Reduced proliferation of endothelial colony-forming cells in unprovoked venous thromboembolic disease as a consequence of endothelial dysfunction

Science.gov (United States)

Hernandez-Lopez, Rubicel; Chavez-Gonzalez, Antonieta; Torres-Barrera, Patricia; Moreno-Lorenzana, Dafne; Lopez-DiazGuerrero, Norma; Santiago-German, David; Isordia-Salas, Irma; Smadja, David; C. Yoder, Mervin; Majluf-Cruz, Abraham

2017-01-01

Background Venous thromboembolic disease (VTD) is a public health problem. We recently reported that endothelial colony-forming cells (ECFCs) derived from endothelial cells (EC) (ECFC-ECs) from patients with VTD have a dysfunctional state. For this study, we proposed that a dysfunctional status of these cells generates a reduction of its proliferative ability, which is also associated with senescence and reactive oxygen species (ROS). Methods and results Human mononuclear cells (MNCs) were obtained from peripheral blood from 40 healthy human volunteers (controls) and 50 patients with VTD matched by age (20−50 years) and sex to obtain ECFCs. We assayed their proliferative ability with plasma of patients and controls and supernatants of cultures from ECFC-ECs, senescence-associated β-galactosidase (SA-β-gal), ROS, and expression of ephrin-B2/Eph-B4 receptor. Compared with cells from controls, cells from VTD patients showed an 8-fold increase of ECFCs that emerged 1 week earlier, reduced proliferation at long term (39%) and, in passages 4 and 10, a highly senescent rate (30±1.05% vs. 91.3±15.07%, respectively) with an increase of ROS and impaired expression of ephrin-B2/Eph-4 genes. Proliferation potential of cells from VTD patients was reduced in endothelial medium [1.4±0.22 doubling population (DP)], control plasma (1.18±0.31 DP), or plasma from VTD patients (1.65±0.27 DP). Conclusions As compared with controls, ECFC-ECs from individuals with VTD have higher oxidative stress, proliferation stress, cellular senescence, and low proliferative potential. These findings suggest that patients with a history of VTD are ECFC-ECs dysfunctional that could be associated to permanent risk for new thrombotic events. PMID:28910333

Wine and endothelial function.

Science.gov (United States)

Caimi, G; Carollo, C; Lo Presti, R

2003-01-01

In recent years many studies have focused on the well-known relationship between wine consumption and cardiovascular risk. Wine exerts its protective effects through various changes in lipoprotein profile, coagulation and fibrinolytic cascades, platelet aggregation, oxidative mechanisms and endothelial function. The last has earned more attention for its implications in atherogenesis. Endothelium regulates vascular tone by a delicate balancing among vasorelaxing (nitric oxide [NO]) and vasoconstrincting (endothelins) factors produced by endothelium in response to various stimuli. In rat models, wine and other grape derivatives exerted an endothelium-dependent vasorelaxing capacity especially associated with the NO-stimulating activity of their polyphenol components. In experimental conditions, reservatrol (a stilbene polyphenol) protected hearts and kidneys from ischemia-reperfusion injury through antioxidant activity and upregulation of NO production. Wine polyphenols are also able to induce the expression of genes involved in the NO pathway within the arterial wall. The effects of wine on endothelial function in humans are not yet clearly understood. A favorable action of red wine or dealcoholized wine extract or purple grape juice on endothelial function has been observed by several authors, but discrimination between ethanol and polyphenol effects is controversial. It is, however likely that regular and prolonged moderate wine drinking positively affects endothelial function. The beneficial effects of wine on cardiovascular health are greater if wine is associated with a healthy diet. The most recent nutritional and epidemiologic studies show that the ideal diet closely resembles the Mediterranean diet.

The endothelial αENaC contributes to vascular endothelial function in vivo

DEFF Research Database (Denmark)

Tarjus, Antoine; Maase, Martina; Jeggle, Pia

2017-01-01

The Epithelial Sodium Channel (ENaC) is a key player in renal sodium homeostasis. The expression of α β γ ENaC subunits has also been described in the endothelium and vascular smooth muscle, suggesting a role in vascular function. We recently demonstrated that endothelial ENaC is involved in aldo......-mediated dilation. Our data suggest that endothelial αENaC contributes to vascular endothelial function in vivo....

Circulating endothelial cells in patients with venous thromboembolism and myeloproliferative neoplasms.

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Cláudia Torres

Full Text Available BACKGROUND: Circulating endothelial cells (CEC may be a biomarker of vascular injury and pro-thrombotic tendency, while circulating endothelial progenitor cells (CEP may be an indicator for angiogenesis and vascular remodelling. However, there is not a universally accepted standardized protocol to identify and quantify these cells and its clinical relevancy remains to be established. OBJECTIVES: To quantify CEC and CEP in patients with venous thromboembolism (VTE and with myeloproliferative neoplasms (MPN, to characterize the CEC for the expression of activation (CD54, CD62E and procoagulant (CD142 markers and to investigate whether they correlate with other clinical and laboratory data. PATIENTS AND METHODS: Sixteen patients with VTE, 17 patients with MPN and 20 healthy individuals were studied. The CEC and CEP were quantified and characterized in the blood using flow cytometry, and the demographic, clinical and laboratory data were obtained from hospital records. RESULTS: We found the CEC counts were higher in both patient groups as compared to controls, whereas increased numbers of CEP were found only in patients with MPN. In addition, all disease groups had higher numbers of CD62E+ CEC as compared to controls, whereas only patients with VTE had increased numbers of CD142+ and CD54+ CEC. Moreover, the numbers of total and CD62+ CEC correlated positively with the white blood cells (WBC counts in both groups of patients, while the numbers of CEP correlated positively with the WBC counts only in patients with MPN. In addition, in patients with VTE a positive correlation was found between the numbers of CD54+ CEC and the antithrombin levels, as well as between the CD142+ CEC counts and the number of thrombotic events. CONCLUSIONS: Our study suggests that CEC counts may reveal endothelial injury in patients with VTE and MPN and that CEC may express different activation-related phenotypes depending on the disease status.

Low Molecular Weight Heparin Improves Endothelial Function in Pregnant Women at High Risk of Preeclampsia.

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McLaughlin, Kelsey; Baczyk, Dora; Potts, Audrey; Hladunewich, Michelle; Parker, John D; Kingdom, John C P

2017-01-01

Low molecular weight heparin (LMWH) has been investigated for the prevention of severe preeclampsia, although the mechanisms of action are unknown. The objective of this study was to investigate the cardiovascular effects of LMWH in pregnant women at high risk of preeclampsia. Pregnant women at high risk of preeclampsia (n=25) and low-risk pregnant controls (n=20) at 22 to 26 weeks' gestation underwent baseline cardiovascular assessments. High-risk women were then randomized to LMWH or saline placebo (30 mg IV bolus and 1 mg/kg subcutaneous dose). Cardiovascular function was assessed 1 and 3 hours post randomization. The in vitro endothelial effects of patient serum and exogenous LMWH on human umbilical venous endothelial cells were determined. High-risk women demonstrated a reduced cardiac output, high resistance hemodynamic profile with impaired radial artery flow-mediated dilation compared with controls. LMWH increased flow-mediated dilation in high-risk women 3 hours after randomization compared with baseline and increased plasma levels of placental growth factor, soluble fms-like tyrosine kinase-1, and myeloperoxidase. Serum from high-risk women impaired endothelial cell angiogenesis and increased PlGF-1 and PlGF-2 transcription compared with serum from low-risk controls. Coexposure of high-risk serum with LMWH improved the in vitro angiogenic response such that it was equivalent to that of low-risk serum and promoted placental growth factor secretion. LMWH improves maternal endothelial function in pregnant women at high risk of developing preeclampsia, possibly mediated through increased placental growth factor bioavailability. © 2016 American Heart Association, Inc.

Percutaneous bioprosthetic venous valve: a long-term study in sheep.

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Pavcnik, Dusan; Uchida, Barry T; Timmermans, Hans A; Corless, Christopher L; O'Hara, Michael; Toyota, Naoyuki; Moneta, Gregory L; Keller, Frederick S; Rösch, Josef

2002-03-01

A long-term evaluation of a new percutaneously placed bioprosthetic, bicuspid venous valve (BVV) consisting of a square stent and small intestinal submucosa (SIS) covering was performed in 12 sheep. Of 26 BVVs placed into the jugular veins, 25 exhibited good valve function on immediate venography and 22 on venograms obtained before the sheep were killed. Gross and histologic examination results demonstrated incorporation of remodeled and endothelialized SIS BVVs into the vein wall. Slight to moderate leaflet thickening was found mostly at their bases. Percutaneously placed SIS BVV is a promising one-way, competent valve that resists venous back-pressure while allowing forward flow.

Endovascular treatment of chronic cerebro spinal venous insufficiency in patients with multiple sclerosis modifies circulating markers of endothelial dysfunction and coagulation activation: a prospective study.

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Napolitano, Mariasanta; Bruno, Aldo; Mastrangelo, Diego; De Vizia, Marcella; Bernardo, Benedetto; Rosa, Buonagura; De Lucia, Domenico

2014-10-01

We performed a monocentric observational prospective study to evaluate coagulation activation and endothelial dysfunction parameters in patients with multiple sclerosis undergoing endovascular treatment for cerebro-spinal-venous insufficiency. Between February 2011 and July 2012, 144 endovascular procedures in 110 patients with multiple sclerosis and chronical cerebro-spinal venous insufficiency were performed and they were prospectively analyzed. Each patient was included in the study according to previously published criteria, assessed by the investigators before enrollment. Endothelial dysfunction and coagulation activation parameters were determined before the procedure and during follow-up at 1, 3, 6, 9, 12, 15 and 18 months after treatment, respectively. After the endovascular procedure, patients were treated with standard therapies, with the addition of mesoglycan. Fifty-five percent of patients experienced a favorable outcome of multiple sclerosis within 1 month after treatment, 25% regressed in the following 3 months, 24.9% did not experience any benefit. In only 0.1% patients, acute recurrence was observed and it was treated with high-dose immunosuppressive therapy. No major complications were observed. Coagulation activation and endothelial dysfunction parameters were shown to be reduced at 1 month and stable up to 12-month follow-up, and they were furthermore associated with a good clinical outcome. Endovascular procedures performed by a qualified staff are well tolerated; they can be associated with other currently adopted treatments. Correlations between inflammation, coagulation activation and neurodegenerative disorders are here supported by the observed variations in plasma levels of markers of coagulation activation and endothelial dysfunction.

Insomnia and endothelial function - the HUNT 3 fitness study.

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Linn B Strand

Full Text Available BACKGROUND: Insomnia is associated with increased risk of coronary heart disease (CHD, but the underlying mechanisms are not understood. To our knowledge, no previous studies have examined insomnia in relation to endothelial function, an indicator of preclinical atherosclerosis. Our aim was to assess the association of insomnia with endothelial function in a large population based study of healthy individuals. METHODS: A total of 4 739 participants free from known cardiovascular or pulmonary diseases, cancer, and sarcoidosis, and who were not using antihypertensive medication were included in the study. They reported how often they had experienced difficulties falling asleep at night, repeated awakenings during the night, early awakenings without being able to go back to sleep, and daytime sleepiness. Endothelial function was measured by flow mediated dilation (FMD derived from the brachial artery. RESULTS: We found no consistent association between the insomnia symptoms and endothelial function in multiadjusted models, but individual insomnia symptoms may be related to endothelial function. Among women who reported early awakenings, endothelial function may be lower than in women without this symptom (p = 0.03. CONCLUSIONS: This study provided no evidence that endothelial function, an early indicator of atherosclerosis, is an important linking factor between insomnia and CHD. Further studies are needed to explore the complex interrelation between sleep and cardiovascular pathology.

Apelin is a novel angiogenic factor in retinal endothelial cells

International Nuclear Information System (INIS)

Kasai, Atsushi; Shintani, Norihito; Oda, Maki; Kakuda, Michiya; Hashimoto, Hitoshi; Matsuda, Toshio; Hinuma, Shuji; Baba, Akemichi

2004-01-01

There has been much focus recently on the possible functions of apelin, an endogenous ligand for the orphan G-protein-coupled receptor APJ, in cardiovascular and central nervous systems. We report a new function of apelin as a novel angiogenic factor in retinal endothelial cells. The retinal endothelial cell line RF/6A highly expressed both apelin and APJ transcripts, while human umbilical venous endothelial cells (HUVECs) only expressed apelin mRNA. In accordance with these observations, apelin at concentrations of 1 pM-1 μM significantly enhanced migration, proliferation, and capillary-like tube formation of RF/6A cells, but not those of HUVECs, whereas VEGF stimulates those parameters of both cell types. In vivo Matrigel plug assay for angiogenesis, the inclusion of 1 nM apelin in the Matrigel resulted in clear capillary-like formations with an increase of hemoglobin content in the plug. This is the first report showing that apelin is an angiogenic factor in retinal endothelial cells

Weight loss improves biomarkers endothelial function and systemic ...

African Journals Online (AJOL)

Background: Although postmenopausal associated disorders are important public health problems worldwide, to date limited studies evaluated the endothelial function and systemic inflammation response to weight loss in obese postmenopausal women. Objective: This study was done to evaluate the endothelial function ...

Sustained apnea induces endothelial activation.

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Eichhorn, Lars; Dolscheid-Pommerich, Ramona; Erdfelder, Felix; Ayub, Muhammad Ajmal; Schmitz, Theresa; Werner, Nikos; Jansen, Felix

2017-09-01

Apnea diving has gained worldwide popularity, even though the pathophysiological consequences of this challenging sport on the human body are poorly investigated and understood. This study aims to assess the influence of sustained apnea in healthy volunteers on circulating microparticles (MPs) and microRNAs (miRs), which are established biomarkers reflecting vascular function. Short intermittent hypoxia due to voluntary breath-holding affects circulating levels of endothelial cell-derived MPs (EMPs) and endothelial cell-derived miRs. Under dry laboratory conditions, 10 trained apneic divers performed maximal breath-hold. Venous blood samples were taken, once before and at 4 defined points in time after apnea. Samples were analyzed for circulating EMPs and endothelial miRs. Average apnea time was 329 seconds (±103), and SpO 2 at the end of apnea was 79% (±12). Apnea was associated with a time-dependent increase of circulating endothelial cell-derived EMPs and endothelial miRs. Levels of circulating EMPs in the bloodstream reached a peak 4 hours after the apnea period and returned to baseline levels after 24 hours. Circulating miR-126 levels were elevated at all time points after a single voluntary maximal apnea, whereas miR-26 levels were elevated significantly only after 30 minutes and 4 hours. Also miR-21 and miR-92 levels increased, but did not reach the level of significance. Even a single maximal breath-hold induces acute endothelial activation and should be performed with great caution by subjects with preexisting vascular diseases. Voluntary apnea might be used as a model to simulate changes in endothelial function caused by hypoxia in humans. © 2017 Wiley Periodicals, Inc.

Resveratrol: A Multifunctional Compound Improving Endothelial Function

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Li, Huige; F?rstermann, Ulrich

2009-01-01

The red wine polyphenol resveratrol boosts endothelium-dependent and -independent vasorelaxations. The improvement of endothelial function by resveratrol is largely attributable to nitric oxide (NO) derived from endothelial NO synthase (eNOS). By stimulating eNOS expression, eNOS phosphorylation and eNOS deacetylation, resveratrol enhances endothelial NO production. By upregulating antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) and suppressing the expression a...

Venous muscle pump function during pregnancy. Assessment by ambulatory strain-gauge plethysmography

DEFF Research Database (Denmark)

Struckmann, J R; Meiland, H; Bagi, P

1990-01-01

The venous muscle pump function was quantitatively assessed through pregnancy weeks 16, 30, 38 and 3 months (week 53) following delivery, in 24 pregnant women who completed a normal pregnancy. A statistically significant increase was found in the mean venous reflux (P less than 0.01), which was r...... primarily by mechanical obstruction, or hormonal influence other than that of estradiol, estriol or progesterone. 17% (4.7-37%) of the women with a normal pregnancy developed a pathological venous muscle pump function....... virtually disappeared post partum, corresponding to the muscle pump normalization. No statistical correlation was found between venous muscle pump values and changes in hormone concentrations of estradiol, estriol and progesterone. It is suggested that venous insufficiency development in pregnancy is caused...

Endothelial heterogeneity in the umbilico-placental unit: DNA methylation as an innuendo of epigenetic diversity

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Casanello, Paola; Schneider, Daniela; Herrera, Emilio A.; Uauy, Ricardo; Krause, Bernardo J.

2014-01-01

The endothelium is a multifunctional heterogeneous tissue playing a key role in the physiology of every organ. To accomplish this role the endothelium presents a phenotypic diversity that is early prompted during vascular development, allowing it to cope with specific requirements in a time- and site-specific manner. During the last decade several reports show that endothelial diversity is also present in the umbilico-placental vasculature, with differences between macro- and microvascular vessels as well as arterial and venous endothelium. This diversity is evidenced in vitro as a higher angiogenic capacity in the microcirculation; or disparity in the levels of several molecules that control endothelial function (i.e., receptor for growth factors, vasoactive mediators, and adhesion molecules) which frequently are differentially expressed between arterial and venous endothelium. Emerging evidence suggests that endothelial diversity would be prominently driven by epigenetic mechanisms which also control the basal expression of endothelial-specific genes. This review outlines evidence for endothelial diversity since early stages of vascular development and how this heterogeneity is expressed in the umbilico-placental vasculature. Furthermore a brief picture of epigenetic mechanisms and their role on endothelial physiology emphasizing new data on umbilical and placental endothelial cells is presented. Unraveling the role of epigenetic mechanisms on long term endothelial physiology and its functional diversity would contribute to develop more accurate therapeutic interventions. Altogether these data show that micro- versus macro-vascular, or artery versus vein comparisons are an oversimplification of the complexity occurring in the endothelium at different levels, and the necessity for the future research to establish the precise source of cells which are under study. PMID:24723887

Endothelial heterogeneity in the umbilico-placental unit: DNA methylation as an innuendo of epigenetic diversity

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Paola eCasanello

2014-03-01

Full Text Available The endothelium is a multifunctional heterogeneous tissue playing a key role in the physiology of every organ. To accomplish this role the endothelium presents a phenotypic diversity that is early prompted during vascular development, allowing it to cope with specific requirements in a time- and site-specific manner. During the last decade several reports show that endothelial diversity is also present in the umbilico-placental vasculature, with differences between macro- and microvascular vessels as well as arterial and venous endothelium. This diversity is evidenced in vitro as a higher angiogenic capacity in the microcirculation; or disparity in the levels of several molecules that control endothelial function (i.e. receptor for growth factors, vasoactive mediators and adhesion molecules which frequently are differentially expressed between arterial and venous endothelium. Emerging evidence suggests that endothelial diversity would be prominently driven by epigenetic mechanisms which also control the basal expression of endothelial-specific genes. This review outlines evidence for endothelial diversity since early stages of vascular development and how this heterogeneity is expressed in the umbilico-placental vasculature. Furthermore a brief picture of epigenetic mechanisms and their role on endothelial physiology emphasising new data on umbilical and placental endothelial cells is presented. Unravelling the role of epigenetic mechanisms on long-term endothelial physiology and its functional diversity would contribute to develop more accurate therapeutic interventions. Altogether these data show that micro- versus macro-vascular, or artery versus vein comparisons are an oversimplification of the complexity occurring in the endothelium at different levels, and the necessity for the future research to establish the precise source of cells which are under study.

Venous function after pharmacomechanical thrombolysis for extensive iliofemoral deep vein thrombosis

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Wim Greeff

2017-08-01

Full Text Available Background: Chronic venous insufficiency is an important complication following iliofemoral deep venous thrombosis. Early thrombus removal may preserve venous function and prevent this complication. This study represents the largest reported South African series of pharmacomechanical thrombolysis for iliofemoral deep venous thrombosis to date. Objective: To evaluate the long-term outcome following pharmacomechanical thrombolysis for proximal and extensive deep venous thrombosis in a private, specialist vascular unit. Methods: All patients who underwent pharmacomechanical thrombolysis for iliofemoral deep venous thrombosis between August 2009 and January 2016 were invited to return for clinical assessment and venous ultrasound. Clinical findings were recorded according to the Villalta score and clinical, etiology, anatomic and pathology (CEAP classification. The quality of life (QoL was assessed utilising the VEINES-QoL/Sym questionnaire, providing two scores per patient, one describing the QoL and the other symptom severity (Sym. Results: Thirty two patients (35 legs were evaluated. There were 25 females and 7 males, with a mean age of 33.5 years (±14 years. The mean follow-up period was 31 months (range 3 months – 80 months. Results of the CEAP classification were C0 = 24 (75%, C1 = 1 (4%, C2 = 2 (6%, C3 = 2 (6% and C4 = 3 (9%. Thirty-one (97% patients had Villalta scores from 0 to 4, indicating no or mild evidence of venous disease. One patient (3% had a Villalta score of 6, indicating post-thrombotic syndrome. The mean QoL score was 87% (±12 and the mean Sym score was 86% (±14. Twenty-four (75% patients had no abnormality on ultrasound, with fibrosis the most observed abnormality. Conclusion: Most patients who had undergone pharmacomechanical thrombolysis for extensive iliofemoral deep venous thrombosis showed few significant clinical signs of chronic venous insufficiency, had excellent function on venous ultrasound and reported

Endothelial function and dysfunction: clinical significance and assessment

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Shaghayegh Haghjooyejavanmard

2008-08-01

Full Text Available

• Over the past two decades, investigators have increasingly recognized the importance of the endothelium as a centralregulator of vascular and body homeostasis. The endothelial lining represents an organ of 1.5 kg in an adult, which is distributed throughout the body. The endothelium is versatile and multifunctional. In addition to its role as a selective permeability barrier, it has many synthetic and metabolic properties, including modulation of vascular tone and blood flow, regulation of immune and inflammatory responses, and regulation of coagulation, fibrinolysis and thrombosis. Endothelial dysfunction (ED is a frequently used term, which can be referred to abnormalities in various physiological functions of the endothelium, and it is known as a key variable in the pathogenesis of several diseases and their complications. Finding suitable markers for endothelial damage or ED is certainly of interest. Established and emerging techniques to detect ED are divided into three large families of functional, cellular, and biochemical markers. Instead of performing single assessments, it may be much more valuable to determine various biological aspects of endothelium. It seems that there is likely a spectrum between normality, endothelial activation (by inflammatory cytokines, endothelial dysfunction (e.g., impairment of nitric oxide, resulting in loss of regulation of vascular tone and endothelial damage (e.g., atherosclerosis. In this review we review the importance of endothelium and its activation, biomarkers and dysfunction.
•  KEYWORDS: Endothelial function, endothelium, Disease.

