are necessary to better elucidate the mechanisms involved in the cardiovascular dysfunction associated with stressors. (Arq Bras Cardiol. 2014; [online].ahead print, PP.0-0)

  16. The influence of perivascular adipose tissue on vascular homeostasis.

    Science.gov (United States)

    Szasz, Theodora; Bomfim, Gisele Facholi; Webb, R Clinton

    2013-01-01

    The perivascular adipose tissue (PVAT) is now recognized as an active contributor to vascular function. Adipocytes and stromal cells contained within PVAT are a source of an ever-growing list of molecules with varied paracrine effects on the underlying smooth muscle and endothelial cells, including adipokines, cytokines, reactive oxygen species, and gaseous compounds. Their secretion is regulated by systemic or local cues and modulates complex processes, including vascular contraction and relaxation, smooth muscle cell proliferation and migration, and vascular inflammation. Recent evidence demonstrates that metabolic and cardiovascular diseases alter the morphological and secretory characteristics of PVAT, with notable consequences. In obesity and diabetes, the expanded PVAT contributes to vascular insulin resistance. PVAT-derived cytokines may influence key steps of atherogenesis. The physiological anticontractile effect of PVAT is severely diminished in hypertension. Above all, a common denominator of the PVAT dysfunction in all these conditions is the immune cell infiltration, which triggers the subsequent inflammation, oxidative stress, and hypoxic processes to promote vascular dysfunction. In this review, we discuss the currently known mechanisms by which the PVAT influences blood vessel function. The important discoveries in the study of PVAT that have been made in recent years need to be further advanced, to identify the mechanisms of the anticontractile effects of PVAT, to explore the vascular-bed and species differences in PVAT function, to understand the regulation of PVAT secretion of mediators, and finally, to uncover ways to ameliorate cardiovascular disease by targeting therapeutic approaches to PVAT.

  17. Vascular function assessed by passive leg movement and flow-mediated dilation: initial evidence of construct validity.

    Science.gov (United States)

    Rossman, Matthew J; Groot, H Jonathan; Garten, Ryan S; Witman, Melissa A H; Richardson, Russell S

    2016-11-01

    The vasodilatory response to passive leg movement (PLM) appears to provide a novel, noninvasive assessment of vascular function. However, PLM has yet to be compared with the established noninvasive assessment of vascular health, flow-mediated dilation (FMD). Therefore, as an initial evaluation of the construct validity of PLM and upright seated and supine PLM as well as brachial (BA) and superficial femoral (SFA) artery FMDs were performed in 10 young (22 ± 1) and 30 old (73 ± 2) subjects. During upright seated PLM, the peak change in leg blood flow (ΔLBF) and leg vascular conductance (ΔLVC) was significantly correlated with BA (r = 0.57 and r = 0.66) and SFA (r = 0.44 and r = 0.41, ΔLBF and ΔLVC, respectively) FMD. Furthermore, although the relationships were not as strong, the supine PLM response was also significantly correlated with BA (r = 0.38 and r = 0.35) and SFA (r = 0.39 and r = 0.35, ΔLBF and ΔLVC, respectively) FMD. Examination of the young and old separately, however, revealed that significant relationships persisted in both groups only for the upright seated PLM response and BA FMD (young: r = 0.73 and r = 0.77; old: r = 0.35 and r = 0.45, ΔLBF and ΔLVC, respectively). Normalizing FMD for shear rate during PLM abrogated all significant relationships between the PLM and FMD response, suggesting a role for nitric oxide (NO) in these associations. Collectively, these data indicate that PLM, particularly upright seated PLM, likely provides an index of vascular health analogous to the traditional FMD test. Given the relative ease of PLM implementation, these data have important positive implications for PLM as a clinical vascular health assessment.

  18. VASCULAR DEMENTIA

    Directory of Open Access Journals (Sweden)

    Maria Alekseyevna Cherdak

    2010-01-01

    vascular cognitive disorders and vascular dementia (VD. The heterogeneity of vascular cognitive disorders, concurrence of vascular and neurodegenerative diseases are discussed. Data from studies of specific therapy for VD are given.