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

Prediction of Liver Function by Using Magnetic Resonance-based Portal Venous Perfusion Imaging

Energy Technology Data Exchange (ETDEWEB)

Cao Yue, E-mail: yuecao@umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Wang Hesheng [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Johnson, Timothy D. [Department of Biostatistics, University of Michigan, Ann Arbor, Michigan (United States); Pan, Charlie [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Hussain, Hero [Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Balter, James M.; Normolle, Daniel; Ben-Josef, Edgar; Ten Haken, Randall K.; Lawrence, Theodore S.; Feng, Mary [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States)

2013-01-01

Purpose: To evaluate whether liver function can be assessed globally and spatially by using volumetric dynamic contrast-enhanced magnetic resonance imaging MRI (DCE-MRI) to potentially aid in adaptive treatment planning. Methods and Materials: Seventeen patients with intrahepatic cancer undergoing focal radiation therapy (RT) were enrolled in institution review board-approved prospective studies to obtain DCE-MRI (to measure regional perfusion) and indocyanine green (ICG) clearance rates (to measure overall liver function) prior to, during, and at 1 and 2 months after treatment. The volumetric distribution of portal venous perfusion in the whole liver was estimated for each scan. We assessed the correlation between mean portal venous perfusion in the nontumor volume of the liver and overall liver function measured by ICG before, during, and after RT. The dose response for regional portal venous perfusion to RT was determined using a linear mixed effects model. Results: There was a significant correlation between the ICG clearance rate and mean portal venous perfusion in the functioning liver parenchyma, suggesting that portal venous perfusion could be used as a surrogate for function. Reduction in regional venous perfusion 1 month after RT was predicted by the locally accumulated biologically corrected dose at the end of RT (P<.0007). Regional portal venous perfusion measured during RT was a significant predictor for regional venous perfusion assessed 1 month after RT (P<.00001). Global hypovenous perfusion pre-RT was observed in 4 patients (3 patients with hepatocellular carcinoma and cirrhosis), 3 of whom had recovered from hypoperfusion, except in the highest dose regions, post-RT. In addition, 3 patients who had normal perfusion pre-RT had marked hypervenous perfusion or reperfusion in low-dose regions post-RT. Conclusions: This study suggests that MR-based volumetric hepatic perfusion imaging may be a biomarker for spatial distribution of liver function, which

Hydrogen sulfide metabolism regulates endothelial solute barrier function

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Shuai Yuan

2016-10-01

Full Text Available Hydrogen sulfide (H2S is an important gaseous signaling molecule in the cardiovascular system. In addition to free H2S, H2S can be oxidized to polysulfide which can be biologically active. Since the impact of H2S on endothelial solute barrier function is not known, we sought to determine whether H2S and its various metabolites affect endothelial permeability. In vitro permeability was evaluated using albumin flux and transendothelial electrical resistance. Different H2S donors were used to examine the effects of exogenous H2S. To evaluate the role of endogenous H2S, mouse aortic endothelial cells (MAECs were isolated from wild type mice and mice lacking cystathionine γ-lyase (CSE, a predominant source of H2S in endothelial cells. In vivo permeability was evaluated using the Miles assay. We observed that polysulfide donors induced rapid albumin flux across endothelium. Comparatively, free sulfide donors increased permeability only with higher concentrations and at later time points. Increased solute permeability was associated with disruption of endothelial junction proteins claudin 5 and VE-cadherin, along with enhanced actin stress fiber formation. Importantly, sulfide donors that increase permeability elicited a preferential increase in polysulfide levels within endothelium. Similarly, CSE deficient MAECs showed enhanced solute barrier function along with reduced endogenous bound sulfane sulfur. CSE siRNA knockdown also enhanced endothelial junction structures with increased claudin 5 protein expression. In vivo, CSE genetic deficiency significantly blunted VEGF induced hyperpermeability revealing an important role of the enzyme for barrier function. In summary, endothelial solute permeability is critically regulated via exogenous and endogenous sulfide bioavailability with a prominent role of polysulfides.

Dietary phosphorus acutely impairs endothelial function.

Science.gov (United States)

Shuto, Emi; Taketani, Yutaka; Tanaka, Rieko; Harada, Nagakatsu; Isshiki, Masashi; Sato, Minako; Nashiki, Kunitaka; Amo, Kikuko; Yamamoto, Hironori; Higashi, Yukihito; Nakaya, Yutaka; Takeda, Eiji

2009-07-01

Excessive dietary phosphorus may increase cardiovascular risk in healthy individuals as well as in patients with chronic kidney disease, but the mechanisms underlying this risk are not completely understood. To determine whether postprandial hyperphosphatemia may promote endothelial dysfunction, we investigated the acute effect of phosphorus loading on endothelial function in vitro and in vivo. Exposing bovine aortic endothelial cells to a phosphorus load increased production of reactive oxygen species, which depended on phosphorus influx via sodium-dependent phosphate transporters, and decreased nitric oxide production via inhibitory phosphorylation of endothelial nitric oxide synthase. Phosphorus loading inhibited endothelium-dependent vasodilation of rat aortic rings. In 11 healthy men, we alternately served meals containing 400 mg or 1200 mg of phosphorus in a double-blind crossover study and measured flow-mediated dilation of the brachial artery before and 2 h after the meals. The high dietary phosphorus load increased serum phosphorus at 2 h and significantly decreased flow-mediated dilation. Flow-mediated dilation correlated inversely with serum phosphorus. Taken together, these findings suggest that endothelial dysfunction mediated by acute postprandial hyperphosphatemia may contribute to the relationship between serum phosphorus level and the risk for cardiovascular morbidity and mortality.

Rivaroxaban attenuates thrombosis by targeting the NF-κB signaling pathway in a rat model of deep venous thrombus.

Science.gov (United States)

Ma, Junhao; Li, Xinxi; Wang, Yang; Yang, Zhenwei; Luo, Jun

2017-12-01

Anticoagulant therapy is commonly used for the prevention and treatment of patients with deep venous thrombus. Evidence has shown that rivaroxaban is a potential oral anticoagulant drug for the acute treatment of venous thromboembolism. However, the rivaroxaban-mediated molecular mechanism involved in the progression of deep venous thrombosis has not been investigated. In the present study, we investigated the efficacy of rivaroxaban and the underlying signaling pathways in the prevention and treatment of rats with deep venous thrombosis. A rat model with deep vein thrombus formation was established and received treatment with rivaroxaban or PBS as control. The thrombin-activatable fibrinolysis inhibitor (TAFI) and plasminogen activator inhibitor-1 (PAI-1) were analyzed both in vitro and in vivo. The progression of thrombosis and stroke was evaluated after treatment with rivaroxaban or PBS. Nuclear factor-κB (NF-κB) signaling pathway in venous endothelial cells and in the rat model of deep venous thrombus was assessed. The therapeutic effects of rivaroxaban were evaluated as determined by changes in deep venous thrombosis in the rat model. Our results showed that rivaroxaban markedly inhibited TAFI and PAI-1 expression levels, neutrophils, tissue factor, neutrophil extracellular traps (NETs), myeloperoxidase and macrophages in venous endothelial cells and in the rat model of deep venous thrombus. Expression levels of ADP, PAIs, von Willebrand factor (vWF) and thromboxane were downregulated in vein endothelial cells and in serum from the experimental rats. Importantly, the incidences of inferior vena cava filter thrombus were protected by rivaroxaban during heparin-induced thrombolysis deep venous thrombosis in the rat model. We observed that activity of the NF-κB signaling pathway was inhibited by rivaroxaban in vein endothelial cells both in vitro and in vivo. Notably, immunohistology indicated that rivaroxaban attenuated deep venous thrombosis and the

Endothelial function and cardiovascular stress markers after a single dive in aging rats (ApoE knockout rats)

DEFF Research Database (Denmark)

Berenji Ardestani, Simin; Pedersen, Michael

Diving exposes body to a variety of stressors during the dive itself, and gas bubbles that develop during the decompression (ascent) phase. The compressed gas breath augments partial pressure of oxygen (PO2) causing the oxygen concentration of the blood to increase above normal (hyperoxia) likely...... causing excessive oxidative stress, including transient endothelial dysfunction in venous and arterial vessels....

Endothelial Function in Migraine With Aura – A Systematic Review

DEFF Research Database (Denmark)

Butt, Jawad H; Franzmann, Ulriche; Kruuse, Christina

2015-01-01

in migraineurs, and several studies on endothelial markers in the areas of inflammation, oxidative stress, and coagulation found increased endothelial activation in migraineurs, particularly in MA. One study, assessing cerebral endothelial function using transcranial Doppler sonography, reported lower...

Evaluation of the EndoPAT as a Tool to Assess Endothelial Function

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M. Moerland

2012-01-01

Endothelial function was stable over a longer period of time in renally impaired patients (coefficient of variation 13%. Endothelial function in renally impaired and type 2 diabetic patients was not decreased compared to healthy volunteers (2.9±1.4 and 1.8±0.3, resp., versus 1.8±0.5, P>0.05. The EndoPAT did not detect an effect of robust interventions on endothelial function in healthy volunteers (glucose load: change from baseline 0.08±0.50, 95% confidence interval −0.44 to 0.60; smoking: change from baseline 0.49±0.92, 95% confidence interval −0.47 to 1.46. This suggests that at present the EndoPAT might not be suitable to assess (changes in endothelial function in early-phase clinical pharmacology studies. Endothelial function as measured by the EndoPAT could be physiologically different from endothelial function as measured by conventional techniques. This should be investigated carefully before the EndoPAT can be considered a useful tool in drug development or clinical practice.

Endothelial function in male body builders taking anabolic androgenic steroids

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H Hashemi

2005-11-01

Full Text Available Background: Adverse cardiovascular events have been reported in body builders taking anabolic steroids. Adverse effects of AAS on endothelial function can initiate atherosclerosis. This study evaluates endothelial function in body builders using AAS, compared with non-steroids using athletes as controls. Methods: We recruited 30 nonsmoking male body builders taking AAS, 14 in build up phase, 8 in work out phase, and 8 in post steroid phase, and 30 nonsmoking male athletes who denied ever using steroids. Serum lipids and fasting plasma glucose were measured to exclude dyslipidemia and diabetes. Brachial artery diameter was measured by ultrasound at rest, after cuff inflation, and after sublingual glyceriltrinitrate (GTN to determine flow mediated dilation (FMD, nitro mediated dilation (NMD and ratio of FMD to NMD (index of endothelial function. Result: Use of AAS was associated with higher body mass index (BMI and low density lipoprotein–cholesterol (LDL-C. Mean ratio of flow mediated dilatation after cuff deflation to post GTN dilatation of brachial artery (index of endothelial function in body builders taking AAS was significantly lower than control group (0.96(0.05 versus 1(0.08; p=0.03. After adjusting BMI, age and weight, no significant difference was seen in index of endothelial function between two groups (p=0 .21. Conclusion: Our study indicates that taking AAS in body builders doesn’t have direct effect on endothelial function. Future study with bigger sample size and measurement of AAS metabolites is recommended. Key words: endothelium, lipids, anabolic steroids, body builders

Endothelial Function Is Associated with White Matter Microstructure and Executive Function in Older Adults

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Nathan F. Johnson

2017-08-01

Full Text Available Age-related declines in endothelial function can lead to cognitive decline. However, little is known about the relationships between endothelial function and specific neurocognitive functions. This study explored the relationship between measures of endothelial function (reactive hyperemia index; RHI, white matter (WM health (fractional anisotropy, FA, and WM hyperintensity volume, WMH, and executive function (Trail Making Test (TMT; Trail B − Trail A. Participants were 36 older adults between the ages of 59 and 69 (mean age = 63.89 years, SD = 2.94. WMH volume showed no relationship with RHI or executive function. However, there was a positive relationship between RHI and FA in the genu and body of the corpus callosum. In addition, higher RHI and FA were each associated with better executive task performance. Tractography was used to localize the WM tracts associated with RHI to specific portions of cortex. Results indicated that the RHI-FA relationship observed in the corpus callosum primarily involved tracts interconnecting frontal regions, including the superior frontal gyrus (SFG and frontopolar cortex, linked with executive function. These findings suggest that superior endothelial function may help to attenuate age-related declines in WM microstructure in portions of the corpus callosum that interconnect prefrontal brain regions involved in executive function.

Relationship between biomarkers of inflammation, oxidative stress and endothelial/microcirculatory function in successful aging versus healthy youth: a transversal study.

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Bottino, Daniel Alexandre; Lopes, Flávia Gomes; de Oliveira, Francisco José; Mecenas, Anete de Souza; Clapauch, Ruth; Bouskela, Eliete

2015-04-08

There is a functional decline of endothelial- dependent vasodilatation in the aging process. The aims of this study were to investigate if various microcirculatory parameters could correlate to anthropometrical variables, oxidative stress and inflammatory biomarkers in successful aging and compare the results to young healthy controls. Healthy elderly women (HE, 74.0 ± 8.7 years, n = 11) and young controls (YC, 23.1 ± 3.6 years, n = 24) were evaluated through nailfold videocapillaroscopy (NVC), venous occlusion plethysmography (VOP) and laboratorial analysis. Functional capillary density (FCD) and diameters, maximum red blood cell velocity (RBCVmax) during the reactive hyperemia response/RBCVbaseline after 1 min arterial occlusion at the finger base, time to reach RBCVmax were determined by NVC, peak increment of forearm blood flow (FBF) during the reactive hyperemia response (%Hyper) and after 0.4 mg sublingual nitroglycerin (%Nitro) by VOP and lipidogram, fibrinogen, fasting and postload glucose, oxidized LDL-cholesterol (oxLDL), sICAM, sVCAM, sE-Selectin, interleukines 1 and 6 and TNF-α by laboratorial analysis. Correlations and linear multiple regression (LMR) between %Hyper, %Nitro, microcirculatory parameters, oxidative stress and inflammatory biomarkers were investigated. sVCAM, sE-Selectin and oxLDL were higher and RBCVmax/RBCVbaseline and %Hyper lower in HE, while %Nitro and FCD remained unchanged. Fibrinogen, LDL-cholesterol, oxLDL correlated negatively to %Hyper while sVCAM correlated negatively to %Hyper and RBCVmax/RBCVbaseline. Healthy aged women presented dilated capillaries with sustained perfusion and endothelial dysfunction with preserved vascular smooth muscle reactivity. Fibrinogen, LDL-cholesterol, oxidized-LDL and sVCAM correlated negatively to endothelial function but not to microcirculatory parameters. Oxidized-LDL and sVCAM could determine %Hyper through LMR. Oxidized-LDL and sVCAM might be used as endothelial

deep venous thrombosis in patients with acute traumatic spinal cord ...

African Journals Online (AJOL)

endothelial injury (trauma) and immobility (venous stasis). DVT and ... pressure ulcers, spasticity and autonomic dysreflexia. (3). ... and its complications saves many lives. Accurate and ..... other chronic diseases and pre-existing risk factors.

Physical fitness and activity, metabolic profile, adipokines and endothelial function in children.

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Penha, Jociene Terra da; Gazolla, Fernanda Mussi; Carvalho, Cecília Noronha de Miranda; Madeira, Isabel Rey; Rodrigues-Junior, Flávio; Machado, Elisabeth de Amorim; Sicuro, Fernando Lencastre; Farinatti, Paulo; Bouskela, Eliete; Collett-Solberg, Paulo Ferrez

2018-05-29

The prevalence of obesity is increasing. The aim of this study was to investigate if there is endothelial dysfunction in children with normal or excess weight, and whether the metabolic profile, adipokines, and endothelial dysfunction would be more strongly associated with physical fitness or with physical activity levels. Cross-sectional study involving children aged 5-12 years. The evaluation included venous occlusion plethysmography, serum levels of adiponectin, leptin and insulin, lipid profile, physical activity score (PAQ-C questionnaire), and physical fitness evaluation (Yo-Yo test). A total of 62 children participated in this study. Based on the body mass index, 27 were eutrophic, 10 overweight and 25 obese. Triglycerides, LDL cholesterol, HOMA-IR, and leptin were higher in the obese and excess-weight groups compared to the eutrophic group (pPAQ-C. The Yo-Yo test was significantly associated with HDL cholesterol (rho=-0.41; p=0.01), and this association remained after adjusting for body mass index z-score (rho=0.28; p=0.03). This study showed that endothelial dysfunction is already present in obese children, suggesting a predisposition to atherosclerotic disease. Moreover, HDL cholesterol levels were correlated with physical fitness, regardless of body mass index. Copyright © 2018. Published by Elsevier Editora Ltda.

Microvascular endothelial function and cognitive performance: The ELSA-Brasil cohort study.

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Brant, Luisa; Bos, Daniel; Araujo, Larissa Fortunato; Ikram, M Arfan; Ribeiro, Antonio Lp; Barreto, Sandhi M

2018-06-01

Impaired microvascular endothelial function may be implicated in the etiology of cognitive decline. Yet, current data on this association are inconsistent. Our objective is to investigate the relation of microvascular endothelial function to cognitive performance in the ELSA-Brasil cohort study. A total of 1521 participants from ELSA-Brasil free of dementia underwent peripheral arterial tonometry (PAT) to quantify microvascular endothelial function (PAT-ratio and mean baseline pulse amplitude (BPA)) and cognitive tests that covered the domains of memory, verbal fluency, and executive function at baseline. Cognitive tests in participants aged 55 years old and above were repeated during the second examination (mean follow-up: 3.5 (0.3) years). Linear regression and generalized linear models were used to evaluate the association between endothelial function, global cognitive performance, and performance on specific cognitive domains. In unadjusted cross-sectional analyses, we found that BPA and PAT-ratio were associated with worse global cognitive performance (mean difference for BPA: -0.07, 95% CI: -0.11; -0.03, p<0.01; mean difference for PAT-ratio: 0.11, 95% CI: 0.01; 0.20, p=0.02), worse performance on learning, recall, and word recognition tests (BPA: -0.87, 95% CI: -1.21; -0.52, p<0.01; PAT-ratio: 1.58, 95% CI: 0.80; 2.36, p<0.01), and only BPA was associated with worse performance in verbal fluency tests (-0.70, 95% CI: -1.19; -0.21, p<0.01). Adjustments for age, sex, and level of education rendered the associations statistically non-significant. Longitudinally, there was no association between microvascular endothelial and cognitive functions. The associations between microvascular endothelial function and cognition are explained by age, sex, and educational level. Measures of microvascular endothelial function may be of limited value with regard to preclinical cognitive deficits.

Cerebral venous dynamics in newborn mice with intracranial hemorrhage studied using wavelets

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Pavlov, A. N.; Semyachkina-Glushkovskaya, O. V.; Sindeeva, O. A.; Pavlova, O. N.; Shuvalova, E. P.; Huang, Q.; Zhu, D.; Li, P.; Tuchin, V. V.; Luo, Q.

2015-03-01

We investigate the stress-induced development of the intracranial hemorrhage in newborn mice with the main attention to its latent stage. Our study is based on the laser speckle contrast imaging of the cerebral venous blood flow and the wavelet-based analysis of experimental data. We study responses of the sagittal sinus in different frequency ranges associated with distinct regulatory mechanisms and discuss significant changes of the spectral power in the frequency area associated with the NO-related endothelial function.

Effects of isokinetic calf muscle exercise program on muscle strength and venous function in patients with chronic venous insufficiency.

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Ercan, Sabriye; Çetin, Cem; Yavuz, Turhan; Demir, Hilmi M; Atalay, Yurdagül B

2018-05-01

Objective The aim of this study was to observe the change of the ankle joint range of motion, the muscle strength values measured with an isokinetic dynamometer, pain scores, quality of life scale, and venous return time in chronic venous insufficiency diagnosed patients by prospective follow-up after 12-week exercise program including isokinetic exercises. Methods The patient group of this study comprised 27 patients (23 female, 4 male) who were diagnosed with chronic venous insufficiency. An exercise program including isokinetic exercise for the calf muscle was given to patients three days per week for 12 weeks. At the end of 12 weeks, five of the patients left the study due to inadequate compliance with the exercise program. As a result, control data of 22 patients were included. Ankle joint range of active motion, isokinetic muscle strength, pain, quality of life, and photoplethysmography measurements were assessed before starting and after the exercise program. Results Evaluating changes of the starting and control data depending on time showed that all isokinetic muscle strength measurement parameters, range of motion, and overall quality of life values of patients improved. Venous return time values have also increased significantly ( p < 0.05). Conclusion In conclusion, increase in muscle strength has been provided with exercise therapy in patients with chronic venous insufficiency. It has been determined that the increase in muscle strength affected the venous pump and this ensured improvement in venous function and range of motion of the ankle. In addition, it has been detected that pain reduced and quality of life improved after the exercise program.

Atorvastatin affects negatively respiratory function of isolated endothelial mitochondria.

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Broniarek, Izabela; Jarmuszkiewicz, Wieslawa

2018-01-01

The purpose of this research was to elucidate the direct effects of two popular blood cholesterol-lowering drugs used to treat cardiovascular diseases, atorvastatin and pravastatin, on respiratory function, membrane potential, and reactive oxygen species formation in mitochondria isolated from human umbilical vein endothelial cells (EA.hy926 cell line). Hydrophilic pravastatin did not significantly affect endothelial mitochondria function. In contrast, hydrophobic calcium-containing atorvastatin induced a loss of outer mitochondrial membrane integrity, an increase in hydrogen peroxide formation, and reductions in maximal (phosphorylating or uncoupled) respiratory rate, membrane potential and oxidative phosphorylation efficiency. The atorvastatin-induced changes indicate an impairment of mitochondrial function at the level of ATP synthesis and at the level of the respiratory chain, likely at complex I and complex III. The atorvastatin action on endothelial mitochondria was highly dependent on calcium ions and led to a disturbance in mitochondrial calcium homeostasis. Uptake of calcium ions included in atorvastatin molecule induced mitochondrial uncoupling that enhanced the inhibition of the mitochondrial respiratory chain by atorvastatin. Our results indicate that hydrophobic calcium-containing atorvastatin, widely used as anti-atherosclerotic agent, has a direct negative action on isolated endothelial mitochondria. Copyright © 2017. Published by Elsevier Inc.

Mixed Capillary Venous Retroperitoneal Hemangioma

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Mohit Godar

2013-01-01

Full Text Available We report a case of mixed capillary venous hemangioma of the retroperitoneum in a 61-year-old man. Abdominal ultrasonography showed a mass to be hypoechoic with increased flow in color Doppler imaging. Dynamic contrast-enhanced computed tomography revealed a centripetal filling-in of the mass, located anterior to the left psoas muscle at the level of sacroiliac joint. On the basis of imaging features, preoperative diagnosis of hemangioma was considered and the mass was excised by laparoscopic method. Immunohistochemical studies were strongly positive for CD31 and CD34, and negative for calretinin, EMA, WT1, HMB45, Ki67, synaptophysin, and lymphatic endothelial cell marker D2–40. Histologically, the neoplasm was diagnosed as mixed capillary venous hemangioma.

Effect of orthostasis on endothelial function: a gender comparative study.

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Nandu Goswami

Full Text Available As the vascular endothelium has multiple functions, including regulation of vascular tone, it may play a role in the pathophysiology of orthostatic intolerance. We investigated the effect of orthostasis on endothelial function using EndoPAT®, a non-invasive and user-independent method, and across gender. As sex steroid hormones are known to affect endothelial function, this study examined the potential effect of these hormones on the endothelial response to orthostasis by including females at different phases of the menstrual cycle (follicular and luteal-where the hormone balance differs, and females taking an oral contraceptive. A total of 31 subjects took part in this study (11 males, 11 females having normal menstrual cycles and 9 females taking oral contraceptive. Each subject made two visits for testing; in the case of females having normal menstrual cycles the first session was conducted either 1-7 (follicular or 14-21 days (luteal after the start of menstruation, and the second session two weeks later, i.e., during the other phase, respectively. Endothelial function was assessed at baseline and following a 20-min orthostatic challenge (active standing. The EndoPAT® index increased from 1.71 ± 0.09 (mean ± SEM at baseline to 2.07 ± 0.09 following orthostasis in females (p<0.001. In males, the index increased from 1.60 ± 0.08 to 1.94 ± 0.13 following orthostasis (p<0.001. There were no significant differences, however, in the endothelial response to orthostasis between females and males, menstrual cycle phases and the usage of oral contraceptive. Our results suggest an increased vasodilatatory endothelial response following orthostasis in both females and males. The effect of gender and sex hormones on the endothelial response to orthostasis appears limited. Further studies are needed to determine the potential role of this post orthostasis endothelial response in the pathophysiology of orthostatic intolerance.

Endothelial function is unaffected by changing between carvedilol and metoprolol in patients with heart failure-a randomized study

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Køber Lars

2011-10-01

Full Text Available Abstract Background Carvedilol has been shown to be superior to metoprolol tartrate to improve clinical outcomes in patients with heart failure (HF, yet the mechanisms responsible for these differences remain unclear. We examined if there were differences in endothelial function, insulin stimulated endothelial function, 24 hour ambulatory blood pressure and heart rate during treatment with carvedilol, metoprolol tartrate and metoprolol succinate in patients with HF. Methods Twenty-seven patients with mild HF, all initially treated with carvedilol, were randomized to a two-month treatment with carvedilol, metoprolol tartrate or metoprolol succinate. Venous occlusion plethysmography, 24-hour blood pressure and heart rate measurements were done before and after a two-month treatment period. Results Endothelium-dependent vasodilatation was not affected by changing from carvedilol to either metoprolol tartrate or metoprolol succinate. The relative forearm blood flow at the highest dose of serotonin was 2.42 ± 0.33 in the carvedilol group at baseline and 2.14 ± 0.24 after two months continuation of carvedilol (P = 0.34; 2.57 ± 0.33 before metoprolol tartrate treatment and 2.42 ± 0.55 after treatment (p = 0.74 and in the metoprolol succinate group 1.82 ± 0.29 and 2.10 ± 0.37 before and after treatment, respectively (p = 0.27. Diurnal blood pressures as well as heart rate were also unchanged by changing from carvedilol to metoprolol tartrate or metoprolol succinate. Conclusion Endothelial function remained unchanged when switching the beta blocker treatment from carvedilol to either metoprolol tartrate or metoprolol succinate in this study, where blood pressure and heart rate also remained unchanged in patients with mild HF. Trial registration Current Controlled Trials NCT00497003

Endurance Capacity Is Not Correlated with Endothelial Function in Male University Students

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Wu, Fang; Su, Chen; Fan, Zhen-guo; Zhu, Zhu; Tao, Jun; Huang, Yi-jun

2014-01-01

Background Endurance capacity, assessed by 1000-meter (1000 m) run of male university students, is an indicator of cardiovascular fitness in Chinese students physical fitness surveillance. Although cardiovascular fitness is related to endothelial function closely in patients with cardiovascular diseases, it remains unclear whether endurance capacity correlates with endothelial function, especially with circulating endothelial microparticles (EMPs), a new sensitive marker of endothelial dysfunction in young students. The present study aimed to investigate the relationship between endurance capacity and endothelial function in male university students. Methods Forty-seven healthy male university students (mean age, 20.1±0.6 years; mean height, 172.4±6.3 cm; and mean weight, 60.0±8.2 kg) were recruited in this study. The measurement procedure of 1000 m run time was followed to Chinese national students Constitutional Health Criterion. Endothelium function was assessed by flow-mediated vasodilation (FMD) in the brachial artery measured by ultrasonic imaging, and the level of circulating EMPs was measured by flow cytometry. Cardiovascular fitness indicator - maximal oxygen uptake (VO2 max) - was also measured on a cycle ergometer using a portable gas analyzer. Results 1000 m run time was correlated with VO2max (r = −0.399, p0.05). Conclusion The correlations between endurance capacity or cardiovascular fitness and endothelial function were not found in healthy Chinese male university students. These results suggest that endurance capacity may not reflect endothelial function in healthy young adults with well preserved FMD and low level of circulating CD31+/CD42-EMPs. PMID:25101975

Homocyst(e)ine impairs endocardial endothelial function.

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Tyagi, S C; Smiley, L M; Mujumdar, V S

1999-12-01

Homocyst(e)ine injured vascular endothelium and modulated endothelial-dependent vascular function. Endothelium plays an analogous role in both the vessel and the endocardium. Therefore, we hypothesized that homocyst(e)ine modulated endocardial endothelium (EE) dependent cardiac function. The ex vivo cardiac rings from normal male Wistar-Kyoto rats were prepared. The contractile responses of left and right ventricular rings were measured in an isometric myobath, using different concentrations of CaCl2. The response was higher in the left ventricle than right ventricle and was elevated in endocardium without endothelium. The half effective concentration (EC50) and maximum tension generated by homocyst(e)ine were 10(6) and 5-fold lower than endothelin (ET) and angiotensin II (AII), respectively. However, in endothelial-denuded endocardium, homocyst(e)ine response was significantly increased (pine, and endothelial nitric oxide in EE function, cardiac rings were pretreated with AII (10(-10) M) or ET (10(-13) M) and then treated with homocyst(e)ine (10(-8) M). Results suggested that at these concentrations AII, ET, or homocyst(e)ine alone had no effect on cardiac contraction. However, in the presence of 10(-10) M AII or 10(-13) M ET, the cardiac contraction to homocyst(e)ine (10(-8) M) was significantly enhanced (pine. These results suggested that homocyst(e)ine impaired EE-dependent cardiac function and acted synergistically with AII and ET in enhancing the cardiac contraction.

Evaluation of the Effects of Different Energy Drinks and Coffee on Endothelial Function.

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Molnar, Janos; Somberg, John C

2015-11-01

Endothelial function plays an important role in circulatory physiology. There has been differing reports on the effect of energy drink on endothelial function. We set out to evaluate the effect of 3 energy drinks and coffee on endothelial function. Endothelial function was evaluated in healthy volunteers using a device that uses digital peripheral arterial tonometry measuring endothelial function as the reactive hyperemia index (RHI). Six volunteers (25 ± 7 years) received energy drink in a random order at least 2 days apart. Drinks studied were 250 ml "Red Bull" containing 80 mg caffeine, 57 ml "5-hour Energy" containing 230 mg caffeine, and a can of 355 ml "NOS" energy drink containing 120 mg caffeine. Sixteen volunteers (25 ± 5 years) received a cup of 473 ml coffee containing 240 mg caffeine. Studies were performed before drink (baseline) at 1.5 and 4 hours after drink. Two of the energy drinks (Red Bull and 5-hour Energy) significantly improved endothelial function at 4 hours after drink, whereas 1 energy drink (NOS) and coffee did not change endothelial function significantly. RHI increased by 82 ± 129% (p = 0.028) and 63 ± 37% (p = 0.027) after 5-hour Energy and Red Bull, respectively. The RHI changed after NOS by 2 ± 30% (p = 1.000) and by 7 ± 30% (p = 1.000) after coffee. In conclusion, some energy drinks appear to significantly improve endothelial function. Caffeine does not appear to be the component responsible for these differences. Copyright © 2015 Elsevier Inc. All rights reserved.

Functional and gene expression analysis of hTERT overexpressed endothelial cells

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Haruna Takano

2008-09-01

Full Text Available Haruna Takano1, Satoshi Murasawa1,2, Takayuki Asahara1,2,31Institute of Biomedical Research and Innovation, Kobe, Japan; 2RIKEN Center for Developmental Biology, Kobe 650-0047, Japan; 3Tokai University of School of Medicine, Tokai, JapanAbstract: Telomerase dysfunction contributes to cellular senescence. Recent advances indicate the importance of senescence in maintaining vascular cell function in vitro. Human telomerase reverse transcriptase (hTERT overexpression is thought to lead to resistance to apoptosis and oxidative stress. However, the mechanism in endothelial lineage cells is unclear. We tried to generate an immortal endothelial cell line from human umbilical vein endothelial cells using a no-virus system and examine the functional mechanisms of hTERT overexpressed endothelial cell senescence in vitro. High levels of hTERT genes and endothelial cell-specific markers were expressed during long-term culture. Also, angiogenic responses were observed in hTERT overexpressed endothelial cell. These cells showed a delay in senescence and appeared more resistant to stressed conditions. PI3K/Akt-related gene levels were enhanced in hTERT overexpressed endothelial cells. An up-regulated PI3K/Akt pathway caused by hTERT overexpression might contribute to anti-apoptosis and survival effects in endothelial lineage cells.Keywords: endothelial, telomerase, senescence, oxidative stress, anti-apoptosis, PI3K/Akt pathway

Obstructive sleep apnoea syndrome, endothelial function and markers of endothelialization. Changes after CPAP.

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Muñoz-Hernandez, Rocio; Vallejo-Vaz, Antonio J; Sanchez Armengol, Angeles; Moreno-Luna, Rafael; Caballero-Eraso, Candela; Macher, Hada C; Villar, Jose; Merino, Ana M; Castell, Javier; Capote, Francisco; Stiefel, Pablo

2015-01-01

This study tries to assess the endothelial function in vivo using flow-mediated dilatation (FMD) and several biomarkers of endothelium formation/restoration and damage in patients with obstructive sleep apnoea (OSA) syndrome at baseline and after three months with CPAP therapy. Observational study, before and after CPAP therapy. We studied 30 patients with apnoea/hypopnoea index (AHI) >15/h that were compared with themselves after three months of CPAP therapy. FMD was assessed non-invasively in vivo using the Laser-Doppler flowmetry. Circulating cell-free DNA (cf-DNA) and microparticles (MPs) were measured as markers of endothelial damage and the vascular endothelial growth factor (VEGF) was determined as a marker of endothelial restoration process. After three month with CPAP, FMD significantly increased (1072.26 ± 483.21 vs. 1604.38 ± 915.69 PU, pDNA and MPs significantly decreased (187.93 ± 115.81 vs. 121.28 ± 78.98 pg/ml, p<0.01, and 69.60 ± 62.60 vs. 39.82 ± 22.14 U/μL, p<0.05, respectively) and VEGF levels increased (585.02 ± 246.06 vs. 641.11 ± 212.69 pg/ml, p<0.05). These changes were higher in patients with more severe disease. There was a relationship between markers of damage (r = -0.53, p<0.005) but not between markers of damage and restoration, thus suggesting that both types of markers should be measured together. CPAP therapy improves FMD. This improvement may be related to an increase of endothelial restoration process and a decrease of endothelial damage.

The causes of skin damage and leg ulceration in chronic venous disease.

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Smith, Philip Coleridge

2006-09-01

Chronic venous disease with skin changes of the leg is a common condition affecting up to 1 in 20 people in westernized countries. The causes of this problem are not fully understood, although research in recent years has revealed a number of important mechanisms that contribute to the disease process. Patients with chronic venous disease suffer persistently raised pressures in their deep and superficial veins in the lower limb. Leucocytes become "trapped" in the circulation of the leg during periods of venous hyper-tension produced by sitting or standing. Studies of the plasma levels of neutrophil granule enzymes shows that these are increased during periods of venous hypertension, suggesting that this causes activation of the neutrophils. Investigation of the leucocyte surface ligands CD11b and CD62L shows that the more activated neutrophils and monocytes are sequestered during venous hypertension. Measurement of plasma levels of the soluble parts of the endothelial adhesion molecules VCAM, ICAM, and ELAM show that these are all elevated in patients with chronic venous disease compared to controls. Following 30 minutes of venous hypertension produced by standing, these levels are further increased. These data suggest that venous hypertension causes neutrophil and monocyte activation, which in turn causes injury to the endothelium. Chronic injury to the endothelium leads to a chronic inflammatory condition of the skin that we know clinically as lipodermatosclerosis. This is mediated by perivascular inflammatory cells, principally macrophages, in the skin microcirculation. These stimulate fibroblasts in the skin leading to tissue remodeling and laying down of fibrous tissue. Vascular endothelial growth factor stimulates proliferation of capillaries within the skin. Skin in this state has the potential to ulcerate in response to minor injury.

Assessing endothelial function and providing calibrated UFMD data using a blood pressure cuff

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Maltz, Jonathan S.

2017-08-22

Methods and apparatus are provided for assessing endothelial function in a mammal. In certain embodiments the methods involve using a cuff to apply pressure to an artery in a subject to determine a plurality of baseline values for a parameter related to endothelial function as a function of applied pressure (P.sub.m); b) applying a stimulus to the subject; and applying external pressure P.sub.m to the artery to determine a plurality of stimulus-effected values for the parameter related to endothelial function as a function of applied pressure (P.sub.m); where the baseline values are determined from measurements made when said mammal is not substantially effected by said stimulus and differences in said baseline values and said stimulus-effected values provide a measure of endothelial function in said mammal.

In smokers, Sonic hedgehog modulates pulmonary endothelial function through vascular endothelial growth factor.

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Henno, Priscilla; Grassin-Delyle, Stanislas; Belle, Emeline; Brollo, Marion; Naline, Emmanuel; Sage, Edouard; Devillier, Philippe; Israël-Biet, Dominique

2017-05-23

Tobacco-induced pulmonary vascular disease is partly driven by endothelial dysfunction. The Sonic hedgehog (SHH) pathway is involved in vascular physiology. We sought to establish whether the SHH pathway has a role in pulmonary endothelial dysfunction in smokers. The ex vivo endothelium-dependent relaxation of pulmonary artery rings in response to acetylcholine (Ach) was compared in 34 current or ex-smokers and 8 never-smokers. The results were expressed as a percentage of the contraction with phenylephrine. We tested the effects of SHH inhibitors (GANT61 and cyclopamine), an SHH activator (SAG) and recombinant VEGF on the Ach-induced relaxation. The level of VEGF protein in the pulmonary artery ring was measured in an ELISA. SHH pathway gene expression was quantified in reverse transcriptase-quantitative polymerase chain reactions. Ach-induced relaxation was much less intense in smokers than in never-smokers (respectively 24 ± 6% and 50 ± 7% with 10 -4 M Ach; p = 0.028). All SHH pathway genes were expressed in pulmonary artery rings from smokers. SHH inhibition by GANT61 reduced Ach-induced relaxation and VEGF gene expression in the pulmonary artery ring. Recombinant VEGF restored the ring's endothelial function. VEGF gene and protein expression levels in the pulmonary artery rings were positively correlated with the degree of Ach-induced relaxation and negatively correlated with the number of pack-years. SHH pathway genes and proteins are expressed in pulmonary artery rings from smokers, where they modulate endothelial function through VEGF.

Effects of physical training on endothelial function and limb blood flow in type 2 diabetes

DEFF Research Database (Denmark)

Sonne, Mette Paulli; Scheede-Bergdahl, Celena; Olsen, David Benee

2007-01-01

of physical training - or the opposite, inactivity - on endothelial function is not fully elucidated. Some studies have shown positive effects of physical training, whereas others have not. In general, physical training can improve endothelial function when this is impaired. However, physical training does...... not seem to have any effect on endothelial function when this is normal.......The term "endothelial dysfunction" refers to the inability or attenuated effect of the endothelial cells in participating in the relaxation of the adjacent smooth muscle, thus causing less vasodilation. Although endothelial dysfunction is often seen in patients with type 2 diabetes, it does...

Emulsifiers' composition modulates venous irritation of the nanoemulsions as a lipophilic and venous irritant drug delivery system.

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Mao, Chengwen; Wan, Jiangling; Chen, Huabing; Xu, Huibi; Yang, Xiangliang

2009-01-01

In this study, a nanoemulsion (NE) system was investigated for intravenous delivery of lipophilic and venous irritant drugs. NEs were prepared to deliver diallyl trisulfide (DT) for systemic therapy of bacterial and fungal infection, egg phospholipid was chosen as the main emulsifier, and two co-emulsifiers were also incorporated, including Poloxamer 188 (P188) and Solutol HS 15 (S15). Soybean oil was used as the dispersed phases, forming stable DT NEs with small particle sizes. The venous irritation of DT NEs was evaluated by in vitro human umbilical cord endothelial cells (CRL 1730) compatibility model with the intracellular adenosine triphosphate (ATP) and guanosine triphosphate (GTP) concentrations as the indices. The intracellular ATP and GTP reduction changed with the incorporation of a variety of co-emulsifiers, which varied in a free DT concentration-dependent manner. It was deduced that the free DT concentrations of NEs containing co-emulsifiers were determined by the partition coefficient of DT between oil and surfactant buffer solution. In conclusion, NE was an appropriate delivery system for lipophilic and venous irritant drug, and optimization of the composition of emulsifiers was an effective method to alleviate the venous irritation of DT NEs.

Obstructive sleep apnoea syndrome, endothelial function and markers of endothelialization. Changes after CPAP.

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Rocio Muñoz-Hernandez

Full Text Available This study tries to assess the endothelial function in vivo using flow-mediated dilatation (FMD and several biomarkers of endothelium formation/restoration and damage in patients with obstructive sleep apnoea (OSA syndrome at baseline and after three months with CPAP therapy.Observational study, before and after CPAP therapy.We studied 30 patients with apnoea/hypopnoea index (AHI >15/h that were compared with themselves after three months of CPAP therapy. FMD was assessed non-invasively in vivo using the Laser-Doppler flowmetry. Circulating cell-free DNA (cf-DNA and microparticles (MPs were measured as markers of endothelial damage and the vascular endothelial growth factor (VEGF was determined as a marker of endothelial restoration process.After three month with CPAP, FMD significantly increased (1072.26 ± 483.21 vs. 1604.38 ± 915.69 PU, p< 0.005 cf-DNA and MPs significantly decreased (187.93 ± 115.81 vs. 121.28 ± 78.98 pg/ml, p<0.01, and 69.60 ± 62.60 vs. 39.82 ± 22.14 U/μL, p<0.05, respectively and VEGF levels increased (585.02 ± 246.06 vs. 641.11 ± 212.69 pg/ml, p<0.05. These changes were higher in patients with more severe disease. There was a relationship between markers of damage (r = -0.53, p<0.005 but not between markers of damage and restoration, thus suggesting that both types of markers should be measured together.CPAP therapy improves FMD. This improvement may be related to an increase of endothelial restoration process and a decrease of endothelial damage.

The diagnostic value of endothelial function as a potential sensor of fatigue in health

Directory of Open Access Journals (Sweden)

Yoshiko Ohno

2010-03-01

Full Text Available Yoshiko Ohno1,2, Teruto Hashiguchi1, Ryuichi Maenosono1, Hidetoshi Yamashita3, Yukio Taira3, Kazufumi Minowa3, Yoshihito Yamashita3, Yuko Kato3, Ko-ichi Kawahara1, Ikuro Maruyama11Department of Laboratory and Vascular Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima City, Kagoshima Prefecture, Japan; 2Department of Community Health Nursing/Nursing Informatics, School of Health Sciences, Faculty of Medicine, Kagoshima University, Kagoshima City, Kagoshima Prefecture, Japan; 3Kagoshima Seikyo General Hospital, Kagoshima City, Kagoshima Prefecture, JapanPurpose: Many epidemiological research studies have shown that vital exhaustion and psychosocial factors are associated with the occurrence of cerebrocardiovascular disease (CCVD. Fatigue is thought to induce endothelial dysfunction and may be linked to the occurrence of CCVD; however, no studies have investigated this potential link. We studied to determine the effect of fatigue on endothelial function in healthy subjects with no traditional CCVD risk factors or potential confounding factors to be controlled.Subjects and methods: Peripheral arterial tonometry (PAT was used to evaluate endothelial function. The influence of the following parameters on endothelial function was analyzed in 74 office workers without traditional CCVD risk factors at health check-ups: endothelial function before and after work, subjective fatigue, lifestyle factors such as sleeping time, and psychosocial factors such as depression and social support.Results: Twenty-five subjects (33.8% had low endothelial function; reactive hyperemia (RH-PAT index <1.67, even though no abnormalities were reported in the health check-ups. There was no significant difference in endothelial function before versus after labor. Of note, endothelial function was associated with the individual’s level of subjective fatigue (t = 2.98, P = 0.008 and showed a daily fluctuation, sometimes to a pathological

Protective effects of dark chocolate on endothelial function and diabetes.

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Grassi, Davide; Desideri, Giovambattista; Ferri, Claudio

2013-11-01

Relationship between cocoa consumption and cardiovascular disease, particularly focusing on clinical implications resulting from the beneficial effects of cocoa consumption on endothelial function and insulin resistance. This could be of clinical relevance and may suggest the mechanistic explanation for the reduced risk of cardiovascular events reported in the different studies after cocoa intake. Increasing evidence supports a protective effect of cocoa consumption against cardiovascular disease. Cocoa and flavonoids from cocoa have been described to improve endothelial function and insulin resistance. A proposed mechanism could be considered in the improvement of the endothelium-derived vasodilator nitric oxide by enhancing nitric oxide synthesis or by decreasing nitric oxide breakdown. The endothelium plays a pivotal role in the arterial homeostasis, and insulin resistance is the most important pathophysiological feature in various prediabetic and diabetic states. Reduced nitric oxide bioavailability with endothelial dysfunction is considered the earliest step in the pathogenesis of atherosclerosis. Further, insulin resistance could account, at least in part, for the endothelial dysfunction. Endothelial dysfunction has been considered an important and independent predictor of future development of cardiovascular risk and events. Cocoa and flavonoids from cocoa might positively modulate these mechanisms with a putative role in cardiovascular protection.

Effect of onion peel extract on endothelial function and endothelial progenitor cells in overweight and obese individuals.