  19. Functional up-regulation of Nav1.8 sodium channel in Aβ afferent fibers subjected to chronic peripheral inflammation

    Science.gov (United States)

    2014-01-01

    Background Functional alterations in the properties of Aβ afferent fibers may account for the increased pain sensitivity observed under peripheral chronic inflammation. Among the voltage-gated sodium channels involved in the pathophysiology of pain, Nav1.8 has been shown to participate in the peripheral sensitization of nociceptors. However, to date, there is no evidence for a role of Nav1.8 in controlling Aβ-fiber excitability following persistent inflammation. Methods Distribution and expression of Nav1.8 in dorsal root ganglia and sciatic nerves were qualitatively or quantitatively assessed by immunohistochemical staining and by real time-polymerase chain reaction at different time points following complete Freund’s adjuvant (CFA) administration. Using a whole-cell patch-clamp configuration, we further determined both total INa and TTX-R Nav1.8 currents in large-soma dorsal root ganglia (DRG) neurons isolated from sham or CFA-treated rats. Finally, we analyzed the effects of ambroxol, a Nav1.8-preferring blocker on the electrophysiological properties of Nav1.8 currents and on the mechanical sensitivity and inflammation of the hind paw in CFA-treated rats. Results Our findings revealed that Nav1.8 is up-regulated in NF200-positive large sensory neurons and is subsequently anterogradely transported from the DRG cell bodies along the axons toward the periphery after CFA-induced inflammation. We also demonstrated that both total INa and Nav1.8 peak current densities are enhanced in inflamed large myelinated Aβ-fiber neurons. Persistent inflammation leading to nociception also induced time-dependent changes in Aβ-fiber neuron excitability by shifting the voltage-dependent activation of Nav1.8 in the hyperpolarizing direction, thus decreasing the current threshold for triggering action potentials. Finally, we found that ambroxol significantly reduces the potentiation of Nav1.8 currents in Aβ-fiber neurons observed following intraplantar CFA injection and

  20. Salivary cytokine levels in early gingival inflammation

    DEFF Research Database (Denmark)

    Belstrøm, Daniel; Damgaard, Christian; Könönen, Eija

    2017-01-01

    Salivary protein levels have been studied in periodontitis. However, there is lack of information on salivary cytokine levels in early gingival inflammation. The aim of this study was to determine salivary levels of vascular endothelial growth factor (VEGF), interleukin (IL)-8, monocyte chemoattr......Salivary protein levels have been studied in periodontitis. However, there is lack of information on salivary cytokine levels in early gingival inflammation. The aim of this study was to determine salivary levels of vascular endothelial growth factor (VEGF), interleukin (IL)-8, monocyte...... chemoattractant protein (MCP)-1, IL-1β, and IL-1 receptor antagonist (IL-1Ra) in gingival inflammation. Twenty-eight systemically and orally healthy nonsmokers abstained from oral hygiene protocols for 10 days. After that, self-performed cleaning was resumed for 14 days. Plaque and gingival indexes were measured...... levels decreased and remained low during development and resolution of experimental gingivitis. Initial inflammation in gingival tissues is associated with a decrease in inflammatory cytokines in saliva. Further studies are needed to evaluate if inflammatory cytokines bind to their functional receptors...

  1. Rapid non-genomic effects of aldosterone on rodent vascular function

    DEFF Research Database (Denmark)

    Uhrenholt, T R; Schjerning, J; Rasmussen, L E

    2004-01-01

    The main role of aldosterone is to maintain body sodium homeostasis by promoting salt reabsorption in the collecting ducts of the kidney. In the cardiovascular system, aldosterone may be harmful in a number of disease states by inducing fibrosis and vascular dysfunction. The present review...

  2. Impaired vascular function during short-term poor glycaemic control in Type 1 diabetic patients

    DEFF Research Database (Denmark)

    Sørensen, V R; Mathiesen, E R; Clausen, P

    2005-01-01

    -dependent dilation) and to nitroglycerin (endothelium-independent dilation). Plasma concentration of von Willebrand factor antigen, adhesion molecules, vascular endothelial growth factor, homocystein and cholesterol were also measured. RESULTS: The median blood glucose levels in the 48 h before the examinations were...

  3. Long-term consequences of developmental vascular defects on retinal vessel homeostasis and function in a mouse model of Norrie disease.