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Choi, Eun-Yong; Lee, Hansongyi; Woo, Jong Shin; Jang, Hyun Hee; Hwang, Seung Joon; Kim, Hyun Soo; Kim, Woo-Sik; Kim, Young-Seol; Choue, Ryowon; Cha, Yong-Jun; Yim, Jung-Eun; Kim, Weon

2015-09-01

Acute or chronic intake of polyphenol-rich foods has been reported to improve endothelial function. Quercetin, found abundantly in onion, is a potent antioxidant flavonoid. The aim of this study was to investigate whether consumption of onion peel extract (OPE) improves endothelial function in healthy overweight and obese individuals. This was a randomized double-blind, placebo-controlled study. Seventy-two healthy overweight and obese participants were randomly assigned to receive a red, soft capsule of OPE (100 mg quercetin/d, 50 mg quercetin twice daily; n = 36 participants) or an identical placebo capsule (n = 36) for 12 wk. Endothelial function, defined by flow-mediated dilation (FMD), circulating endothelial progenitor cells (EPCs) by flow cytometry, and laboratory test were determined at baseline and after treatment. Baseline characteristics and laboratory findings did not significantly differ between the two groups. Compared with baseline values, the OPE group showed significantly improved FMD at 12 wk (from 12.5 ± 5.2 to 15.2 ± 6.1; P = 0.002), whereas the placebo group showed no difference. Nitroglycerin-mediated dilation did not change in either group. EPC counts (44.2 ± 25.6 versus 52.3 ± 18.6; P = 0.005) and the percentage of EPCs were significantly increased in the OPE group. When FMD was divided into quartiles, rate of patients with endothelial dysfunction defined as lowest quartile (cutoff value, 8.6%) of FMD improved from 26% to 9% by OPE. Medium-term administration of OPE an improvement in FMD and circulating EPCs. Copyright © 2015 Elsevier Inc. All rights reserved.

Endothelial function in postmenopausal women with nighttime systolic hypertension.

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Routledge, Faye S; Hinderliter, Alan L; McFetridge-Durdle, Judith; Blumenthal, James A; Paine, Nicola J; Sherwood, Andrew

2015-08-01

Hypertension becomes more prevalent in women during their postmenopausal years. Nighttime systolic blood pressure (SBP) is especially predictive of adverse cardiac events, and the relationship between rising nighttime SBP and cardiovascular risk increases more rapidly in women compared with men. The reasons for the prognostic significance of nighttime SBP are not completely known but may involve vascular endothelial dysfunction. The purposes of this study were to examine the relationship between nighttime SBP and endothelial function, as assessed by brachial artery flow-mediated dilation (FMD), and to determine whether postmenopausal women with nighttime hypertension (SBP ≥120 mm Hg) evidenced greater endothelial dysfunction compared with women with normal nighttime SBP. One hundred postmenopausal women (mean [SD] age, 65.8 [7.5] y; mean [SD] body mass index, 28.3 [4.7] kg/m; hypertension, 47%; coronary artery disease, 51%; mean [SD] clinic SBP, 137 [17] mm Hg; mean [SD] clinic diastolic blood pressure, 67 [11] mm Hg; nighttime hypertension, 34 women) underwent 24-hour ambulatory blood pressure monitoring, actigraphy, and brachial artery FMD assessment. Multivariate regression models showed that higher nighttime SBP and larger baseline artery diameter were inversely related to FMD. Nighttime SBP and baseline artery diameter accounted for 23% of the variance in FMD. After adjustment for baseline artery diameter, women with nighttime hypertension had lower mean (SD) FMD than women with normal nighttime SBP (2.95% [0.65%] vs 5.52% [0.46%], P = 0.002). Nighttime hypertension is associated with reduced endothelial function in postmenopausal women. Research examining the therapeutic benefits of nighttime hypertension treatment on endothelial function and future cardiovascular risk in postmenopausal women is warranted.

Endothelial function is unaffected by changing between carvedilol and metoprolol in patients with heart failure--a randomized study

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Falskov, Britt; Hermann, Thomas Steffen; Raunsø, Jakob

2011-01-01

endothelial function, 24 hour ambulatory blood pressure and heart rate during treatment with carvedilol, metoprolol tartrate and metoprolol succinate in patients with HF. METHODS: Twenty-seven patients with mild HF, all initially treated with carvedilol, were randomized to a two-month treatment...... with carvedilol, metoprolol tartrate or metoprolol succinate. Venous occlusion plethysmography, 24-hour blood pressure and heart rate measurements were done before and after a two-month treatment period. RESULTS: Endothelium-dependent vasodilatation was not affected by changing from carvedilol to either...... metoprolol tartrate or metoprolol succinate. The relative forearm blood flow at the highest dose of serotonin was 2.42 ± 0.33 in the carvedilol group at baseline and 2.14 ± 0.24 after two months continuation of carvedilol (P = 0.34); 2.57 ± 0.33 before metoprolol tartrate treatment and 2.42 ± 0.55 after...

XIAP reverses various functional activities of FRNK in endothelial cells

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Ahn, Sunyoung; Kim, Hyun Jeong; Chi, Sung-Gil; Park, Heonyong

2012-01-01

Highlights: ► FRNK domain is recruited into focal adhesion (FA), controlling endothelial cell adhesion. ► XIAP binds the FRNK domain of FAK. ► XIAP inhibits recruitment of FRNK into Fas and FRNK-promoted cell adhesion. ► XIAP plays a key role in vascular functions of FRNK or FRNK domain-mediated vascular functions of FAK. -- Abstract: In endothelial cells, focal adhesion kinase (FAK) regulates cell proliferation, migration, adhesion, and shear-stimulated activation of MAPK. We recently found that FAK is recruited into focal adhesion (FA) sites through interactions with XIAP (X-chromosome linked inhibitor of apoptosis protein) and activated by Src kinase in response to shear stress. In this study, we examined which domain(s) of FAK is(are) important for various vascular functions such as FA recruiting, XIAP-binding and shear stress-stimulated ERK activation. Through a series of experiments, we determined that the FRNK domain is recruited into FA sites and promotes endothelial cell adhesion. Interestingly, XIAP knockdown was shown to reduce FA recruitment of FRNK and the cell adhesive effect of FRNK. In addition, we found that XIAP interacts with FRNK, suggesting cross-talk between XIAP and FRNK. We also demonstrated that FRNK inhibits endothelial cell migration and shear-stimulated ERK activation. These inhibitory effects of FRNK were reversed by XIAP knockdown. Taken together, we can conclude that XIAP plays a key role in vascular functions of FRNK or FRNK domain-mediated vascular functions of FAK.

Physiologically assessed hot flashes and endothelial function among midlife women.

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Thurston, Rebecca C; Chang, Yuefang; Barinas-Mitchell, Emma; Jennings, J Richard; von Känel, Roland; Landsittel, Doug P; Matthews, Karen A

2017-08-01

Hot flashes are experienced by most midlife women. Emerging data indicate that they may be associated with endothelial dysfunction. No studies have tested whether hot flashes are associated with endothelial function using physiologic measures of hot flashes. We tested whether physiologically assessed hot flashes were associated with poorer endothelial function. We also considered whether age modified associations. Two hundred seventy-two nonsmoking women reporting either daily hot flashes or no hot flashes, aged 40 to 60 years, and free of clinical cardiovascular disease, underwent ambulatory physiologic hot flash and diary hot flash monitoring; a blood draw; and ultrasound measurement of brachial artery flow-mediated dilation to assess endothelial function. Associations between hot flashes and flow-mediated dilation were tested in linear regression models controlling for lumen diameter, demographics, cardiovascular disease risk factors, and estradiol. In multivariable models incorporating cardiovascular disease risk factors, significant interactions by age (P hot flashes (beta [standard error] = -2.07 [0.79], P = 0.01), and more frequent physiologic hot flashes (for each hot flash: beta [standard error] = -0.10 [0.05], P = 0.03, multivariable) were associated with lower flow-mediated dilation. Associations were not accounted for by estradiol. Associations were not observed among the older women (age 54-60 years) or for self-reported hot flash frequency, severity, or bother. Among the younger women, hot flashes explained more variance in flow-mediated dilation than standard cardiovascular disease risk factors or estradiol. Among younger midlife women, frequent hot flashes were associated with poorer endothelial function and may provide information about women's vascular status beyond cardiovascular disease risk factors and estradiol.

Arterial endothelial function measurement method and apparatus

Energy Technology Data Exchange (ETDEWEB)

Maltz, Jonathan S; Budinger, Thomas F

2014-03-04

A "relaxoscope" (100) detects the degree of arterial endothelial function. Impairment of arterial endothelial function is an early event in atherosclerosis and correlates with the major risk factors for cardiovascular disease. An artery (115), such as the brachial artery (BA) is measured for diameter before and after several minutes of either vasoconstriction or vasorelaxation. The change in arterial diameter is a measure of flow-mediated vasomodification (FMVM). The relaxoscope induces an artificial pulse (128) at a superficial radial artery (115) via a linear actuator (120). An ultrasonic Doppler stethoscope (130) detects this pulse 10-20 cm proximal to the point of pulse induction (125). The delay between pulse application and detection provides the pulse transit time (PTT). By measuring PTT before (160) and after arterial diameter change (170), FMVM may be measured based on the changes in PTT caused by changes in vessel caliber, smooth muscle tone and wall thickness.

Non-pharmacological modification of endothelial function: An important lesson for clinical practice

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Monika Szulińska

2018-03-01

The impact of endothelial function in the complex pathology of cardiovascular diseases reflects a number of scientific proofs showing favorable effects of non-pharmacological interventions in endothelial dysfunction treatment.

Posttraumatic Stress Disorder Is Associated With Worse Endothelial Function Among Veterans.

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Grenon, S Marlene; Owens, Christopher D; Alley, Hugh; Perez, Sandra; Whooley, Mary A; Neylan, Thomas C; Aschbacher, Kirstin; Gasper, Warren J; Hilton, Joan F; Cohen, Beth E

2016-03-23

Current research in behavioral cardiology reveals a significant association between posttraumatic stress disorder (PTSD) and increased risk for cardiovascular disease and mortality; however, the underlying mechanisms remain poorly understood. We hypothesized that patients with PTSD would exhibit endothelial dysfunction, a potential mechanism involved in the development and progression of cardiovascular disease. A total of 214 outpatients treated at the San Francisco Veterans Affairs Medical Center underwent tests of endothelial function and evaluation for PTSD. Flow-mediated vasodilation of the brachial artery was performed to assess endothelial function, and current PTSD status was defined by the PTSD Checklist, based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition), with a score ≥40. Multivariable linear regression models were used to estimate the association between PTSD status and endothelial function. Patients with PTSD (n=67) were more likely to be male (99% versus 91%, P=0.04) and to have depression (58% versus 8%, P<0.0001) and were less likely to be on an angiotensin-converting enzyme inhibitor (17% versus 36%, P=0.007) or β-blocker treatment (25% versus 41%, P=0.03). Univariate analysis demonstrated that patients with PTSD had significantly lower flow-mediated vasodilation (5.8±3.4% versus 7.5±3.7%; P=0.003); furthermore, lower flow-mediated vasodilation was associated with increasing age (P=0.008), decreasing estimated glomerular filtration rate (P=0.003), hypertension (P=0.002), aspirin (P=0.03), and β-blocker treatments (P=0.01). In multivariable analysis, PTSD remained independently associated with lower flow-mediated vasodilation (P=0.0005). After adjusting for demographic, comorbidity, and treatment characteristics, PTSD remained associated with worse endothelial function in an outpatient population. Whether poor endothelial function contributes to the higher risk of cardiovascular disease in patients with PTSD

Endothelial function after 10 days of bed rest in individuals at risk for type 2 diabetes and cardiovascular disease

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Sonne, Mette Paulii; Højbjerre, Lise; Alibegovic, Amra C

2011-01-01

Aims: Physical inactivity is considered to be deleterious to vascular health, and in particular first degree relatives to patients with type 2 diabetes (FDR) and persons born with low birth weight (LBW) who may later in life develop cardiovascular disease. A period of imposed physical inactivity...... could unmask this risk. We hypothesized that the impact of physical inactivity on endothelial function would be more marked in subjects at increased risk for type 2 diabetes and cardiovascular disease, (LBW and FDR) compared with a matched control group (CON); all recruited via advertisements and via...... the Danish Birth Registry.Methods and Results: Twenty LBW and twenty CON and thirteen FDR were studied before and after ten days of bed rest. Forearm blood flow (FBF) was measured by venous occlusion plethysmography during brachial intra-arterial infusions of acetylcholine and adenosine at baseline...

Longitudinal assessment of maternal endothelial function and markers of inflammation and placental function throughout pregnancy in lean and obese mothers.

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Stewart, Frances M; Freeman, Dilys J; Ramsay, Jane E; Greer, Ian A; Caslake, Muriel; Ferrell, William R

2007-03-01

Obesity in pregnancy is increasing and is a risk factor for metabolic pathology such as preeclampsia. In the nonpregnant, obesity is associated with dyslipidemia, vascular dysfunction, and low-grade chronic inflammation. Our aim was to measure microvascular endothelial function in lean and obese pregnant women at intervals throughout their pregnancies and at 4 months after delivery. Plasma markers of endothelial function, inflammation, and placental function and their association with microvascular function were also assessed. Women in the 1st trimester of pregnancy were recruited, 30 with a body mass index (BMI) less than 30 kg/m(2) and 30 with a BMI more than or equal to 30 kg/m(2) matched for age, parity, and smoking status. In vivo endothelial-dependent and -independent microvascular function was measured using laser Doppler imaging in the 1st, 2nd, and 3rd trimesters of pregnancy and at 4 months postnatal. Plasma markers of endothelial activation [soluble intercellular cell adhesion molecule-1 (sVCAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), von Willebrand factor (vWF), and plasminogen activator inhibitor (PAI)-1], inflammation (IL-6, TNFalpha, C-reactive protein, and IL-10), and placental function (PAI-1/PAI-2 ratio) were also assessed at each time point. The pattern of improving endothelial function during pregnancy was the same for lean and obese, but endothelial-dependent vasodilation was significantly lower (P lean women but declined to near 1st trimester levels in the obese (lean/obese difference, 115%; P lean response being greater than obese (P = 0.021), and response declined in both groups in the postpartum period. In multivariate analysis, time of sampling had the most impact on endothelial-independent function [18.5% (adjusted sum of squares expressed as a percentage of total means squared), P lean 0.30 (0.21-0.47), P lean counterparts. There was a higher PAI-1/ PAI-2 ratio in the 1st trimester in obese women, which improved later in

Restoration of Endothelial Function in Pparα−/− Mice by Tempol

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Neerupma Silswal

2015-01-01

Full Text Available Peroxisome proliferator activated receptor alpha (PPARα is one of the PPAR isoforms belonging to the nuclear hormone receptor superfamily that regulates genes involved in lipid and lipoprotein metabolism. PPARα is present in the vascular wall and is thought to be involved in protection against vascular disease. To determine if PPARα contributes to endothelial function, conduit and cerebral resistance arteries were studied in Pparα−/− mice using isometric and isobaric tension myography, respectively. Aortic contractions to PGF2α and constriction of middle cerebral arteries to phenylephrine were not different between wild type (WT and Pparα−/−; however, relaxation/dilation to acetylcholine (ACh was impaired. There was no difference in relaxation between WT and Pparα−/− aorta to treatment with a nitric oxide (NO surrogate indicating impairment in endothelial function. Endothelial NO levels as well as NO synthase expression were reduced in Pparα−/− aortas, while superoxide levels were elevated. Two-week feeding with the reactive oxygen species (ROS scavenger, tempol, normalized ROS levels and rescued the impaired endothelium-mediated relaxation in Pparα−/− mice. These results suggest that Pparα−/− mice have impaired endothelial function caused by decreased NO bioavailability. Therefore, activation of PPARα receptors may be a therapeutic target for maintaining endothelial function and protection against cardiovascular disease.

Cornea stress test--evaluation of corneal endothelial function in vivo by contact lens induced stress

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Saini Jagjit

1997-01-01

Full Text Available Reliable and valid assessment of corneal endothelial function is a critical input for diagnosing, prognosticating and monitoring progression of disorders affecting corneal endothelium. In 123 eyes, corneal endothelial function was assessed employing data from the corneal hydration recovery dynamics. Serial pachometric readings were recorded on Haag-Striet pachometer with Mishima-Hedbys modification before and after two hours of thick soft contact lens wear. Percentage Recovery Per Hour (PRPH was derived from raw data as an index of endothelial function. Assessed PRPH in pseudophakic corneal oedema and Fuchs′ endothelial dystrophy eyes (35.9 +/- 9.8% was significantly lower than normal controls (61.9 +/- 10.5%. On employing receiver operation characteristics curve analysis the tested results demonstrated high sensitivity (87% and specificity (92% for detection of low endothelial function at PRPH cut off of 47.5%. Using this PRPH cut off, 80% of Fuchs′ endothelial dystrophy and 93.3% of pseudophakic corneal oedema eyes could be demonstrated to have low endothelial function. A total of 66.7% of diabetic eyes also demonstrated PRPH of lower than 47.5%. Clear corneal grafts demonstrated PRPH values of 24.6% to 73.0%. Of 6 corneal grafts that demonstrated initial PRPH of lower than 47.5%, 4 failed within 4 to 6 months. Our data demonstrated high sensitivity and specificity of this corneal stress test. PRPH index was useful in quantifying endothelial function in clinical disorders including diabetes mellitus. The index PRPH was demonstrated to be useful in monitoring and prognosticating outcome of corneal grafts.

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.

Endothelial function in highly endurance-trained and sedentary, healthy young women.

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Moe, Ingvild T; Hoven, Heidi; Hetland, Eva V; Rognmo, Oivind; Slørdahl, Stig A

2005-05-01

Endothelial function is reduced by age, chronic heart failure, coronary artery disease, hypertension or type 2 diabetes, and it is shown that aerobic exercise may reverse this trend. The effect of a high aerobic training status on endothelial function in young, healthy subjects is however less clear. The present study was designed to determine whether endothelial function is improved in highly endurance-trained young women compared to sedentary, healthy controls. Brachial artery diameter was measured in 16 endurance-trained (age: 23.7 +/- 2.5 years, maximal oxygen uptake (VO2max): 60.6 +/- 4.5 ml/kg per min) and 14 sedentary females (age: 23.7 +/- 2.1 years, VO2max: 40.5 +/- 5.6 ml/kg per min) at rest, during flow-mediated dilation (FMD) and after sublingual glycerol trinitrate administration, using high-resolution ultrasound. FMD did not differ between the endurance-trained and the sedentary females (14.8% vs 16.4%, p = NS), despite a substantial difference in VO2max of 50% (p endurance-trained group possessed however, a 9% larger resting brachial artery diameter when adjusted for body surface area. The results of the present study suggest that endothelial function is well preserved in young, healthy women, and that a high aerobic training status due to long term aerobic training does not improve the dilating capacity any further.

Inflammation and peripheral venous disease. The San Diego Population Study.

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Cushman, M; Callas, P W; Allison, M A; Criqui, M H

2014-09-02

The inflammatory response to healing in venous thrombosis might cause vein damage and post-thrombotic syndrome. Inflammation may also be involved in venous insufficiency apart from deep-vein thrombosis. We studied the association of inflammation markers with venous insufficiency in a general population sample. We characterised 2,404 men and women in a general population cohort for peripheral venous disease and its severity using physical exam, symptom assessment, and venous ultrasound. Inflammation markers, C-reactive protein (CRP), fibrinogen, interleukin 1-beta (IL-1-beta), IL-8, IL-10, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, monocyte chemoattractant-1 (MCP-1) and vascular endothelial cell growth factor (VEGF) were compared in 352 case participants with peripheral venous disease and 352 controls with no venous abnormalities frequency matched to cases by age, sex and race. Associations were also evaluated including a subset of 108 cases of severe venous disease, as previously defined. Odds ratios (95% CI), for peripheral venous disease for biomarkers in the top quartile (adjusting for age, race, sex, body mass index and history of venous thrombosis) were 1.8 (1.1-3.0), 1.6 (1.0-2.5) and 1.5 (0.9-2.3) for CRP, fibrinogen and IL-10, respectively. Associations were larger considering cases of severe venous disease, with odds ratios for these three analytes of 2.6 (1.2-5.9), 3.1 (1.3-7.3) and 2.2 (1.1-4.4), and for IL-8: 2.4 (1.1-5.2). There was no association of IL-1-beta, ICAM-1, VCAM-1, E-selectin, MCP-1 or VEGF with overall cases or severe venous disease. In conclusion, a subset of inflammation markers were associated with increased risk of peripheral venous disease, suggesting potential therapeutic targets for treatment.

The Effect of a Simulated Commercial Flight Environment with Hypoxia and Low Humidity on Clotting, Platelet, and Endothelial Function in Participants with Type 2 Diabetes – A Cross-over Study

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Judit Konya

2018-02-01

Full Text Available AimsTo determine if clotting, platelet, and endothelial function were affected by simulated short-haul commercial air flight conditions (SF in participants with type 2 diabetes (T2DM compared to controls.Methods10 participants with T2DM (7 females, 3 males and 10 controls (3 females, 7 males completed the study. Participants were randomized to either spend 2 h in an environmental chamber at sea level conditions (temperature: 23°C, oxygen concentration 21%, humidity 45%, or subject to a simulated 2-h simulated flight (SF: temperature: 23°C, oxygen concentration 15%, humidity 15%, and crossed over 7 days later. Main outcome measures: clot formation and clot lysis parameters, functional platelet activation markers, and endothelial function measured by reactive hyperemia index (RHI by EndoPAT and serum microparticles.ResultsComparing baseline with SF conditions, clot maximal absorption was increased in controls (0.375 ± 0.05 vs. 0.39 ± 0.05, p < 0.05 and participants with T2DM (0.378 ± 0.089 vs. 0.397 ± 0.089, p < 0.01, while increased basal platelet activation for both fibrinogen binding and P-selectin expression (p < 0.05 was seen in participants with T2DM. Parameters of clot formation and clot lysis, stimulated platelet function (stimulated platelet response to ADP and sensitivity to prostacyclin, and endothelial function were unchanged.ConclusionWhile SF resulted in the potential of denser clot formation with enhanced basal platelet activation in T2DM, the dynamic clotting, platelet, and endothelial markers were not affected, suggesting that short-haul commercial flying adds no additional hazard for venous thromboembolism for participants with T2DM compared to controls.

Quinapril treatment increases insulin-stimulated endothelial function and adiponectin gene expression in patients with type 2 diabetes

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Hermann, Thomas S; Li, Weijie; Dominguez, Helena

2005-01-01

OBJECTIVE: Angiotensin-converting enzyme inhibitors reduce cardiovascular mortality and improve endothelial function in type 2 diabetic patients. We hypothesized that 2 months of quinapril treatment would improve insulin-stimulated endothelial function and glucose uptake in type 2 diabetic subjects...... and simultaneously increase the expression of genes that are pertinent for endothelial function and metabolism. METHODS: Twenty-four type 2 diabetic subjects were randomized to receive 2 months of quinapril 20 mg daily or no treatment in an open parallel study. Endothelium-dependent and -independent vasodilation...... occlusion plethysmography. Gene expression was measured by real-time PCR. RESULTS: Quinapril treatment increased insulin-stimulated endothelial function in the type 2 diabetic subjects (P = 0.005), whereas forearm glucose uptake was unchanged. Endothelial function was also increased by quinapril (P = 0...