    Directory of Open Access Journals (Sweden)

    Susanne C Beck

    Full Text Available Loss of Norrin signalling due to mutations in the Norrie disease pseudoglioma gene causes severe vascular defects in the retina, leading to visual impairment and ultimately blindness. While the emphasis of experimental work so far was on the developmental period, we focus here on disease mechanisms that induce progression into severe adult disease. The goal of this study was the comprehensive analysis of the long-term effects of the absence of Norrin on vascular homeostasis and retinal function. In a mouse model of Norrie disease retinal vascular morphology and integrity were studied by means of in vivo angiography; the vascular constituents were assessed in detailed histological analyses using quantitative retinal morphometry. Finally, electroretinographic analyses were performed to assess the retinal function in adult Norrin deficient animals. We could show that the primary developmental defects not only persisted but developed into further vascular abnormalities and microangiopathies. In particular, the overall vessel homeostasis, the vascular integrity, and also the cellular constituents of the vascular wall were affected in the adult Norrin deficient retina. Moreover, functional analyses indicated to persistent hypoxia in the neural retina which was suggested as one of the major driving forces of disease progression. In summary, our data provide evidence that the key to adult Norrie disease are ongoing vascular modifications, driven by the persistent hypoxic conditions, which are ineffective to compensate for the primary Norrin-dependent defects.

  4. Dark chocolate consumption improves leukocyte adhesion factors and vascular function in overweight men

    NARCIS (Netherlands)

    Esser, D.; Mars, M.; Oosterink, E.; Stalmach, A.; Müller, M.R.; Afman, L.A.

    2014-01-01

    Flavanol-enriched chocolate consumption increases endothelium-dependent vasodilation. Most research so far has focused on flow-mediated dilation (FMD) only; the effects on other factors relevant to endothelial health, such as inflammation and leukocyte adhesion, have hardly been addressed. We

  5. Chronic Stress Improves NO- and Ca2+ Flux-Dependent Vascular Function: A Pharmacological Study.

    Science.gov (United States)

    Bruder-Nascimento, Thiago; Campos, Dijon Henrique Salome

    2015-01-23

    Background: Stress is associated with cardiovascular diseases. Objective: This study aimed at assessing whether chronic stress induces vascular alterations, and whether these modulations are nitric oxide (NO) and Ca2+ dependent. Methods: Wistar rats, 30 days of age, were separated into 2 groups: control (C) and Stress (St). Chronic stress consisted of immobilization for 1 hour/day, 5 days/week, 15 weeks. Systolic blood pressure was assessed. Vascular studies on aortic rings were performed. Concentration-effect curves were built for noradrenaline, in the presence of L-NAME or prazosin, acetylcholine, sodium nitroprusside and KCl. In addition, Ca2+ flux was also evaluated. Results: Chronic stress induced hypertension, decreased the vascular response to KCl and to noradrenaline, and increased the vascular response to acetylcholine. L-NAME blunted the difference observed in noradrenaline curves. Furthermore, contractile response to Ca2+ was decreased in the aorta of stressed rats. Conclusion: Our data suggest that the vascular response to chronic stress is an adaptation to its deleterious effects, such as hypertension. In addition, this adaptation is NO- and Ca2+-dependent. These data help to clarify the contribution of stress to cardiovascular abnormalities. However, further studies are necessary to better elucidate the mechanisms involved in the cardiovascular dysfunction associated with stressors. (Arq Bras Cardiol. 2014; [online].ahead print, PP.0-0)Fundamento: Estresse está associado com complicações cardiovasculares. Objetivos: O objetivo do presente estudo foi avaliar se o estresse crônico induz alterações vasculares, e se essas alterações são dependentes de óxido nítrico (NO) e Ca2+. Métodos: Ratos machos Wistar com 30 dias de idade foram separados em 2 grupos: controle (C) e Estresse (St). Utilizou-se estresse crônico de imobilização por 1 hora/dia, 5 dias/semana, 15 semanas. Pressão arterial sistólica foi avaliada. A função vascular foi

  6. Sertoli Cells Modulate Testicular Vascular Network Development, Structure, and Function to Influence Circulating Testosterone Concentrations in Adult Male Mice.