The effects of anti-obesity intervention with orlistat and sibutramine on microvascular endothelial function.

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Al-Tahami, Belqes Abdullah Mohammad; Ismail, Ab Aziz Al-Safi; Bee, Yvonne Tee Get; Awang, Siti Azima; Salha Wan Abdul Rani, Wan Rimei; Sanip, Zulkefli; Rasool, Aida Hanum Ghulam

2015-01-01

Obesity is associated with impaired microvascular endothelial function. We aimed to determine the effects of orlistat and sibutramine treatment on microvascular endothelial function, anthropometric and lipid profile, blood pressure (BP), and heart rate (HR). 76 subjects were recruited and randomized to receive orlistat 120 mg three times daily or sibutramine 10 mg daily for 9 months. Baseline weight, BMI, BP, HR and lipid profile were taken. Microvascular endothelial function was assessed using laser Doppler fluximetry and iontophoresis process. Maximum change (max), percent change (% change) and peak flux (peak) in perfusion to acetylcholine (ACh) and sodium nitroprusside (SNP) iontophoresis were used to quantify endothelium dependent and independent vasodilatations. 24 subjects in both groups completed the trial. After treatment, weight and BMI were decreased for both groups. AChmax, ACh % change and ACh peak were increased in orlistat-treated group but no difference was observed for sibutramine-treated group. BP and total cholesterol (TC) were reduced for orlistat-treated group. HR was reduced for orlistat-treated group but was increased in sibutramine-treated group. 9 months treatment with orlistat significantly improved microvascular endothelial function. This was associated with reductions in weight, BMI, BP, HR, TC and low density lipoprotein cholesterol. No effect was seen in microvascular endothelial function with sibutramine.

Nebivolol: impact on cardiac and endothelial function and clinical utility

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Toblli JE

2012-03-01

Full Text Available Jorge Eduardo Toblli1, Federico DiGennaro1, Jorge Fernando Giani2, Fernando Pablo Dominici21Hospital Aleman, 2Instituto de Química y Fisicoquímica Biológicas (IQUIFIB, Facultad de Farmacia y Bioquímica, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, ArgentinaAbstract: Endothelial dysfunction is a systemic pathological state of the endothelium characterized by a reduction in the bioavailability of vasodilators, essentially nitric oxide, leading to impaired endothelium-dependent vasodilation, as well as disarrangement in vascular wall metabolism and function. One of the key factors in endothelial dysfunction is overproduction of reactive oxygen species which participate in the development of hypertension, atherosclerosis, diabetes, cardiac hypertrophy, heart failure, ischemia-reperfusion injury, and stroke. Because impaired endothelial activity is believed to have a major causal role in the pathophysiology of vascular disease, hypertension, and heart failure, therapeutic agents which modify this condition are of clinical interest. Nebivolol is a third-generation β-blocker with high selectivity for β1-adrenergic receptors and causes vasodilation by interaction with the endothelial L-arginine/nitric oxide pathway. This dual mechanism of action underscores several hemodynamic qualities of nebivolol, which include reductions in heart rate and blood pressure and improvements in systolic and diastolic function. Although nebivolol reduces blood pressure to a degree similar to that of conventional β-blockers and other types of antihypertensive drugs, it may have advantages in populations with difficult-to-treat hypertension, such as patients with heart failure along with other comorbidities, like diabetes and obesity, and elderly patients in whom nitric oxide-mediated endothelial dysfunction may be more pronounced. Furthermore, recent data indicate that nebivolol appears to be a cost-effective treatment for elderly patients with

Endothelium-Derived 5-Methoxytryptophan Protects Endothelial Barrier Function by Blocking p38 MAPK Activation.

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Ling-Yun Chu

Full Text Available The endothelial junction is tightly controlled to restrict the passage of blood cells and solutes. Disruption of endothelial barrier function by bacterial endotoxins, cytokines or growth factors results in inflammation and vascular damage leading to vascular diseases. We have identified 5-methoxytryptophan (5-MTP as an anti-inflammatory factor by metabolomic analysis of conditioned medium of human fibroblasts. Here we postulated that endothelial cells release 5-MTP to protect the barrier function. Conditioned medium of human umbilical vein endothelial cells (HUVECs prevented endothelial hyperpermeability and VE-cadherin downregulation induced by VEGF, LPS and cytokines. We analyzed the metabolomic profile of HUVEC conditioned medium and detected 5-MTP but not melatonin, serotonin or their catabolites, which was confirmed by enzyme-linked immunosorbent assay. Addition of synthetic pure 5-MTP preserved VE-cadherin and maintained barrier function despite challenge with pro-inflammatory mediators. Tryptophan hydroxylase-1, an enzyme required for 5-MTP biosynthesis, was downregulated in HUVECs by pro-inflammatory mediators and it was accompanied by reduction of 5-MTP. 5-MTP protected VE-cadherin and prevented endothelial hyperpermeability by blocking p38 MAPK activation. A chemical inhibitor of p38 MAPK, SB202190, exhibited a similar protective effect as 5-MTP. To determine whether 5-MTP prevents vascular hyperpermeability in vivo, we evaluated the effect of 5-MTP administration on LPS-induced murine microvascular permeability with Evans blue. 5-MTP significantly prevented Evans blue dye leakage. Our findings indicate that 5-MTP is a new class of endothelium-derived molecules which protects endothelial barrier function by blocking p38 MAPK.

Effects of dark chocolate on endothelial function in patients with non-alcoholic steatohepatitis.

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Loffredo, L; Baratta, F; Ludovica, P; Battaglia, S; Carnevale, R; Nocella, C; Novo, M; Pannitteri, G; Ceci, F; Angelico, F; Violi, F; Del Ben, M

2018-02-01

Oxidative stress plays a pivotal role in inducing endothelial dysfunction and progression from simple fatty liver steatosis (FLD) to non-alcoholic steatohepatitis (NASH). Polyphenols could reduce oxidative stress and restore endothelial function by inhibiting the nicotinamide-adenine-dinucleotide-phosphate (NADPH) oxidase isoform Nox2. The aim of this study was to assess endothelial function and oxidative stress in a population affected by simple FLD and NASH. Furthermore, we analysed the effect of high vs low content of cocoa polyphenols on endothelial function and oxidative stress in patients with NASH. In a cross-sectional study we analysed endothelial function, as assessed by flow-mediated dilation (FMD), and oxidative stress, as assessed by Nox2 activation, serum isoprostanes and nitric oxide bioavailability (NOx), in patients with NASH (n = 19), FLD (n = 19) and controls (n = 19). Then, we performed a randomized, cross-over study in 19 subjects with NASH comparing the effect of 14-days administration of 40 g of chocolate at high (dark chocolate, cocoa >85%) versus low content (milk chocolate, cocoa chocolate. A simple linear regression analysis showed that Δ (expressed by difference of values between before and after 14 days of chocolate assumption) of FMD was associated with Δ of Nox2 activity (Rs = -0.323; p = 0.04), serum isoprostanes (Rs: -0.553; p < 0.001) and NOx (Rs: 0.557; p < 0.001). Cocoa polyphenols improve endothelial function via Nox2 down-regulation in NASH patients. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Characterisation of human induced pluripotent stem cell-derived endothelial cells under shear stress using an easy-to-use microfluidic cell culture system.

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Ohtani-Kaneko, Rsituko; Sato, Kenjiro; Tsutiya, Atsuhiro; Nakagawa, Yuka; Hashizume, Kazutoshi; Tazawa, Hidekatsu

2017-10-09

Induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) can contribute to elucidating the pathogenesis of heart and vascular diseases and developing their treatments. Their precise characteristics in fluid flow however remain unclear. Therefore, the aim of the present study is to characterise these features. We cultured three types of ECs in a microfluidic culture system: commercially available human iPS-ECs, human umbilical vein endothelial cells (HUVECs) and human umbilical artery endothelial cells (HUAECs). We then examined the mRNA expression levels of endothelial marker gene cluster of differentiation 31 (CD31), fit-related receptor tyrosine kinase (Flk-1), and the smooth muscle marker gene smooth muscle alpha-actin, and investigated changes in plasminogen activator inhibitor-1 (PAI-1) secretion and intracellular F-actin arrangement following heat stress. We also compared expressions of the arterial and venous marker genes ephrinB2 and EphB4, and the endothelial gap junction genes connexin (Cx) 37, 40, and 43 under fluidic shear stress to determine their arterial or venous characteristics. We found that iPS-ECs had similar endothelial marker gene expressions and exhibited similar increases in PAI-1 secretion under heat stress as HUVECs and HUAECs. In addition, F-actin arrangement in iPSC-ECs also responded to heat stress, as previously reported. However, they had different expression patterns of arterial and venous marker genes and Cx genes under different fluidic shear stress levels, showing that iPSC-ECs exhibit different characteristics from arterial and venous ECs. This microfluidic culture system equipped with variable shear stress control will provide an easy-to-use assay tool to examine characteristics of iPS-ECs generated by different protocols in various laboratories and contribute to basic and applied biomedical researches on iPS-ECs.

Folic acid: a marker of endothelial function in type 2 diabetes?

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Arduino A Mangoni

2005-04-01

Full Text Available Arduino A Mangoni1, Roy A Sherwood2, Belinda Asonganyi2, Emma L Ouldred3, Stephen Thomas4, Stephen HD Jackson31Department of Clinical Pharmacology, Centre for Neuroscience, School of Medicine, Flinders University, Adelaide, SA, Australia; 2Clinical Biochemistry, King’s College Hospital, London, UK; 3Department of Health Care of the Elderly, Guy’s, King’s, and St Thomas’ School of Medicine, King’s College, London, UK; 4Department of Diabetic Medicine, King’s College Hospital, London, UKObjectives: Endothelial dysfunction is a common feature of type 2 diabetes. Recent studies suggest that the B-vitamin folic acid exerts direct beneficial effects on endothelial function, beyond the well known homocysteine lowering effects. Therefore, folic acid might represent a novel “biomarker” of endothelial function. We sought to determine whether plasma levels of folic acid determine endothelial-dependent vasodilation in patients with type 2 diabetes.Methods: Forearm arterial blood flow (FABF was measured at baseline and during intrabrachial infusion of the endothelial-dependent vasodilator acetylcholine (15 µg/min and the endothelial-independent vasodilator sodium nitroprusside (2 µg/min in 26 type 2 diabetic patients (age 56.5 ± 0.9 years, means ± SEM with no history of cardiovascular disease.Results: FABF ratio (ie, the ratio between the infused and control forearm FABF significantly increased during acetylcholine (1.10 ± 0.04 vs 1.52 ± 0.07, p < 0.001 and sodium nitroprusside (1.12 ± 0.11 vs 1.62 ± 0.06, p < 0.001 infusions. After correcting for age, gender, diabetes duration, smoking, hypertension, body mass index, microalbuminuria, glycated hemoglobin, low-density lipoprotein cholesterol, and homocysteine, multiple regression analysis showed that plasma folic acid concentration was the only independent determinant (p = 0.037, R2 = 0.22 of acetylcholine-mediated, but not sodium nitroprusside-mediated, vasodilatation

Renal endothelial function and blood flow predict the individual susceptibility to adriamycin-induced renal damage

NARCIS (Netherlands)

Ochodnicky, Peter; Henning, Robert H.; Buikema, Hendrik; Kluppel, Alex C. A.; van Wattum, Marjolein; de Zeeuw, Dick; van Dokkum, Richard P. E.

Background. Susceptibility to renal injury varies among individuals. Previously, we found that individual endothelial function of healthy renal arteries in vitro predicted severity of renal damage after 5/6 nephrectomy. Here we hypothesized that individual differences in endothelial function in

Endothelial ERK signaling controls lymphatic fate specification

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Deng, Yong; Atri, Deepak; Eichmann, Anne; Simons, Michael

2013-01-01

Lymphatic vessels are thought to arise from PROX1-positive endothelial cells (ECs) in the cardinal vein in response to induction of SOX18 expression; however, the molecular event responsible for increased SOX18 expression has not been established. We generated mice with endothelial-specific, inducible expression of an RAF1 gene with a gain-of-function mutation (RAF1S259A) that is associated with Noonan syndrome. Expression of mutant RAF1S259A in ECs activated ERK and induced SOX18 and PROX1 expression, leading to increased commitment of venous ECs to the lymphatic fate. Excessive production of lymphatic ECs resulted in lymphangiectasia that was highly reminiscent of abnormal lymphatics seen in Noonan syndrome and similar “RASopathies.” Inhibition of ERK signaling during development abrogated the lymphatic differentiation program and rescued the lymphatic phenotypes induced by expression of RAF1S259A. These data suggest that ERK activation plays a key role in lymphatic EC fate specification and that excessive ERK activation is the basis of lymphatic abnormalities seen in Noonan syndrome and related diseases. PMID:23391722

Smoking Counteracts the Favorable Effect of Exercise Training on Endothelial Function in Patients with Type 2 Diabetes

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Shinji Sato

2013-01-01

Full Text Available Background Exercise training can improve endothelial function in patients with diabetes. We hypothesized that the favorable effect of exercise training on endothelial function in patients with diabetes is counteracted by cigarette smoking. Purpose To assess whether there is a difference in the effect of exercise on endothelial function in smokers and non-smokers with type 2 diabetes. Methods We performed a 3-month controlled trial in 27 never-smoking and 17 smoking individuals with type 2 diabetes who participated in a home-based walking program. The percentage decrease in post-exercise ankle-brachial pressure index (ABI, which is an index of endothelial function, was assessed at baseline and after 3 months. Results Compared to the smoking group, the never-smoking group showed a more significant improvement in post exercise ABI during the 3 months of home-based training (interaction, P < 0.01. Conclusions These results indicate that smoking may counteract the favorable effects of exercise training on endothelial function. Endothelial function plays an important role in the prevention of cardiovascular disease among patients with diabetes. Therefore, a Certified Diabetes Educator should strongly advise diabetic patients not to smoke.

Venous function in the leg after postoperative thrombosis diagnosed with 125I-fibrinogen uptake test

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Lindhagen, A.; Bergqvist, D.; Hallboeoek, T.; Efsing, H.O.

1983-01-01

The 125 I-fibrinogen uptake test (FUT) has been widely used in the past decade to detect postoperative thrombosis. FUT has been shown to correlate well with phlebography, and positive FUT is associated with a high frequency of pulmonary embolism. The long-term venous function of the leg after FUT-detected postoperative thrombosis, however, is inadequately documented. In 179 patients who had been studied after operation with FUT, a follow-up evaluation of FUT as an indicator of risk for development of deep venous insufficiency was made four to five years later. The patients replied to a questionnaire, were clinically examined, and underwent venous strain-gauge plethysmography, venous pressure measurement, and, in some cases, phlebography. No statistically significant differences were found in any of the parameters between legs that had been FUT-positive and those that were FUT-negative at the time of the operation. The frequency of deep venous insufficiency thus was equal in FUT-positive and FUT-negative legs. It was also independent of the site of FUT-detected thrombus in the leg

Sildenafil restores endothelial function in the apolipoprotein E knockout mouse

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Balarini Camille M

2013-01-01

Full Text Available Abstract Background Atherosclerosis is an inflammatory process of the arterial walls and is initiated by endothelial dysfunction accompanied by an imbalance in the production of reactive oxygen species (ROS and nitric oxide (NO. Sildenafil, a selective phosphodiesterase-5 (PDE5 inhibitor used for erectile dysfunction, exerts its cardiovascular effects by enhancing the effects of NO. The aim of this study was to investigate the influence of sildenafil on endothelial function and atherosclerosis progression in apolipoprotein E knockout (apoE−/− mice. Methods ApoE−/− mice treated with sildenafil (Viagra®, 40 mg/kg/day, for 3 weeks, by oral gavage were compared to the untreated apoE−/− and the wild-type (WT mice. Aortic rings were used to evaluate the relaxation responses to acetylcholine (ACh in all of the groups. In a separate set of experiments, the roles of NO and ROS in the relaxation response to ACh were evaluated by incubating the aortic rings with L-NAME (NO synthase inhibitor or apocynin (NADPH oxidase inhibitor. In addition, the atherosclerotic lesions were quantified and superoxide production was assessed. Results Sildenafil restored the vasodilator response to acetylcholine (ACh in the aortic rings of the apoE−/− mice. Treatment with L-NAME abolished the vasodilator responses to ACh in all three groups of mice and revealed an augmented participation of NO in the endothelium-dependent vasodilation in the sildenafil-treated animals. The normalized endothelial function in sildenafil-treated apoE−/− mice was unaffected by apocynin highlighting the low levels of ROS production in these animals. Moreover, morphological analysis showed that sildenafil treatment caused approximately a 40% decrease in plaque deposition in the aorta. Conclusion This is the first study demonstrating the beneficial effects of chronic treatment with sildenafil on endothelial dysfunction and atherosclerosis in a model of spontaneous

Renal endothelial function and blood flow predict the individual susceptibility to adriamycin-induced renal damage

NARCIS (Netherlands)

Ochodnicky, Peter; Henning, Robert H.; Buikema, Hendrik; Kluppel, Alex C. A.; van Wattum, Marjolein; de Zeeuw, Dick; van Dokkum, Richard P. E.

2009-01-01

Susceptibility to renal injury varies among individuals. Previously, we found that individual endothelial function of healthy renal arteries in vitro predicted severity of renal damage after 5/6 nephrectomy. Here we hypothesized that individual differences in endothelial function in vitro and renal

Androgen Modulates Functions of Endothelial Progenitor Cells through Activated Egr1 Signaling

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Yizhou Ye

2016-01-01

Full Text Available Researches show that androgens have important effects on migration of endothelial cells and endothelial protection in coronary heart disease. Endothelial progenitor cells (EPCs as a progenitor cell type that can differentiate into endothelial cells, have a critical role in angiogenesis and endothelial protection. The relationship between androgen and the functions of EPCs has animated much interest and controversy. In this study, we investigated the angiogenic and migratory functions of EPCs after treatment by dihydrotestosterone (DHT and the molecular mechanisms as well. We found that DHT treatment enhanced the incorporation of EPCs into tubular structures formed by HUVECs and the migratory activity of EPCs in the transwell assay dose dependently. Moreover, microarray analysis was performed to explore how DHT changes the gene expression profiles of EPCs. We found 346 differentially expressed genes in androgen-treated EPCs. Angiogenesis-related genes like Egr-1, Vcan, Efnb2, and Cdk2ap1 were identified to be regulated upon DHT treatment. Furthermore, the enhanced angiogenic and migratory abilities of EPCs after DHT treatment were inhibited by Egr1-siRNA transfection. In conclusion, our findings suggest that DHT markedly enhances the vessel forming ability and migration capacity of EPCs. Egr1 signaling may be a possible pathway in this process.

A Single Resistance Exercise Session Improves Aortic Endothelial Function in Hypertensive Rats

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Thaís de Oliveira Faria

Full Text Available Abstract Background: Physical exercise is an important tool for the improvement of endothelial function. Objective: To assess the effects of acute dynamic resistance exercise on the endothelial function of spontaneously hypertensive rats (SHR. Methods: Ten minutes after exercise, the aorta was removed to evaluate the expression of endothelial nitric oxide synthase (eNOS, phosphorylated endothelial nitric oxide synthase (p-eNOS1177 and inducible nitric oxide synthase (iNOS and to generate concentration-response curves to acetylcholine (ACh and to phenylephrine (PHE. The PHE protocol was also performed with damaged endothelium and before and after NG-nitro-L-arginine methyl ester (L-NAME and indomethacin administration. The maximal response (Emax and the sensitivity (EC50 to these drugs were evaluated. Results: ACh-induced relaxation increased in the aortic rings of exercised (Ex rats (Emax= -80 ± 4.6%, p < 0.05 when compared to those of controls (Ct (Emax = -50 ± 6.8%. The Emax to PHE was decreased following exercise conditions (95 ± 7.9%, p < 0.05 when compared to control conditions (120 ± 4.2%. This response was abolished after L-NAME administration or endothelial damage. In the presence of indomethacin, the aortic rings' reactivity to PHE was decreased in both groups (EC50= Ex -5.9 ± 0.14 vs. Ct -6.6 ± 0.33 log µM, p < 0.05 / Emax = Ex 9.5 ± 2.9 vs. Ct 17 ± 6.2%, p < 0.05. Exercise did not alter the expression of eNOS and iNOS, but increased the level of p-eNOS. Conclusion: A single resistance exercise session improves endothelial function in hypertensive rats. This response seems to be mediated by increased NO production through eNOS activation.

High-intensity Interval training enhances mobilization/functionality of endothelial progenitor cells and depressed shedding of vascular endothelial cells undergoing hypoxia.

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Tsai, Hsing-Hua; Lin, Chin-Pu; Lin, Yi-Hui; Hsu, Chih-Chin; Wang, Jong-Shyan

2016-12-01

Exercise training improves endothelium-dependent vasodilation, whereas hypoxic stress causes vascular endothelial dysfunction. Monocyte-derived endothelial progenitor cells (Mon-EPCs) contribute to vascular repair process by differentiating into endothelial cells. This study investigates how high-intensity interval (HIT) and moderate-intensity continuous (MCT) exercise training affect circulating Mon-EPC levels and EPC functionality under hypoxic condition. Sixty healthy sedentary males were randomized to engage in either HIT (3-min intervals at 40 and 80 % VO 2max for five repetitions, n = 20) or MCT (sustained 60 % VO 2max , n = 20) for 30 min/day, 5 days/week for 6 weeks, or to a control group (CTL) that did not received exercise intervention (n = 20). Mon-EPC characteristics and EPC functionality under hypoxic exercise (HE, 100 W under 12 % O 2 ) were determined before and after HIT, MCT, and CTL. The results demonstrated that after the intervention, the HIT group exhibited larger improvements in VO 2peak , estimated peak cardiac output (Q C ), and estimated peak perfusions of frontal cerebral lobe (Q FC ) and vastus lateralis (Q VL ) than the MCT group. Furthermore, HIT (a) increased circulating CD14 ++ /CD16 - /CD34 + /KDR + (Mon-1 EPC) and CD14 ++ /CD16 + /CD34 + /KDR + (Mon-2 EPC) cell counts, (b) promoted the migration and tube formation of EPCs, (c) diminished the shedding of endothelial (CD34 - /KDR + /phosphatidylserine + ) cells, and (d) elevated plasma nitrite plus nitrate, stromal cell-derived factor-1, matrix metalloproteinase-9, and vascular endothelial growth factor-A concentrations at rest or following HE, compared to those of MCT. In addition, Mon-1 and -2 EPC counts were directly related to VO 2peak and estimated peak Q C , Q FC , and Q VL . HIT is superior to MCT for improving hemodynamic adaptation and Mon-EPC production. Moreover, HIT effectively enhances EPC functionality and suppresses endothelial injury undergoing hypoxia.

Assessment of macrovascular endothelial function using pulse wave analysis and its association with microvascular reactivity in healthy subjects.

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Ibrahim, N N I N; Rasool, A H G

2017-08-01

Pulse wave analysis (PWA) and laser Doppler fluximetry (LDF) are non-invasive methods of assessing macrovascular endothelial function and microvascular reactivity respectively. The aim of this study was to assess the correlation between macrovascular endothelial function assessed by PWA and microvascular reactivity assessed by LDF. 297 healthy and non-smoking subjects (159 females, mean age (±SD) 23.56 ± 4.54 years) underwent microvascular reactivity assessment using LDF followed by macrovascular endothelial function assessments using PWA. Pearson's correlation showed no correlation between macrovascular endothelial function and microvascular reactivity (r = -0.10, P = 0.12). There was no significant correlation between macrovascular endothelial function assessed by PWA and microvascular reactivity assessed by LDF in healthy subjects. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Asymmetric dimethyl-L-arginine (ADMA): a possible link between homocyst(e)ine and endothelial dysfunction.

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Stühlinger, Markus C; Stanger, Olaf

2005-02-01

Hyperhomocyst(e)inemia is associated with an increased risk for atherosclerotic disease and venous thromboembolism. The impact of elevated plasma homocysteine levels seems to be clinically relevant, since the total cardiovascular risk of hyperhomocyst(e)inemia is comparable to the risk associated with hyperlipidemia or smoking. There is substantial evidence for impairment of endothelial function in human and animal models of atherosclerosis, occurring even before development of overt plaques. Interestingly endothelial dysfunction appears to be a sensitive indicator of the process of atherosclerotic lesion development and predicts future vascular events. NO is the most potent endogenous vasodilator known. It is released by the endothelium, and reduced NO bioavailability is responsible for impaired endothelium-dependent vasorelaxation in hyperhomocyst(e)inemia and other metabolic disorders associated with vascular disease. Substances leading to impaired endothelial function as a consequence of reduced NO generation are endogenous NO synthase inhibitors such as ADMA. Indeed there is accumulating evidence from animal and human studies that ADMA, endothelial function and homocyst(e)ine might be closely interrelated. Specifically elevations of ADMA associated with impaired endothelium-dependent relaxation were found in chronic hyperhomocyst(e)inemia, as well as after acute elevation of plasma homocyst(e)ine following oral methionine intake. The postulated mechanisms for ADMA accumulation are increased methylation of arginine residues within proteins, as well as reduced metabolism of ADMA by the enzyme DDAH, but they still need to be confirmed to be operative in vivo. Hyperhomocyst(e)inemia, as well as subsequent endothelial dysfunction can be successfully treated by application of folate and B vitamins. Since ADMA seems to play a central role in homocyst(e)ine-induced endothelial dysfunction, another way of preventing vascular disease in patients with elevated homocyst

Endothelial plasticity in cardiovascular development : role of growth factors VEGF and PDGF

NARCIS (Netherlands)

Akker, Nynke Margaretha Sophie van den

2008-01-01

The central cell type within vascular development is the endothelial cell (EC). It forms during (lymph)vasculogenesis, proliferates during angiogenesis and instructs medial cells during arteriogenesis. The venous population also gives rise to a subset of the lymphatic endothelium and the endocardium

Effects of acute and chronic attenuation of postprandial hyperglycemia on postglucose-load endothelial function in insulin resistant individuals: is stimulation of first phase insulin secretion beneficial for the endothelial function?

DEFF Research Database (Denmark)

Major-Pedersen, A; Ihlemann, N; Hermann, T S

2008-01-01

The aim of the study is to determine if attenuation of postprandial hyperglycemia, by acutely and chronically enhancing postprandial insulin secretion in insulin-resistant individuals, improves the endothelial dysfunction. We assessed postoral glucose-load endothelial function in 56 insulin....... We found no relationship between postprandial hyperglycemia and post-OGL FMD....

Enhanced endothelial cell functions on rosette nanotube-coated titanium vascular stents

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Eli Fine

2009-04-01

Full Text Available Eli Fine1, Lijie Zhang1, Hicham Fenniri2, Thomas J Webster1 1Department of Engineering, Brown University, Providence, RI, USA; 2National Institute for Nanotechnology and Department of Chemistry, University of Alberta, Edmonton, AB, CanadaAbstract: One of the main problems with current vascular stents is a lack of endothelial cell interactions, which if sufficient, would create a uniform healthy endothelium masking the underlying foreign metal from inflammatory cell interference. Moreover, if endothelial cells from the arterial wall do not adhere to the stent, the stent can become loose and dislodge. Therefore, the objective of this in vitro study was to design a novel biomimetic nanostructured coating (that does not contain drugs on conventional vascular stent materials (specifically, titanium for improving vascular stent applications. Rosette nanotubes (RNTs are a new class of biomimetic nanotubes that self-assemble from DNA base analogs and have been shown in previous studies to sufficiently coat titanium and enhance osteoblast cell functions. RNTs have many desirable properties for use as vascular stent coatings including spontaneous self-assembly in body fluids, tailorable surface chemistry for specific implant applications, and nanoscale dimensions similar to those of the natural vascular extracellular matrix. Importantly, the results of this study provided the first evidence that RNTs functionalized with lysine (RNT–K, even at low concentrations, significantly increase endothelial cell density over uncoated titanium. Specifically, 0.01 mg/mL RNT–K coated titanium increased endothelial cell density by 37% and 52% compared to uncoated titanium after 4 h and three days, respectively. The excellent cytocompatibility properties of RNTs (as demonstrated here for the first time for endothelial cells suggest the need for the further exploration of these novel nanostructured materials for vascular stent applications.Keywords: stents

Endothelial function in pre-pubertal children at risk of developing cardiomyopathy: a new frontier

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Aline Cristina Tavares

2012-01-01

Full Text Available Although it is known that obesity, diabetes, and Kawasaki's disease play important roles in systemic inflammation and in the development of both endothelial dysfunction and cardiomyopathy, there is a lack of data regarding the endothelial function of pre-pubertal children suffering from cardiomyopathy. In this study, we performed a systematic review of the literature on pre-pubertal children at risk of developing cardiomyopathy to assess the endothelial function of pre-pubertal children at risk of developing cardiomyopathy. We searched the published literature indexed in PubMed, Bireme and SciELO using the keywords 'endothelial', 'children', 'pediatric' and 'infant' and then compiled a systematic review. The end points were age, the pubertal stage, sex differences, the method used for the endothelial evaluation and the endothelial values themselves. No studies on children with cardiomyopathy were found. Only 11 papers were selected for our complete analysis, where these included reports on the flow-mediated percentage dilatation, the values of which were 9.80±1.80, 5.90±1.29, 4.50±0.70, and 7.10±1.27 for healthy, obese, diabetic and pre-pubertal children with Kawasaki's disease, respectively. There was no significant difference in the dilatation, independent of the endothelium, either among the groups or between the genders for both of the measurements in children; similar results have been found in adolescents and adults. The endothelial function in cardiomyopathic children remains unclear because of the lack of data; nevertheless, the known dysfunctions in children with obesity, type 1 diabetes and Kawasaki's disease may influence the severity of the cardiovascular symptoms, the prognosis, and the mortality rate. The results of this study encourage future research into the consequences of endothelial dysfunction in pre-pubertal children.

Diagnosis of venous disorders

International Nuclear Information System (INIS)

Minar, E.

1993-01-01

Limited accuracy in the clinic diagnosis of deep vein thrombosis (VT) makes such diagnostic tests such as duplex sonography or venography necessary. Exact information on the age and extent of the thrombus are necessary for the clinician to optimize the therapeutric management. The correct diagnosis of calf vein thrombosis and of recurrent VT in patients with postphlebitis changes also has implications for treatment. After exclusion of thrombosis, the radiologist should evaluate the leg for other possible causes of symptoms besides VT. Investigation of the venous sytem also has a role in the diagnosis in patients with suspected pulmonary embolism. In patients with chronic venous insuffficiency the deep venous system should assessed for patency and venous valve function. The superficial veins should be differentiated in segments with sufficient or insufficient venous valves, and it is also necessary to look for insufficiency of the perforrating veins. In patients with superficial phlebitis there is risk of propagation into the deep venous system. (orig.) [de

Percutaneous Mitral Valve Repair in Mitral Regurgitation Reduces Cell-Free Hemoglobin and Improves Endothelial Function.

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Christos Rammos

Full Text Available Endothelial dysfunction is predictive for cardiovascular events and may be caused by decreased bioavailability of nitric oxide (NO. NO is scavenged by cell-free hemoglobin with reduction of bioavailable NO up to 70% subsequently deteriorating vascular function. While patients with mitral regurgitation (MR suffer from an impaired prognosis, mechanisms relating to coexistent vascular dysfunctions have not been described yet. Therapy of MR using a percutaneous mitral valve repair (PMVR approach has been shown to lead to significant clinical benefits. We here sought to investigate the role of endothelial function in MR and the potential impact of PMVR.Twenty-seven patients with moderate-to-severe MR treated with the MitraClip® device were enrolled in an open-label single-center observational study. Patients underwent clinical assessment, conventional echocardiography, and determination of endothelial function by measuring flow-mediated dilation (FMD of the brachial artery using high-resolution ultrasound at baseline and at 3-month follow-up. Patients with MR demonstrated decompartmentalized hemoglobin and reduced endothelial function (cell-free plasma hemoglobin in heme 28.9±3.8 μM, FMD 3.9±0.9%. Three months post-procedure, PMVR improved ejection fraction (from 41±3% to 46±3%, p = 0.03 and NYHA functional class (from 3.0±0.1 to 1.9±1.7, p<0.001. PMVR was associated with a decrease in cell free plasma hemoglobin (22.3±2.4 μM, p = 0.02 and improved endothelial functions (FMD 4.8±1.0%, p<0.0001.We demonstrate here that plasma from patients with MR contains significant amounts of cell-free hemoglobin, which is accompanied by endothelial dysfunction. PMVR therapy is associated with an improved hemoglobin decompartmentalization and vascular function.

Urinary Leukotriene E4 Is Associated with Renal Function but Not with Endothelial Function in Type 2 Diabetes

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Arnar Rafnsson

2013-01-01

Full Text Available Leukotrienes are inflammatory and vasoactive mediators implicated in endothelium-dependent relaxations and atherosclerosis. Urinary leukotriene E4 (U-LTE4 is a validated disease marker of asthma and increases also in diabetes and acute coronary syndromes. The aim of the present study was to evaluate the association of U-LTE4 and CRP with endothelial function. Urine samples were obtained from 30 subjects (80% males; median age 65 with type 2 diabetes of at least two years duration and a median glomerular filtration rate (eGFR of 71 (14–129 mL/min. Reactive hyperemia index (RHI was used as a measure of microvascular endothelial function, whereas macrovascular endothelial function was determined be means of flow-mediated dilatation of the brachial artery (FMD. Decreased renal function was associated with lower concentrations of U-LTE4. In addition, U-LTE4 was correlated with serum creatinine (R=−0.572; P=0.001 and eGFR (R=0.517; P=0.0036. A stepwise multiple linear regression analysis identified eGFR as an independent predictor of U-LTE4 concentrations. In conclusion, the present results did not establish an association of U-LTE4 with endothelial dysfunction. However, eGFR was an independent predictor of U-LTE4, but not CRP, in this cohort, suggesting that GFR should be considered in biomarker studies of U-LTE4.

Matrix Metalloproteinases as Regulators of Vein Structure and Function: Implications in Chronic Venous Disease.

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MacColl, Elisabeth; Khalil, Raouf A

2015-12-01

Lower-extremity veins have efficient wall structure and function and competent valves that permit upward movement of deoxygenated blood toward the heart against hydrostatic venous pressure. Matrix metalloproteinases (MMPs) play an important role in maintaining vein wall structure and function. MMPs are zinc-binding endopeptidases secreted as inactive pro-MMPs by fibroblasts, vascular smooth muscle (VSM), and leukocytes. Pro-MMPs are activated by various activators including other MMPs and proteinases. MMPs cause degradation of extracellular matrix (ECM) proteins such as collagen and elastin, and could have additional effects on the endothelium, as well as VSM cell migration, proliferation, Ca(2+) signaling, and contraction. Increased lower-extremity hydrostatic venous pressure is thought to induce hypoxia-inducible factors and other MMP inducers/activators such as extracellular matrix metalloproteinase inducer, prostanoids, chymase, and hormones, leading to increased MMP expression/activity, ECM degradation, VSM relaxation, and venous dilation. Leukocyte infiltration and inflammation of the vein wall cause further increases in MMPs, vein wall dilation, valve degradation, and different clinical stages of chronic venous disease (CVD), including varicose veins (VVs). VVs are characterized by ECM imbalance, incompetent valves, venous reflux, wall dilation, and tortuosity. VVs often show increased MMP levels, but may show no change or decreased levels, depending on the VV region (atrophic regions with little ECM versus hypertrophic regions with abundant ECM) and MMP form (inactive pro-MMP versus active MMP). Management of VVs includes compression stockings, venotonics, and surgical obliteration or removal. Because these approaches do not treat the causes of VVs, alternative methods are being developed. In addition to endogenous tissue inhibitors of MMPs, synthetic MMP inhibitors have been developed, and their effects in the treatment of VVs need to be examined

Functional and Biochemical Endothelial Profiling In Vivo in a Murine Model of Endothelial Dysfunction; Comparison of Effects of 1-Methylnicotinamide and Angiotensin-converting Enzyme Inhibitor

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Bar, Anna; Olkowicz, Mariola; Tyrankiewicz, Urszula; Kus, Edyta; Jasinski, Krzysztof; Smolenski, Ryszard T.; Skorka, Tomasz; Chlopicki, Stefan

2017-01-01

Although it is known that 1-methylnicotinamide (MNA) displays vasoprotective activity in mice, as yet the effect of MNA on endothelial function has not been demonstrated in vivo. Here, using magnetic resonance imaging (MRI) we profile the effects of MNA on endothelial phenotype in mice with atherosclerosis (ApoE/LDLR-/-) in vivo, in comparison to angiotensin (Ang) -converting enzyme (ACE) inhibitor (perindopril), with known vasoprotective activity. On a biochemical level, we analyzed whether MNA- or perindopril-induced improvement in endothelial function results in changes in ACE/Ang II-ACE2/Ang-(1–7) balance, and L-arginine/asymmetric dimethylarginine (ADMA) ratio. Endothelial function and permeability were evaluated in the brachiocephalic artery (BCA) in 4-month-old ApoE/LDLR-/- mice that were non-treated or treated for 1 month or 2 months with either MNA (100 mg/kg/day) or perindopril (10 mg/kg/day). The 3D IntraGate®FLASH sequence was used for evaluation of BCA volume changes following acetylcholine (Ach) administration, and for relaxation time (T1) mapping around BCA to assess endothelial permeability using an intravascular contrast agent. Activity of ACE/Ang II and ACE2/Ang-(1–7) pathways as well as metabolites of L-arginine/ADMA pathway were measured using liquid chromatography/mass spectrometry-based methods. In non-treated 6-month-old ApoE/LDLR-/- mice, Ach induced a vasoconstriction in BCA that amounted to –7.2%. 2-month treatment with either MNA or perindopril resulted in the reversal of impaired Ach-induced response to vasodilatation (4.5 and 5.5%, respectively) and a decrease in endothelial permeability (by about 60% for MNA-, as well as perindopril-treated mice). Improvement of endothelial function by MNA and perindopril was in both cases associated with the activation of ACE2/Ang-(1–7) and the inhibition of ACE/Ang II axes as evidenced by an approximately twofold increase in Ang-(1–9) and Ang-(1–7) and a proportional decrease in Ang II

Vitamin D Receptor Activation Mitigates the Impact of Uremia on Endothelial Function in the 5/6 Nephrectomized Rats

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J. Ruth Wu-Wong

2010-01-01

Full Text Available Endothelial dysfunction increases cardiovascular disease risk in chronic kidney disease (CKD. This study investigates whether VDR activation affects endothelial function in CKD. The 5/6 nephrectomized (NX rats with experimental chronic renal insufficiency were treated with or without paricalcitol, a VDR activator. Thoracic aortic rings were precontracted with phenylephrine and then treated with acetylcholine or sodium nitroprusside. Uremia significantly affected aortic relaxation (−50.0±7.4% in NX rats versus −96.2±5.3% in SHAM at 30 M acetylcholine. The endothelial-dependent relaxation was improved to –58.2±6.0%, –77.5±7.3%, and –90.5±4.0% in NX rats treated with paricalcitol at 0.021, 0.042, and 0.083 g/kg for two weeks, respectively, while paricalcitol at 0.042 g/kg did not affect blood pressure and heart rate. Parathyroid hormone (PTH suppression alone did not improve endothelial function since cinacalcet suppressed PTH without affecting endothelial-dependent vasorelaxation. N-omega-nitro-L-arginine methyl ester completely abolished the effect of paricalcitol on improving endothelial function. These results demonstrate that VDR activation improves endothelial function in CKD.

Role of endothelial function in coronary slow-flow phenomenon with angiographically normal coronaries

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Srikanth Nathani

2016-01-01

Conclusion: Coronary slow flow phenomenon is a marker of atherosclerosis (as documented by carotid intima media thickness and our study has also shown that endothelial function is significantly impaired in patients with coronary slow flow (as documented by impaired endothelial dependent vasodilatation than that of patients with normal epicardial coronaries with normal flow.

Deterioration of endothelial function of micro- and macrocirculation in patients with diabetes type 1 and 2.

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Besic, Hana; Jeraj, Luka; Spirkoska, Ana; Jezovnik, Mateja K; Poredoš, Pavel

2017-08-01

Vascular complications are an important cause of morbidity in patients with diabetes mellitus (DM). Endothelial dysfunction is an early marker of atherosclerosis and has already been shown in macrocirculation of diabetic patients; however, data on endothelial function of microcirculation is scarce. Our aim was to evaluate endothelial function in macro- and microcirculation and their interrelationship in patients with type 1 and 2 DM. The study included 30 patients with type 1 DM, 30 patients with type 2 DM and 25 healthy controls. The endothelial function of large arteries was studied measuring flow-mediated dilation (FMD). Peripheral arterial tonometry was used for investigation of the endothelial function of microcirculation, measuring Reactive Hyperemia Index (RHI) and Augmentation Index (AI). In comparison to controls, both DM groups had decreased FMD: type 1 (4.0±5.0% vs. 10.0±7.8%, P=0.005) and type 2 (5.0±0.6% vs. 10.0±7.8%, P=0.007). However, only type 2 DM group had a lower RHI (1.71±0.44 vs. 2.05±0.54, P=0.017) in comparison to controls. Patients with type 1 and 2 DM had deteriorated functional capability of macrocirculation. However, endothelial dysfunction of microcirculation was present only in type 2 DM patients. Type 2 DM patients were also at higher risk for atherosclerosis because of the more frequent presence of risk factors.

Multiresolution analysis of pathological changes in cerebral venous dynamics in newborn mice with intracranial hemorrhage: adrenorelated vasorelaxation

International Nuclear Information System (INIS)

Pavlov, A N; Pavlova, O N; Tuchin, V V; Semyachkina-Glushkovskaya, O V; Zhang, Y; Bibikova, O A; Huang, Q; Zhu, D; Li, P; Luo, Q

2014-01-01

Intracranial hemorrhage (ICH) is the major problem of modern neonatal intensive care. Abnormalities of cerebral venous blood flow (CVBF) can play a crucial role in the development of ICH in infants. The mechanisms underlying these pathological processes remain unclear; however it has been established that the activation of the adrenorelated vasorelaxation can be an important reason. Aiming to reach a better understanding of how the adrenodependent relaxation of cerebral veins contributes to the development of ICH in newborns, we study here the effects of pharmacological stimulation of adrenorelated dilation of the sagittal sinus by isoproterenol on the cerebral venous hemodynamics. Our study is performed in newborn mice at different stages of ICH using the laser speckle contrast imaging and wavelet analysis of the vascular dynamics of CVBF. We show that the dilation of the sagittal sinus with the decreased velocity of blood flow presides to the stress-induced ICH in newborn mice. These morphofunctional vascular changes are accompanied by an increased variance of the wavelet-coefficients in the areas of endothelial and non-endothelial (K ATP -channels activity of vascular muscle) sympathetic components of the CVBF variability. Changes in the cerebral venous hemodynamics at the latent stage of ICH are associated with a high responsiveness of the sagittal sinus to isoproterenol quantifying by wavelet-coefficients related to a very slow region of the frequency domain. The obtained results certify that a high activation of the adrenergic-related vasodilatory responses to severe stress in newborn mice can be one of the important mechanisms underlying the development of ICH. Thus, the venous insufficiency with the decreased blood outflow from the brain associated with changes in the endothelial and the sympathetic components of CVBF-variability can be treated as prognostic criteria for the risk of ICH during the first days after birth. (paper)

Gas6 Promotes Inflammatory (CCR2hiCX3CR1lo) Monocyte Recruitment in Venous Thrombosis.

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Laurance, Sandrine; Bertin, François-René; Ebrahimian, Talin; Kassim, Yusra; Rys, Ryan N; Lehoux, Stéphanie; Lemarié, Catherine A; Blostein, Mark D

2017-07-01

Coagulation and inflammation are inter-related. Gas6 (growth arrest-specific 6) promotes venous thrombosis and participates to inflammation through endothelial-innate immune cell interactions. Innate immune cells can provide the initiating stimulus for venous thrombus development. We hypothesize that Gas6 promotes monocyte recruitment during venous thrombosis. Deep venous thrombosis was induced in wild-type and Gas6-deficient (-/-) mice using 5% FeCl 3 and flow reduction in the inferior vena cava. Total monocyte depletion was achieved by injection of clodronate before deep venous thrombosis. Inflammatory monocytes were depleted using an anti-C-C chemokine receptor type 2 (CCR2) antibody. Similarly, injection of an anti-chemokine ligand 2 (CCL2) antibody induced CCL2 depletion. Flow cytometry and immunofluorescence were used to characterize the monocytes recruited to the thrombus. In vivo, absence of Gas6 was associated with a reduction of monocyte recruitment in both deep venous thrombosis models. Global monocyte depletion by clodronate leads to smaller thrombi in wild-type mice. Compared with wild type, the thrombi from Gas6 -/- mice contain less inflammatory (CCR2 hi CX 3 CR1 lo ) monocytes, consistent with a Gas6-dependent recruitment of this monocyte subset. Correspondingly, selective depletion of CCR2 hi CX 3 CR1 lo monocytes reduced the formation of venous thrombi in wild-type mice demonstrating a predominant role of the inflammatory monocytes in thrombosis. In vitro, the expression of both CCR2 and CCL2 were Gas6 dependent in monocytes and endothelial cells, respectively, impacting monocyte migration. Moreover, Gas6-dependent CCL2 expression and monocyte migration were mediated via JNK (c-Jun N-terminal kinase). This study demonstrates that Gas6 specifically promotes the recruitment of inflammatory CCR2 hi CX 3 CR1 lo monocytes through the regulation of both CCR2 and CCL2 during deep venous thrombosis. © 2017 American Heart Association, Inc.