    Science.gov (United States)

    Rebourcet, Diane; Wu, Junxi; Cruickshanks, Lyndsey; Smith, Sarah E; Milne, Laura; Fernando, Anuruddika; Wallace, Robert J; Gray, Calum D; Hadoke, Patrick W F; Mitchell, Rod T; O'Shaughnessy, Peter J; Smith, Lee B

    2016-06-01

    The testicular vasculature forms a complex network, providing oxygenation, micronutrients, and waste clearance from the testis. The vasculature is also instrumental to testis function because it is both the route by which gonadotropins are delivered to the testis and by which T is transported away to target organs. Whether Sertoli cells play a role in regulating the testicular vasculature in postnatal life has never been unequivocally demonstrated. In this study we used models of acute Sertoli cell ablation and acute germ cell ablation to address whether Sertoli cells actively influence vascular structure and function in the adult testis. Our findings suggest that Sertoli cells play a key role in supporting the structure of the testicular vasculature. Ablating Sertoli cells (and germ cells) or germ cells alone results in a similar reduction in testis size, yet only the specific loss of Sertoli cells leads to a reduction in total intratesticular vascular volume, the number of vascular branches, and the numbers of small microvessels; loss of germ cells alone has no effect on the testicular vasculature. These perturbations to the testicular vasculature leads to a reduction in fluid exchange between the vasculature and testicular interstitium, which reduces gonadotropin-stimulated circulating T concentrations, indicative of reduced Leydig cell stimulation and/or reduced secretion of T into the vasculature. These findings describe a new paradigm by which the transport of hormones and other factors into and out of the testis may be influenced by Sertoli cells and highlights these cells as potential targets for enhancing this endocrine relationship.

  7. Vascular endothelial function and oxidative stress are related to dietary niacin intake among healthy middle-aged and older adults.

    Science.gov (United States)

    Kaplon, Rachelle E; Gano, Lindsey B; Seals, Douglas R

    2014-01-15

    We tested the hypothesis that vascular endothelial function and oxidative stress are related to dietary niacin intake among healthy middle-aged and older adults. In 127 men and women aged 48-77 yr, brachial artery flow-mediated dilation (FMD) was positively related to dietary niacin intake [%change (Δ): r = 0.20, P niacin intake (≥ 22 mg/day, NHANES III), FMD was 25% greater than in subjects with below-average intake (P niacin intake (above vs. below average) was an independent predictor of FMD (%Δ: β = 1.8; mmΔ: β = 0.05, both P niacin intake (r = -0.23, P niacin intake (48 ± 2 vs. 57 ± 2 mg/dl, P niacin intake (P 0.05, n = 20). In endothelial cells sampled from the brachial artery of a subgroup, dietary niacin intake was inversely related to nitrotyrosine, a marker of peroxynitrite-mediated oxidative damage (r = -0.30, P niacin intake [nitrotyrosine: 0.39 ± 0.05 vs. 0.56 ± 0.07; NADPH oxidase: 0.38 ± 0.05 vs. 0.53 ± 0.05 (ratio to human umbilical vein endothelial cell control), both P niacin intake is associated with greater vascular endothelial function related to lower systemic and vascular oxidative stress among healthy middle-aged and older adults.

  8. Effect of adjuvant argatroban therapy on neurological function, endothelial injury and inflammation state in patient with acute cerebral infarction

    Directory of Open Access Journals (Sweden)

    Nan Che

    2016-08-01

    Full Text Available Objective: To analyze the effect of adjuvant argatroban therapy on neurological function, endothelial injury and inflammation state in patient with acute cerebral infarction. Methods: A total of 118 patients with acute cerebral infarction were divided into observation group and control group according to the random number table, control group received conventional treatment, observation group received argatroban + conventional treatment, and then differences in TCD cerebral blood flow, serum neurological function, endothelial injury and inflammatory marker levels were compared between two groups after treatment. Results: TCD MCA and ACA values of observation group after treatment were higher than those of control group (P<0.05; serum neurological function indexes copeptin, NT-proBNP, PAO and S-100B levels of observation group after treatment were lower than those of control group, endothelial injury index ET-1 level was lower than that of control group, NO and CGRP levels were higher than those of control group, and inflammatory markers hs-CRP, TNF-毩, IL-6, MMP-9 and Lp-PLA2 levels were lower than those of control group (P<0.05. Conclusions: Adjuvant argatroban therapy can optimize the overall condition in patients with acute cerebral infarction, and plays a positive role in improving the neurological function, reducing endothelial injury and inflammation state, etc.

  9. Multiparametric Functional MRI: Non-Invasive Imaging of Inflammation and Edema Formation after Kidney Transplantation in Mice.

    Directory of Open Access Journals (Sweden)

    Katja Hueper

    Full Text Available Kidney transplantation (ktx in mice is used to learn about rejection and to develop new treatment strategies. Past studies have mainly been based on histological or molecular biological methods. Imaging techniques to monitor allograft pathology have rarely been used.Here we investigated mice after isogenic and allogenic ktx over time with functional MRI with diffusion-weighted imaging (DWI and mapping of T2-relaxation time (T2-mapping to assess graft inflammation and edema formation. To characterize graft pathology, we used PAS-staining, counted CD3-positive T-lymphocytes, analyzed leukocytes by means flow cytometry.DWI revealed progressive restriction of diffusion of water molecules in allogenic kidney grafts. This was paralleled by enhanced infiltration of the kidney by inflammatory cells. Changes in tissue diffusion were not seen following isogenic ktx. T2-times in renal cortex were increased after both isogenic and allogenic transplantation, consistent with tissue edema due to ischemic injury following prolonged cold ischemia time of 60 minutes. Lack of T2 increase in the inner stripe of the inner medulla in allogenic kidney grafts matched loss of tubular autofluorescence and may result from rejection-driven reductions in tubular water content due to tubular dysfunction and renal functional impairment.Functional MRI is a valuable non-invasive technique for monitoring inflammation, tissue edema and tubular function. It permits on to differentiate between acute rejection and ischemic renal injury in a mouse model of ktx.

  10. Infected erythrocyte-derived extracellular vesicles alter vascular function via regulatory Ago2-miRNA complexes in malaria.

    Science.gov (United States)

    Mantel, Pierre-Yves; Hjelmqvist, Daisy; Walch, Michael; Kharoubi-Hess, Solange; Nilsson, Sandra; Ravel, Deepali; Ribeiro, Marina; Grüring, Christof; Ma, Siyuan; Padmanabhan, Prasad; Trachtenberg, Alexander; Ankarklev, Johan; Brancucci, Nicolas M; Huttenhower, Curtis; Duraisingh, Manoj T; Ghiran, Ionita; Kuo, Winston P; Filgueira, Luis; Martinelli, Roberta; Marti, Matthias

    2016-10-10

    Malaria remains one of the greatest public health challenges worldwide, particularly in sub-Saharan Africa. The clinical outcome of individuals infected with Plasmodium falciparum parasites depends on many factors including host systemic inflammatory responses, parasite sequestration in tissues and vascular dysfunction. Production of pro-inflammatory cytokines and chemokines promotes endothelial activation as well as recruitment and infiltration of inflammatory cells, which in turn triggers further endothelial cell activation and parasite sequestration. Inflammatory responses are triggered in part by bioactive parasite products such as hemozoin and infected red blood cell-derived extracellular vesicles (iRBC-derived EVs). Here we demonstrate that such EVs contain functional miRNA-Argonaute 2 complexes that are derived from the host RBC. Moreover, we show that EVs are efficiently internalized by endothelial cells, where the miRNA-Argonaute 2 complexes modulate target gene expression and barrier properties. Altogether, these findings provide a mechanistic link between EVs and vascular dysfunction during malaria infection.

  11. Chronic consumption of flavanol-rich cocoa improves endothelial function and decreases vascular cell adhesion molecule in hypercholesterolemic postmenopausal women.

    Science.gov (United States)

    Wang-Polagruto, Janice F; Villablanca, Amparo C; Polagruto, John A; Lee, Luke; Holt, Roberta R; Schrader, Heather R; Ensunsa, Jodi L; Steinberg, Francene M; Schmitz, Harold H; Keen, Carl L

    2006-01-01

    Endothelial dysfunction characterizes many disease states including subclinical atherosclerosis. The consumption of flavanol-rich cocoa and cocoa-based products has been shown to improve endothelial function in both compromised and otherwise normal, healthy individuals when administered either acutely or over a period of several days, or weeks. Women experience increased risk for cardiovascular disease after menopause, which can be associated with endothelial dysfunction. Whether a flavanol-rich cocoa-based product can improve endothelial function in hypercholesterolemic postmenopausal women is not known. The purpose of the present study was to determine whether chronic dietary administration of flavanol-rich cocoa improves endothelial function and markers of cardiovascular health in hypercholesterolemic postmenopausal women. Thirty-two postmenopausal hypercholesterolemic women were randomly assigned to consume a high-flavanol cocoa beverage (high cocoa flavanols (CF)--446 mg of total flavanols), or a low-flavanol cocoa beverage (low CF--43 mg of total flavanols) for 6 weeks in a double-blind study (n=16 per group). Endothelial function was determined by brachial artery-reactive hyperemia. Plasma was analyzed for lipids (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol), hormones (follicle-stimulating hormone), total nitrate/nitrite, activation of cellular adhesion markers (vascular cell adhesion molecule 1, intercellular adhesion molecule 1, E-Selectin, P-Selectin), and platelet function and reactivity. Changes in these plasma markers were then correlated to brachial reactivity. Brachial artery hyperemic blood flow increased significantly by 76% (Pflavanol-rich cocoa consumption in hypercholesterolemic postmenopausal women. In addition, our results suggest that reductions in plasma soluble vascular cell adhesion molecule-1 after chronic consumption of a flavanol-rich cocoa may be mechanistically linked to improved

  12. Involvement of Semicarbazide-Sensitive Amine Oxidase-Mediated Deamination in Lipopolysaccharide-Induced Pulmonary Inflammation

    OpenAIRE

    Yu, Peter H.; Lu, Li-Xin; Fan, Hui; Kazachkov, Mychaylo; Jiang, Zhong-Jian; Jalkanen, Sirpa; Stolen, Craig

    2006-01-01

    Semicarbazide-sensitive amine oxidase (SSAO) resides on the vascular endothelium and smooth muscle cell surface and is capable of deaminating short chain aliphatic amines and producing toxic aldehydes and hydrogen peroxide. The enzyme, also known as a vascular adhesion protein-1, is involved in the inflammation process. This intriguing protein with dual functions is increased in the serum of diabetic and heart failure patients. In the present study we assessed the involvement of SSAO in a lip...

  13. Toll-like receptors and damage-associated molecular patterns: novel links between inflammation and hypertension

    OpenAIRE

    McCarthy, Cameron G.; Goulopoulou, Styliani; Wenceslau, Camilla F.; Spitler, Kathryn; Matsumoto, Takayuki; Webb, R. Clinton

    2013-01-01

    Low-grade systemic inflammation is a common manifestation of hypertension; however, the exact mechanisms that initiate this pathophysiological response, thereby contributing to further increases in blood pressure, are not well understood. Aberrant vascular inflammation and reactivity via activation of the innate immune system may be the first step in the pathogenesis of hypertension. One of the functions of the innate immune system is to recognize and respond to danger. Danger signals can ari...

  14. Physical activity measured by accelerometry and its associations with cardiac structure and vascular function in young and middle-aged adults

    DEFF Research Database (Denmark)

    Andersson, Charlotte; Lyass, Asya; Larson, Martin G

    2015-01-01

    BACKGROUND: Physical activity is associated with several health benefits, including lower cardiovascular disease risk. The independent influence of physical activity on cardiac and vascular function in the community, however, has been sparsely investigated. MEASURES AND RESULTS: We related...

  15. Maternal endothelial function and vascular stiffness after HELLP syndrome: a case-control study.

    Science.gov (United States)

    Orabona, R; Sciatti, E; Vizzardi, E; Bonadei, I; Prefumo, F; Valcamonico, A; Metra, M; Frusca, T

    2017-11-01

    To assess endothelial function and arterial stiffness in women with a previous pregnancy complicated by pre-eclampsia (PE) with hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome, and to compare these findings to those in women with previous PE but no HELLP and to those in controls with previous uncomplicated pregnancy, in order to investigate the influence of HELLP syndrome on subsequent cardiovascular impairment. In this prospective single-center case-control study, we performed peripheral arterial tonometry (PAT) (using the EndoPAT method) and pulse-wave velocity (PWV) assessment in 109 women who had had a singleton pregnancy complicated by PE with (n = 49) or without (n = 60) HELLP syndrome, as well as in 60 controls with previous uncomplicated pregnancy, between 6 months and 4 years after delivery. The following EndoPAT and PWV indices were compared between groups: reactive hyperemia index (RHI), as an indication of endothelial function, and peripheral and aortic heart-rate-corrected augmentation indices (AIx) standardized for a heart rate of 75 bpm (AIx@75) and carotid-femoral pulse-wave velocity (cfPWV), as indications of arterial stiffness. PAT and arterial stiffness indices were significantly different between PE cases, with or without previous HELLP, and controls, except for carotid-femoral PWV. There were no significant differences among PE groups: women who had experienced HELLP and those with a history of PE without HELLP showed similar rates of RHI ≤ 1.67 (28.6% vs 18.3%, P = 0.254) and RHI ≤ 2.00 (61.2% vs 41.7%, P = 0.055), peripheral AIx@75 ≥ 17% (38.8% vs 30.0%, P = 0.417), aortic AIx@75 ≥ 35% (29.2% vs 20.0%, P = 0.461) and cfPWV × 0.8 > 9.6 m/s, which occurred in only three women, all in the group without previous HELLP (0% vs 5.0%, P = 0.251). On multivariate regression analysis, HELLP syndrome, intrauterine growth restriction (IUGR) and early-onset PE

  16. Effects of Olive Oil on Markers of Inflammation and Endothelial Function-A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Schwingshackl, Lukas; Christoph, Marina; Hoffmann, Georg

    2015-09-11

    The aim of the present systematic review was to synthesize data from randomized controlled trials investigating the effects of olive oil on markers of inflammation or endothelial function. Literature search in electronic databases Cochrane Trial Register, EMBASE, and MEDLINE was performed. Thirty studies enrolling 3106 participants fulfilled the selection criteria. Pooled effects of different interventions were assessed as mean difference using a random effects model. Olive oil interventions (with daily consumption ranging approximately between 1 mg and 50 mg) resulted in a significantly more pronounced decrease in C-reactive protein (mean difference: -0.64 mg/L, (95% confidence interval (CI) -0.96 to -0.31), p oil interventions (mean difference: 0.76% (95% CI 0.27 to 1.24), p oil might exert beneficial effects on endothelial function as well as markers of inflammation and endothelial function, thus representing a key ingredient contributing to the cardiovascular-protective effects of a Mediterranean diet. However, due to the heterogeneous study designs (e.g., olive oil given as a supplement or as part of dietary pattern, variations in control diets), a conservative interpretation of the results is necessary.

  17. Effects of catalpol on mitochondrial function and working memory in mice after lipopolysaccharide-induced acute systemic inflammation.

    Science.gov (United States)

    Zhang, Aihong; Hao, Shuang; Bi, Jing; Bao, Yongming; Zhang, Xiuli; An, Lijia; Jiang, Bo

    2009-09-01

    The aim of this study was to investigate whether catalpol could facilitate recovery from lipopolysaccharide (LPS)-induced cognitive deficits and protect brain mitochondrial function from LPS-induced acute systemic inflammation. In the study, except control group, mice were challenged with a single dose of LPS (100 microg/mouse, i.p.) to mimic an acute peripheral infection. The results showed that LPS enhanced nuclear factor kappa B (NF-kappaB) activation and induced a loss in mitochondrial integrity as shown by a significant decrease in membrane potential and increase in mitochondrial permeability transition pore opening. Pretreatment with catalpol (10 mg/kg d, i.p.) for 10d before injection of LPS reversed the memory deficits induced by LPS, protected brain mitochondrial function, and attenuated LPS-induced NF-kappaB activation. Taken together, these data indicate that catalpol may possess therapeutic potential against LPS-induced acute systemic inflammation by attenuating NF-kappaB activation and protecting mitochondrial function in cerebral cortex and hippocampus.

  18. Vascular status and physical functioning: the association between vascular status and physical functioning in middle-aged and elderly men: a cross-sectional study

    NARCIS (Netherlands)

    Prof. Dr. Marieke J. Schuurmans; Yvonne van der Schouw; Ilse Arts; Diederick Grobbee

    2010-01-01

    Living independently is an important component of quality of life. Cardiovascular diseases are prominent among the chronic conditions that predispose elderly people to functional limitations and disability, which impair quality of life. Insight into factors that play a role in the development