Endothelial function in children with white-coat hypertension.

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Jurko, Alexander; Jurko, Tomas; Minarik, Milan; Mestanik, Michal; Mestanikova, Andrea; Micieta, Vladimir; Visnovcova, Zuzana; Tonhajzerova, Ingrid

2018-01-29

Several studies have demonstrated endothelial dysfunction in patients with essential hypertension. However, the presence of endothelial dysfunction in children with white-coat hypertension has not been studied. We evaluated the endothelial function in children with white-coat hypertension and essential hypertension using a novel method based on the assessment of flow-mediated dilation (FMD). Study involved 106 children: 30 white-coat hypertensives (age 16.3 ± 1.3 years, mean ± SD), 30 essential hypertensives (age 16.4 ± 1.3 years), and 46 healthy controls (age 16.2 ± 1.4 years). Ultrasound scans of the right brachial artery were performed using Prosound F75 Aloka system during protocol: baseline (1 min), forearm ischemia (5 min), and post-occlusion phase (3 min). FMD (%) was expressed as a change of the arterial diameter from baseline to maximum post-occlusion value and the values coat hypertension compared to control group (p coat hypertensives compared to controls (p coat hypertension could help to elucidate the mechanisms of the increased cardiovascular risk that could be similar as found in essential hypertension; therefore, white-coat hypertension should not be considered a benign phenomenon.

Functional activities of receptors for tumor necrosis factor-alpha on human vascular endothelial cells.

NARCIS (Netherlands)

Paleolog, E.M.; Delasalle, S.A.; Buurman, W.A.; Feldmann, M.

1994-01-01

Tumor necrosis factor-alpha (TNF-alpha) plays a critical role in the control of endothelial cell function and hence in regulating traffic of circulating cells into tissues in vivo. Stimulation of endothelial cells in vitro by TNF-alpha increases the surface expression of leukocyte adhesion

Longitudinal assessment of endothelial function in the microvasculature of mice in-vivo.

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Belch, Jill J F; Akbar, Naveed; Alapati, Venkateswara; Petrie, John; Arthur, Simon; Khan, Faisel

2013-01-01

Endothelial dysfunction is associated with early development of cardiovascular disease, making longitudinal measurements desirable. We devised a protocol using laser Doppler imaging (LDI) and iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) to assess the skin microcirculation longitudinally in mice every 4 weeks for 24 weeks in two groups of C57BL/6 mice, chow versus high-cholesterol diet(known to induce endothelial dysfunction). LDI measurements were compared with vascular function (isometric tension) measured using wire myography in the tail artery in response to ACh and SNP. Microvascular responses to ACh were significantly reduced in cholesterol-fed versus chow-fed mice from week 4 onwards (Phydrochloride (L-NAME) showed a significant reduction in ACh response compared with vehicle-treated animals (P<0.05) at baseline and at 12 weeks. In cholesterol-fed mice, ACh responses were 226 ± 21 and 180 ± 21 AU (P=0.03) before and after L-NAME, respectively. A reduction in ex-vivo ACh response was detected in the tail artery in cholesterol-fed mice, and a significant correlation found between peak microvascular ACh response and maximum ACh response in the tail artery (r=0.699, P=0.017). No changes were found in SNP responses in the microvasculature or tail artery. Using this protocol, we have shown longitudinal decreases in microvascular endothelial function to cholesterol feeding. L-NAME studies confirm that the reduced vasodilatation to ACh in cholesterol-fed mice was mediated partly through reduced NO bioavailability. Wire myography of tail arteries confirmed that in-vivo measurements of microvascular function reflect ex-vivo vascular function in other beds. Longitudinal assessments of skin microvascular function in mice could provide a useful translatable model for assessing early endothelial dysfunction. Copyright © 2012 Elsevier Inc. All rights reserved.

Normal endothelial function in patients with mild-to-moderate psoriasis: a case-control study

DEFF Research Database (Denmark)

Jensen, Peter R; Zachariae, Claus; Hansen, Peter

2011-01-01

Evidence is increasing that severe psoriasis is an independent cardiovascular risk factor. Results from case-control studies of endothelial dysfunction, a marker of early atherosclerosis, in patients with moderate-to-severe psoriasis have been conflicting and were conducted with operator-dependen......Evidence is increasing that severe psoriasis is an independent cardiovascular risk factor. Results from case-control studies of endothelial dysfunction, a marker of early atherosclerosis, in patients with moderate-to-severe psoriasis have been conflicting and were conducted with operator......-dependent and technically demanding ultrasound measurement of brachial artery flow-mediated vasodilation. Therefore, we decided to measure endothelial function and other cardiovascular risk factors in patients with mild-to-moderate psoriasis (n = 30) and controls (n = 30) using a newer and relatively operator......-independent technique. No difference was detected between the groups with regards to endothelial function. However, despite the patients experiencing rather mild psoriasis they did exhibit higher levels of certain cardiovascular risk factors, including waist circumference, resting heart rate, systolic and diastolic...

Endothelial function is unaffected by changing between carvedilol and metoprolol in patients with heart failure-a randomized study

DEFF Research Database (Denmark)

Falskov, Britt; Hermann, Thomas Steffen; Raunsø, Jakob

2011-01-01

Carvedilol has been shown to be superior to metoprolol tartrate to improve clinical outcomes in patients with heart failure (HF), yet the mechanisms responsible for these differences remain unclear. We examined if there were differences in endothelial function, insulin stimulated endothelial func...... function, 24 hour ambulatory blood pressure and heart rate during treatment with carvedilol, metoprolol tartrate and metoprolol succinate in patients with HF.......Carvedilol has been shown to be superior to metoprolol tartrate to improve clinical outcomes in patients with heart failure (HF), yet the mechanisms responsible for these differences remain unclear. We examined if there were differences in endothelial function, insulin stimulated endothelial...

Flow-mediated dilation and peripheral arterial tonometry are disturbed in preeclampsia and reflect different aspects of endothelial function.

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Mannaerts, Dominique; Faes, Ellen; Goovaerts, Inge; Stoop, Tibor; Cornette, Jerome; Gyselaers, Wilfried; Spaanderman, Marc; Van Craenenbroeck, Emeline M; Jacquemyn, Yves

2017-11-01

Endothelial function and arterial stiffness are known to be altered in preeclamptic pregnancies. Previous studies have shown conflicting results regarding the best technique for assessing vascular function in pregnancy. In this study, we made a comprehensive evaluation of in vivo vascular function [including flow-mediated dilatation (FMD), peripheral arterial tonometry (PAT), and arterial stiffness] in preeclamptic patients and compared them with normal pregnancies. In addition, we assessed the relation between vascular function and systemic inflammation. Fourteen patients with preeclampsia (PE) and 14 healthy pregnant controls were included. Endothelial function was determined by FMD and PAT and arterial stiffness by carotid-femoral pulse-wave velocity and augmentation index. Systemic inflammation was assessed using mean platelet volume (MPV) and neutrophil-lymphocyte ratio (NLR). The reactive hyperemia index, assessed using PAT, is decreased at the third trimester compared with the first trimester in a normal, uncomplicated pregnancy ( P = 0.001). Arterial stiffness is significantly higher in PE versus normal pregnancy ( P function, obtained by FMD, is deteriorated in PE versus normal pregnancy ( P = 0.015), whereas endothelial function assessment by PAT is improved in PE versus normal pregnancy ( P = 0.001). Systemic inflammation (MPV and NLR) increases during normal pregnancy. FMD and PAT are disturbed in PE. Endothelial function, assessed by FMD and PAT, shows distinct results. This may indicate that measurements with FMD and PAT reflect different aspects of endothelial function and that PAT should not be used as a substitute for FMD as a measure of endothelial function in pregnancy. Copyright © 2017 the American Physiological Society.

Geraniol improves endothelial function by inhibiting NOX-2 derived oxidative stress in high fat diet fed mice

International Nuclear Information System (INIS)

Wang, Xiaoyu; Zhao, Shiqi; Su, Mengqi; Sun, Li; Zhang, Song; Wang, Dingyu; Liu, Zhaorui; Yuan, Yue; Liu, Yang; Li, Yue

2016-01-01

Endothelial dysfunction occurs in obese patients and high-fat diet (HFD) fed experimental animals. While geraniol has been reported to ameliorate inflammation and oxidative stress, inhibit tumor cell proliferation, and improve atherosclerosis, its direct effect on endothelial function remains uncharacterized. The present study therefore investigated the effect of geraniol on endothelial function in HFD mice and its underlying mechanisms. C57 BL/6 mice were fed an HFD (n = 40) or a normal diet (n = 20) for 8 weeks. HFD fed mice then were randomized to intraperitoneal treatment with geraniol (n = 20) or vehicle (n = 20) for another 6 weeks. Acetylcholine (Ach)-induced endothelial dependent vasorelaxation was measured on wire myography; reactive oxygen species (ROS) generation was assessed by fluorescence imaging, and NADPH oxidases (NOXs) and adhesive molecules VCAM-1 and ICAM-1 protein expression by western blotting. Geraniol improved endothelial function in HFD fed mice, as evidenced by its: 1. restoring endothelial dependent vasorelaxation induced by Ach, and reversing increased VCAM-1 and ICAM-1 expression; 2. attenuating HFD induced increased serum TBARS and aortic ROS generation; and 3. downregulating aortic NOX-2 expression in both HFD fed mice and in palmitic acid treated endothelial cells. Geraniol therefore protects against endothelial dysfunction induced by HFD through reducing NOX-2 associated ROS generation. -- Highlights: •Geraniol improved endothelial dependent relaxation in high fat diet fed mice. •Geraniol alleviated vascular injury in high fat diet fed mice. •Geraniol inhibited ROS generation through downregulating NOX-2 expression.

Geraniol improves endothelial function by inhibiting NOX-2 derived oxidative stress in high fat diet fed mice

Energy Technology Data Exchange (ETDEWEB)

Wang, Xiaoyu; Zhao, Shiqi; Su, Mengqi; Sun, Li; Zhang, Song; Wang, Dingyu; Liu, Zhaorui; Yuan, Yue; Liu, Yang [Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province (China); Li, Yue, E-mail: ly99ly@vip.163.com [Department of Cardiology, the First Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province (China); Key Laboratory of Cardiac Diseases and Heart Failure, Harbin Medical University, Harbin, 150001, Heilongjiang Province (China)

2016-05-20

Endothelial dysfunction occurs in obese patients and high-fat diet (HFD) fed experimental animals. While geraniol has been reported to ameliorate inflammation and oxidative stress, inhibit tumor cell proliferation, and improve atherosclerosis, its direct effect on endothelial function remains uncharacterized. The present study therefore investigated the effect of geraniol on endothelial function in HFD mice and its underlying mechanisms. C57 BL/6 mice were fed an HFD (n = 40) or a normal diet (n = 20) for 8 weeks. HFD fed mice then were randomized to intraperitoneal treatment with geraniol (n = 20) or vehicle (n = 20) for another 6 weeks. Acetylcholine (Ach)-induced endothelial dependent vasorelaxation was measured on wire myography; reactive oxygen species (ROS) generation was assessed by fluorescence imaging, and NADPH oxidases (NOXs) and adhesive molecules VCAM-1 and ICAM-1 protein expression by western blotting. Geraniol improved endothelial function in HFD fed mice, as evidenced by its: 1. restoring endothelial dependent vasorelaxation induced by Ach, and reversing increased VCAM-1 and ICAM-1 expression; 2. attenuating HFD induced increased serum TBARS and aortic ROS generation; and 3. downregulating aortic NOX-2 expression in both HFD fed mice and in palmitic acid treated endothelial cells. Geraniol therefore protects against endothelial dysfunction induced by HFD through reducing NOX-2 associated ROS generation. -- Highlights: •Geraniol improved endothelial dependent relaxation in high fat diet fed mice. •Geraniol alleviated vascular injury in high fat diet fed mice. •Geraniol inhibited ROS generation through downregulating NOX-2 expression.

Hyperuricemia in Destabilization of Endothelial Function in Adolescents with Arterial Hypertension

Directory of Open Access Journals (Sweden)

N.M. Korenev

2013-08-01

Full Text Available The objective of this work was to study the correlation of uric acid level in blood serum and parameters of endothelial function and non-specific inflammation in adolescents with arterial hypertension considering their body weight. In the most of patients with arterial hypertension endothelial dysfunction was detected; endothelium-dependent vasodilation was more altered in the patients with obesity and especially in those with hyperuricemia. An increase in C-reactive protein serum level was mainly associated with obesity; a decrease in systolic-diastolic ratio — with hyperuricemia.

Gestational diabetes, preeclampsia and cytokine release: similarities and differences in endothelial cell function.

Science.gov (United States)

Rao, Rashmi; Sen, Suvajit; Han, Bing; Ramadoss, Sivakumar; Chaudhuri, Gautam

2014-01-01

Gestational diabetes, pre-eclampsia as well as intra-uterine infection during pregnancy affects the function of the endothelium both in the mother and the fetus leading to endothelial dysfunction. Gestational diabetes is also associated with an increased incidence of pre-eclampsia and it is likely that both the hyperglycemia as well as the release of cytokines especially TNFα during hyperglycemia may play an important role in the pathogenesis of endothelial dysfunction leading to preeclampsia. Similarly, some but not all studies have suggested that infection of the mother under certain circumstances can also lead to preeclampsia as women with either a bacterial or viral infection were at a higher risk of developing preeclampsia, compared to women without infection and infection also leads to a release in TNFα. Endothelial cells exposed to either high glucose or TNFα leads to an increase in the production of H2O2 and to a decrease in endothelial cell proliferation. The cellular and molecular mechanisms involved in this phenomenon are discussed.Gestational diabetes, pre-eclampsia as well as intra-uterine infection during pregnancy has profound effects on the fetus and long term effects on the neonate. All three conditions affect the function of the endothelium both in the mother and the fetus leading to endothelial dysfunction. Gestational diabetes is also associated with an increased incidence of pre-eclampsia and it is likely that both the hyperglycemia as well as the release of cytokines especially TNFα during hyperglycemia may play an important role in the pathogenesis of endothelial dysfunction leading to preeclampsia. It has also been suggested although not universally accepted that under certain circumstances maternal infection may also predispose to pre-eclampsia. Pre-eclampsia is also associated with the release of TNFα and endothelial dysfunction. However, the cellular and molecular mechanism(s) leading to the endothelial dysfunction by either

Effects of α-lipoic acid on endothelial function in aged diabetic and high-fat fed rats

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Sena, C M; Nunes, E; Louro, T; Proença, T; Fernandes, R; Boarder, M R; Seiça, R M

2007-01-01

Background and purpose: This study was conducted to investigate the effects of α-lipoic acid (α-LA) on endothelial function in diabetic and high-fat fed animal models and elucidate the potential mechanism underlying the benefits of α-LA. Experimental approach: Plasma metabolites reflecting glucose and lipid metabolism, endothelial function, urinary albumin excretion (UAE), plasma and aortic malondialdehyde (MDA) and urinary 8-hydroxydeoxyguanosine (8-OHdG) were assessed in non-diabetic controls (Wistar rats), untreated Goto-Kakizaki (GK) diabetic and high-fat fed GK rats (fed with atherogenic diet only, treated with α-LA and treated with vehicle, for 3 months). Vascular eNOS, nitrotyrosine, carbonyl groups and superoxide anion were also assessed in the different groups. Key results: α-LA and soybean oil significantly reduced both total and non-HDL serum cholesterol and triglycerides induced by atherogenic diet. MDA, carbonyl groups, vascular superoxide and 8-OHdG levels were higher in GK and high-fat fed GK groups and fully reversed with α-LA treatment. High-fat fed GK diabetic rats showed significantly reduced endothelial function and increased UAE, effects ameliorated with α-LA. This endothelial dysfunction was associated with decreased NO production, decreased expression of eNOS and increased vascular superoxide production and nitrotyrosine expression. Conclusions and implications: α-LA restores endothelial function and significantly improves systemic and local oxidative stress in high-fat fed GK diabetic rats. Improved endothelial function due to α-LA was at least partially attributed to recoupling of eNOS and increased NO bioavailability and represents a pharmacological approach to prevent major complications associated with type 2 diabetes. PMID:17906683

The anti-hypercholesterolemic effect of low p53 expression protects vascular endothelial function in mice.

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Francois Leblond

Full Text Available To demonstrate that p53 modulates endothelial function and the stress response to a high-fat western diet (WD.Three-month old p53+/+ wild type (WT and p53+/- male mice were fed a regular or WD for 3 months. Plasma levels of total cholesterol (TC and LDL-cholesterol were significantly elevated (p<0.05 in WD-fed WT (from 2.1±0.2 mmol/L to 3.1±0.2, and from 0.64±0.09 mmol/L to 1.25±0.11, respectively but not in p53+/- mice. The lack of cholesterol accumulation in WD-fed p53+/- mice was associated with high bile acid plasma concentrations (p53+/- =  4.7±0.9 vs. WT =  3.3±0.2 μmol/L, p<0.05 concomitant with an increased hepatic 7-alpha-hydroxylase mRNA expression. While the WD did not affect aortic endothelial relaxant function in p53+/- mice (WD =  83±5 and RD =  82±4% relaxation, it increased the maximal response to acetylcholine in WT mice (WD =  87±2 vs. RD =  62±5% relaxation, p<0.05 to levels of p53+/-. In WT mice, the rise in TC associated with higher (p<0.05 plasma levels of pro-inflammatory keratinocyte-derived chemokine, and an over-activation (p<0.05 of the relaxant non-nitric oxide/non-prostacyclin endothelial pathway. It is likely that in WT mice, activations of these pathways are adaptive and contributed to maintain endothelial function, while the WD neither promoted inflammation nor affected endothelial function in p53+/- mice.Our data demonstrate that low endogenous p53 expression prevents the rise in circulating levels of cholesterol when fed a WD. Consequently, the endothelial stress of hypercholesterolemia is absent in young p53+/- mice as evidenced by the absence of endothelial adaptive pathway over-activation to minimize stress-related damage.

Renin-Angiotensin System Blockade Associated with Statin Improves Endothelial Function in Diabetics

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Ronaldo Altenburg Gismondi

2015-01-01

Full Text Available AbstractBackground:Studies suggest that statins have pleiotropic effects, such as reduction in blood pressure, and improvement in endothelial function and vascular stiffness.Objective:To analyze if prior statin use influences the effect of renin-angiotensin-aldosterone system inhibitors on blood pressure, endothelial function, and vascular stiffness.Methods:Patients with diabetes and hypertension with office systolic blood pressure ≥ 130 mmHg and/or diastolic blood pressure ≥ 80 mmHg had their antihypertensive medications replaced by amlodipine during 6 weeks. They were then randomized to either benazepril or losartan for 12 additional weeks while continuing on amlodipine. Blood pressure (assessed with ambulatory blood pressure monitoring, endothelial function (brachial artery flow-mediated dilation, and vascular stiffness (pulse wave velocity were evaluated before and after the combined treatment. In this study, a post hoc analysis was performed to compare patients who were or were not on statins (SU and NSU groups, respectively.Results:The SU group presented a greater reduction in the 24-hour systolic blood pressure (from 134 to 122 mmHg, p = 0.007, and in the brachial artery flow-mediated dilation (from 6.5 to 10.9%, p = 0.003 when compared with the NSU group (from 137 to 128 mmHg, p = 0.362, and from 7.5 to 8.3%, p = 0.820. There was no statistically significant difference in pulse wave velocity (SU group: from 9.95 to 9.90 m/s, p = 0.650; NSU group: from 10.65 to 11.05 m/s, p = 0.586.Conclusion:Combined use of statins, amlodipine, and renin-angiotensin-aldosterone system inhibitors improves the antihypertensive response and endothelial function in patients with hypertension and diabetes.

Bone Morphogenic Protein 4-Smad-Induced Upregulation of Platelet-Derived Growth Factor AA Impairs Endothelial Function.

Science.gov (United States)

Hu, Weining; Zhang, Yang; Wang, Li; Lau, Chi Wai; Xu, Jian; Luo, Jiang-Yun; Gou, Lingshan; Yao, Xiaoqiang; Chen, Zhen-Yu; Ma, Ronald Ching Wan; Tian, Xiao Yu; Huang, Yu

2016-03-01

Bone morphogenic protein 4 (BMP4) is an important mediator of endothelial dysfunction in cardio-metabolic diseases, whereas platelet-derived growth factors (PDGFs) are major angiogenic and proinflammatory mediator, although the functional link between these 2 factors is unknown. The present study investigated whether PDGF mediates BMP4-induced endothelial dysfunction in diabetes mellitus. We generated Ad-Bmp4 to overexpress Bmp4 and Ad-Pdgfa-shRNA to knockdown Pdgfa in mice through tail intravenous injection. SMAD4-shRNA lentivirus, SMAD1-shRNA, and SMAD5 shRNA adenovirus were used for knockdown in human and mouse endothelial cells. We found that PDGF-AA impaired endothelium-dependent vasodilation in aortas and mesenteric resistance arteries. BMP4 upregulated PDGF-AA in human and mouse endothelial cells, which was abolished by BMP4 antagonist noggin or knockdown of SMAD1/5 or SMAD4. BMP4-impared relaxation in mouse aorta was also ameliorated by PDGF-AA neutralizing antibody. Tail injection of Ad-Pdgfa-shRNA ameliorates endothelial dysfunction induced by Bmp4 overexpression (Ad-Bmp4) in vivo. Serum PDGF-AA was elevated in both diabetic patients and diabetic db/db mice compared with nondiabetic controls. Pdgfa-shRNA or Bmp4-shRNA adenovirus reduced serum PDGF-AA concentration in db/db mice. PDGF-AA neutralizing antibody or tail injection with Pdgfa-shRNA adenovirus improved endothelial function in aortas and mesenteric resistance arteries from db/db mice. The effect of PDGF-AA on endothelial function in mouse aorta was also inhibited by Ad-Pdgfra-shRNA to inhibit PDGFRα. The present study provides novel evidences to show that PDGF-AA impairs endothelium-dependent vasodilation and PDGF-AA mediates BMP4-induced adverse effect on endothelial cell function through SMAD1/5- and SMAD4-dependent mechanisms. Inhibition of PGDF-AA ameliorates vascular dysfunction in diabetic mice. © 2016 American Heart Association, Inc.

Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease

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Nyström, Thomas; Gutniak, Mark K; Zhang, Qimin

2004-01-01

GLP-1 stimulates insulin secretion, suppresses glucagon secretion, delays gastric emptying, and inhibits small bowel motility, all actions contributing to the anti-diabetogenic peptide effect. Endothelial dysfunction is strongly associated with insulin resistance and type 2 diabetes mellitus...... and may cause the angiopathy typifying this debilitating disease. Therefore, interventions affecting both endothelial dysfunction and insulin resistance may prove useful in improving survival in type 2 diabetes patients. We investigated GLP-1's effect on endothelial function and insulin sensitivity (S......(I)) in two groups: 1) 12 type 2 diabetes patients with stable coronary artery disease and 2) 10 healthy subjects with normal endothelial function and S(I). Subjects underwent infusion of recombinant GLP-1 or saline in a random crossover study. Endothelial function was measured by postischemic FMD of brachial...

Endothelial dysfunction after non-cardiac surgery

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Søndergaard, E S; Fonnes, S; Gögenur, I

2015-01-01

was to systematically review the literature to evaluate the association between non-cardiac surgery and non-invasive markers of endothelial function. METHODS: A systematic search was conducted in MEDLINE, EMBASE and Cochrane Library Database according to the PRISMA guidelines. Endothelial dysfunction was described only...... transplantation and vascular surgery respectively) had an improvement in endothelial dysfunction 1 month after surgery. CONCLUSION: Endothelial function changes in relation to surgery. Assessment of endothelial function by non-invasive measures has the potential to guide clinicians in the prevention or treatment...

Venous and autonomic function in formerly pre-eclamptic women and BMI-matched controls.

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Heidema, Wieteke M; van Drongelen, Joris; Spaanderman, Marc E A; Scholten, Ralph R

2018-03-25

Pre-pregnancy reduced plasma volume increases the risk on subsequent pre-eclamptic pregnancy. Reduced plasma volume is thought to reflect venous reserve capacity, especially when venous vasculature is constricted and sympathetic tone is elevated. As obesity might affect these variables and also relates to pre-eclampsia, increased body weight may underlie these observations. We hypothesized that the relationship between reduced venous reserve and preeclampsia is independent of body mass index (BMI). We compared the non-pregnant venous reserve capacity in 30 formerly pre-eclamptic women, equally divided in 3 BMI-classes (BMI 19.5-24.9, BMI 25-29.9, BMI ≥30) to 30 controls. Cases and controls were matched for BMI, age and parity. The venous reserve capacity was quantified by assessing plasma volume and venous compliance. The autonomic nervous system regulating the venous capacitance was evaluated with heart rate variability analysis in resting supine position and during positive head-up tilt (HUT). Formerly pre-eclamptic women had in supine position lower plasma volume than controls (1339 ± 79 vs 1547 ± 139 ml/m 2 (pBMI-matched controls, reduced venous reserve capacity. This is reflected by lower plasma volume and venous compliance, the autonomic balance is shifted towards sympathetic dominance and lower baroreceptor sensitivity. This suggests that not BMI, but underlying reduced venous reserve relates to pre-eclampsia. This article is protected by copyright. All rights reserved.

Effect of acute hypobaric hypoxia on the endothelial glycocalyx and digital reactive hyperemia in humans

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Johansson, Pär I; Bergström, Anita; Aachmann-Andersen, Niels Jacob

2014-01-01

INTRODUCTION: Hypoxia is associated with increased capillary permeability. This study tested whether acute hypobaric hypoxia involves degradation of the endothelial glycocalyx. METHODS: We exposed 12 subjects to acute hypobaric hypoxia (equivalent to 4500 m for 2-4 h) and measured venous blood...

Muscle sympathetic nerve activity is related to a surrogate marker of endothelial function in healthy individuals.

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Yrsa Bergmann Sverrisdóttir

Full Text Available BACKGROUND: Evidence from animal studies indicates the importance of an interaction between the sympathetic nervous system and the endothelium for cardiovascular regulation. However the interaction between these two systems remains largely unexplored in humans. The aim of this study was to investigate whether directly recorded sympathetic vasoconstrictor outflow is related to a surrogate marker of endothelial function in healthy individuals. METHODS AND RESULTS: In 10 healthy normotensive subjects (3 f/7 m, (age 37+/-11 yrs, (BMI 24+/-3 kg/m(2 direct recordings of sympathetic action potentials to the muscle vascular bed (MSNA were performed and endothelial function estimated with the Reactive Hyperaemia- Peripheral Arterial Tonometry (RH-PAT technique. Blood samples were taken and time spent on leisure-time physical activities was estimated. In all subjects the rate between resting flow and the maximum flow, the Reactive Hyperemic index (RH-PAT index, was within the normal range (1.9-3.3 and MSNA was as expected for age and gender (13-44 burst/minute. RH-PAT index was inversely related to MSNA (r = -0.8, p = 0.005. RH-PAT index and MSNA were reciprocally related to time (h/week spent on physical activity (p = 0.005 and p = 0.006 respectively and platelet concentration (PLT (p = 0.02 and p = 0.004 respectively. CONCLUSIONS: Our results show that sympathetic nerve activity is related to a surrogate marker of endothelial function in healthy normotensive individuals, indicating that sympathetic outflow may be modulated by changes in endothelial function. In this study time spent on physical activity is identified as a predictor of sympathetic nerve activity and endothelial function in a group of healthy individuals. The results are of importance in understanding mechanisms underlying sympathetic activation in conditions associated with endothelial dysfunction and emphasise the importance of a daily exercise routine for maintenance of cardiovascular

EFFECT OF HIGH-INTENSITY EXERCISE ON ENDOTHELIAL FUNCTION IN PATIENTS WITH T2DM

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Carlos Alberto da Silva

2016-04-01

Full Text Available Introduction: Diabetes mellitus is the most common metabolic disease worldwide. Endothelial dysfunction characteristic of these patients is one of the major risk factors for atherosclerosis. Early diagnosis of endothelial dysfunction is essential for the treatment especially of non-invasive manner, such as flow mediated dilation. Physical exercise is capable of generating beneficial adaptations may improve endothelial function. Objective: Identify the effect of physical exercise, using the clinical technique of ultrasound in the assessment of the endothelial function of patients with metabolic syndrome or type 2 diabetes mellitus. Methods: Thirty-one patients with type 2 diabetes mellitus or metabolic syndrome were studied, with a mean age (± SD of 58±6 years, randomized into three groups. The training was performed for 50 minutes, four times a week. Before and after six weeks of training, subjects performed the endurance test and a study of the endothelial function of the brachial artery by high-resolution ultrasound. Results: After hyperemia, the percentage of arterial diameter was significantly higher for the high-intensity group (HI before = 2.52±2.85mm and after = 31.81±12.21mm; LI before = 3.23±3.52mm and after = 20.61±7.76mm; controls before = 3.56±2.33mm and after = 2.43±2.14mm; p<0.05. Conclusions: The high-intensity aerobic training improved the vasodilatation response-dependent endothelium, recorded by ultrasound, in patients with metabolic syndrome and type 2 diabetes.

Abl family kinases regulate endothelial barrier function in vitro and in mice.

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Elizabeth M Chislock

Full Text Available The maintenance of endothelial barrier function is essential for normal physiology, and increased vascular permeability is a feature of a wide variety of pathological conditions, leading to complications including edema and tissue damage. Use of the pharmacological inhibitor imatinib, which targets the Abl family of non-receptor tyrosine kinases (Abl and Arg, as well as other tyrosine kinases including the platelet-derived growth factor receptor (PDGFR, Kit, colony stimulating factor 1 receptor (CSF1R, and discoidin domain receptors, has shown protective effects in animal models of inflammation, sepsis, and other pathologies characterized by enhanced vascular permeability. However, the imatinib targets involved in modulation of vascular permeability have not been well-characterized, as imatinib inhibits multiple tyrosine kinases not only in endothelial cells and pericytes but also immune cells important for disorders associated with pathological inflammation and abnormal vascular permeability. In this work we employ endothelial Abl knockout mice to show for the first time a direct role for Abl in the regulation of vascular permeability in vivo. Using both Abl/Arg-specific pharmacological inhibition and endothelial Abl knockout mice, we demonstrate a requirement for Abl kinase activity in the induction of endothelial permeability by vascular endothelial growth factor both in vitro and in vivo. Notably, Abl kinase inhibition also impaired endothelial permeability in response to the inflammatory mediators thrombin and histamine. Mechanistically, we show that loss of Abl kinase activity was accompanied by activation of the barrier-stabilizing GTPases Rac1 and Rap1, as well as inhibition of agonist-induced Ca(2+ mobilization and generation of acto-myosin contractility. In all, these findings suggest that pharmacological targeting of the Abl kinases may be capable of inhibiting endothelial permeability induced by a broad range of agonists and that use

A Cell Culture Approach to Optimized Human Corneal Endothelial Cell Function

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Bartakova, Alena; Kuzmenko, Olga; Alvarez-Delfin, Karen; Kunzevitzky, Noelia J.; Goldberg, Jeffrey L.

2018-01-01

Purpose Cell-based therapies to replace corneal endothelium depend on culture methods to optimize human corneal endothelial cell (HCEC) function and minimize endothelial-mesenchymal transition (EnMT). Here we explore contribution of low-mitogenic media on stabilization of phenotypes in vitro that mimic those of HCECs in vivo. Methods HCECs were isolated from cadaveric donor corneas and expanded in vitro, comparing continuous presence of exogenous growth factors (“proliferative media”) to media without those factors (“stabilizing media”). Identity based on canonical morphology and expression of surface marker CD56, and function based on formation of tight junction barriers measured by trans-endothelial electrical resistance assays (TEER) were assessed. Results Primary HCECs cultured in proliferative media underwent EnMT after three to four passages, becoming increasingly fibroblastic. Stabilizing the cells before each passage by switching them to a media low in mitogenic growth factors and serum preserved canonical morphology and yielded a higher number of cells. HCECs cultured in stabilizing media increased both expression of the identity marker CD56 and also tight junction monolayer integrity compared to cells cultured without stabilization. Conclusions HCECs isolated from donor corneas and expanded in vitro with a low-mitogenic media stabilizing step before each passage demonstrate more canonical structural and functional features and defer EnMT, increasing the number of passages and total canonical cell yield. This approach may facilitate development of HCEC-based cell therapies. PMID:29625488

A Unique Case of Acute Cerebral Venous Sinus Thrombosis Secondary to Primary Varicella Zoster Virus Infection.

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Imam, Syed F; Lodhi, Omair Ul Haq; Fatima, Zainab; Nasim, Saneeya; Malik, Waseem T; Saleem, Muhammad Sabih

2017-09-16

Primary varicella zoster virus (VZV) infection, predominantly in the pediatric population, presents with pyrexia and a classic pruritic vesicular rash. In adults, although less common, it is more severe and linked to more complications. Neurological complications, which account for less than 1% of all VZV complications, include meningitis, encephalitis, arterial vasculopathy, and venous thrombosis. We present a case of a 39-year-old male who developed extensive cerebral venous sinus thrombosis following primary VZV infection. Venous thrombosis in VZV has been suggested to be caused by autoantibodies against protein S, pre-existing hypercoagulability, or endothelial damage. The patient was acutely managed using intravenous acyclovir and heparin. Long-term anticoagulation therapy with warfarin was continued after discharge. We concluded that clinicians should be aware of the rare complications of this common pathology so that a timely diagnosis can be made, followed by prompt management. Further studies need to be done to better understand acute cerebral venous sinus thrombosis secondary to VZV.

Hormonal regulation of Na+/K+-dependent ATPase activity and pump function in corneal endothelial cells.

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Hatou, Shin

2011-10-01

Na- and K-dependent ATPase (Na,K-ATPase) in the basolateral membrane of corneal endothelial cells plays an important role in the pump function of the corneal endothelium. We investigated the role of dexamethasone in the regulation of Na,K-ATPase activity and pump function in these cells. Mouse corneal endothelial cells were exposed to dexamethasone or insulin. ATPase activity was evaluated by spectrophotometric measurement, and pump function was measured using an Ussing chamber. Western blotting and immunocytochemistry were performed to measure the expression of the Na,K-ATPase α1-subunit. Dexamethasone increased Na,K-ATPase activity and the pump function of endothelial cells. Western blot analysis indicated that dexamethasone increased the expression of the Na,K-ATPase α1-subunit but decreased the ratio of active to inactive Na,K-ATPase α1-subunit. Insulin increased Na,K-ATPase activity and pump function of cultured corneal endothelial cells. These effects were transient and blocked by protein kinase C inhibitors and inhibitors of protein phosphatases 1 (PP1) and 2A (PP2A). Western blot analysis indicated that insulin decreased the amount of inactive Na,K-ATPase α1-subunit, but the expression of total Na,K-ATPase α1-subunit was unchanged. Immunocytochemistry showed that insulin increased cell surface expression of the Na,K-ATPase α1-subunit. Our results suggest that dexamethasone and insulin stimulate Na,K-ATPase activity in mouse corneal endothelial cells. The effect of dexamethasone activation in these cells was mediated by Na,K-ATPase synthesis and an increased enzymatic activity because of dephosphorylation of Na,K-ATPase α1-subunits. The effect of insulin is mediated by the protein kinase C, PP1, and/or PP2A pathways.

Role of folic acid in nitric oxide bioavailability and vascular endothelial function.

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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.

Chronic administration of the probiotic kefir improves the endothelial function in spontaneously hypertensive rats.

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Friques, Andreia G F; Arpini, Clarisse M; Kalil, Ieda C; Gava, Agata L; Leal, Marcos A; Porto, Marcella L; Nogueira, Breno V; Dias, Ananda T; Andrade, Tadeu U; Pereira, Thiago Melo C; Meyrelles, Silvana S; Campagnaro, Bianca P; Vasquez, Elisardo C

2015-12-30

The beverage obtained by fermentation of milk with kefir grains, a complex matrix containing acid bacteria and yeasts, has been shown to have beneficial effects in various diseases. However, its effects on hypertension and endothelial dysfunction are not yet clear. In this study, we evaluated the effects of kefir on endothelial cells and vascular responsiveness in spontaneously hypertensive rats (SHR). SHR were treated with kefir (0.3 mL/100 g body weight) for 7, 15, 30 and 60 days and compared with non-treated SHR and with normotensive Wistar-Kyoto rats. Vascular endothelial function was evaluated in aortic rings through the relaxation response to acetylcholine (ACh). The balance between reactive oxygen species (ROS) and nitric oxide (NO) synthase was evaluated through specific blockers in the ACh-induced responses and through flow cytometry in vascular tissue. Significant effects of kefir were observed only after treatment for 60 days. The high blood pressure and tachycardia exhibited by the SHR were attenuated by approximately 15 % in the SHR-kefir group. The impaired ACh-induced relaxation of the aortic rings observed in the SHR (37 ± 4 %, compared to the Wistar rats: 74 ± 5 %), was significantly attenuated in the SHR group chronically treated with kefir (52 ± 4 %). The difference in the area under the curve between before and after the NADPH oxidase blockade or NO synthase blockade of aortic rings from SHR were of approximately +90 and -60 %, respectively, when compared with Wistar rats. In the aortic rings from the SHR-kefir group, these values were reduced to +50 and -40 %, respectively. Flow cytometric analysis of aortic endothelial cells revealed increased ROS production and decreased NO bioavailability in the SHR, which were significantly attenuated by the treatment with kefir. Scanning electronic microscopy showed vascular endothelial surface injury in SHR, which was partially protected following administration of kefir for 60 days. In addition, the

Citrus Polyphenol Hesperidin Stimulates Production of Nitric Oxide in Endothelial Cells while Improving Endothelial Function and Reducing Inflammatory Markers in Patients with Metabolic Syndrome

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Rizza, Stefano; Muniyappa, Ranganath; Iantorno, Micaela; Kim, Jeong-a; Chen, Hui; Pullikotil, Philomena; Senese, Nicoletta; Tesauro, Manfredi; Lauro, Davide; Cardillo, Carmine

2011-01-01

Context: Hesperidin, a citrus flavonoid, and its metabolite hesperetin may have vascular actions relevant to their health benefits. Molecular and physiological mechanisms of hesperetin actions are unknown. Objective: We tested whether hesperetin stimulates production of nitric oxide (NO) from vascular endothelium and evaluated endothelial function in subjects with metabolic syndrome on oral hesperidin therapy. Design, Setting, and Interventions: Cellular mechanisms of action of hesperetin were evaluated in bovine aortic endothelial cells (BAEC) in primary culture. A randomized, placebo-controlled, double-blind, crossover trial examined whether oral hesperidin administration (500 mg once daily for 3 wk) improves endothelial function in individuals with metabolic syndrome (n = 24). Main Outcome Measure: We measured the difference in brachial artery flow-mediated dilation between placebo and hesperidin treatment periods. Results: Treatment of BAEC with hesperetin acutely stimulated phosphorylation of Src, Akt, AMP kinase, and endothelial NO synthase to produce NO; this required generation of H2O2. Increased adhesion of monocytes to BAEC and expression of vascular cell adhesion molecule-1 in response to TNF-α treatment was reduced by pretreatment with hesperetin. In the clinical study, when compared with placebo, hesperidin treatment increased flow-mediated dilation (10.26 ± 1.19 vs. 7.78 ± 0.76%; P = 0.02) and reduced concentrations of circulating inflammatory biomarkers (high-sensitivity C-reactive protein, serum amyloid A protein, soluble E-selectin). Conclusions: Novel mechanisms for hesperetin action in endothelial cells inform effects of oral hesperidin treatment to improve endothelial dysfunction and reduce circulating markers of inflammation in our exploratory clinical trial. Hesperetin has vasculoprotective actions that may explain beneficial cardiovascular effects of citrus consumption. PMID:21346065

Consumption of High-Polyphenol Dark Chocolate Improves Endothelial Function in Individuals with Stage 1 Hypertension and Excess Body Weight

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Lívia de Paula Nogueira

2012-01-01

Full Text Available Background. Hypertension and excess body weight are important risk factors for endothelial dysfunction. Recent evidence suggests that high-polyphenol dark chocolate improves endothelial function and lowers blood pressure. This study aimed to evaluate the association of chocolate 70% cocoa intake with metabolic profile, oxidative stress, inflammation, blood pressure, and endothelial function in stage 1 hypertensives with excess body weight. Methods. Intervention clinical trial includes 22 stage 1 hypertensives without previous antihypertensive treatment, aged 18 to 60 years and presents a body mass index between 25.0 and 34.9 kg/m2. All participants were instructed to consume 50 g of chocolate 70% cocoa/day (2135 mg polyphenols for 4 weeks. Endothelial function was evaluated by peripheral artery tonometry using Endo-PAT 2000 (Itamar Medical. Results. Twenty participants (10 men completed the study. Comparison of pre-post intervention revealed that (1 there were no significant changes in anthropometric parameters, percentage body fat, glucose metabolism, lipid profile, biomarkers of inflammation, adhesion molecules, oxidized LDL, and blood pressure; (2 the assessment of endothelial function through the reactive hyperemia index showed a significant increase: 1.94 ± 0.18 to 2.22 ± 0.08, P=0.01. Conclusion.In individuals with stage 1 hypertension and excess body weight, high-polyphenol dark chocolate improves endothelial function.

Dynamic Contrast-Enhanced Perfusion MRI of High Grade Brain Gliomas Obtained with Arterial or Venous Waveform Input Function.

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Filice, Silvano; Crisi, Girolamo

2016-01-01

The aim of this study was to evaluate the differences in dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) perfusion estimates of high-grade brain gliomas (HGG) due to the use of an input function (IF) obtained respectively from arterial (AIF) and venous (VIF) approaches by two different commercially available software applications. This prospective study includes 20 patients with pathologically confirmed diagnosis of high-grade gliomas. The data source was processed by using two DCE dedicated commercial packages, both based on the extended Toft model, but the first customized to obtain input function from arterial measurement and the second from sagittal sinus sampling. The quantitative parametric perfusion maps estimated from the two software packages were compared by means of a region of interest (ROI) analysis. The resulting input functions from venous and arterial data were also compared. No significant difference has been found between the perfusion parameters obtained with the two different software packages (P-value < .05). The comparison of the VIFs and AIFs obtained by the two packages showed no statistical differences. Direct comparison of DCE-MRI measurements with IF generated by means of arterial or venous waveform led to no statistical difference in quantitative metrics for evaluating HGG. However, additional research involving DCE-MRI acquisition protocols and post-processing would be beneficial to further substantiate the effectiveness of venous approach as the IF method compared with arterial-based IF measurement. Copyright © 2015 by the American Society of Neuroimaging.

Acetylcholine versus cold pressor testing for evaluation of coronary endothelial function.

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Ahmed AlBadri

Full Text Available Assessment of coronary endothelial function with intracoronary acetylcholine (IC-Ach provides diagnostic and prognostic data in patients with suspected coronary microvascular dysfunction (CMD, but is often not feasible due in part to the time and expertise needed for pharmacologic mixing. Cold pressor testing (CPT is a simple and safe stimulus useful for either invasive or non-invasive endothelial function testing and myocardial perfusion imaging but has not been specifically evaluated among symptomatic women with signs of ischemic heart disease (IHD who have no obstructive coronary artery disease (CAD.163 women with signs and symptoms of IHD and no obstructive CAD from the NHLBI- Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD study underwent coronary reactivity testing with a Doppler flow wire (FloWire® Volcano, San Diego, CA in the proximal left anterior descending artery. Coronary artery diameter and coronary blood flow (CBF assessed by core lab using QCA before and after IC-Ach (18.2 μg/ml infused over 3 minutes and during CPT.Mean age was 55 ± 12 years. Rate pressure product (RPP in response to IC-Ach did not change (baseline to peak, P = 0.26, but increased during CPT (363±1457; P = 0.0028. CBF in response to CPT was poorly correlated to IC-Ach CBF. Change in coronary artery diameter after IC-Ach correlated with change after CPT (r = 0.59, P<0.001. The correlation coefficient was stronger in subjects with coronary dilation to IC-Ach (r = 0.628, P<0.001 versus those without dilation (r = 0.353, P = 0.002, suggesting that other factors may be important to this relationship when endothelium is abnormal.In women with no obstructive CAD and suspected CMD, coronary diameter changes with IC-Ach and CPT are moderately-well correlated suggesting that CPT testing may be of some use, particularly among patients with normal endothelial function, however, not an alternative to IC-Ach for diagnosis of coronary

CHANGES IN LIPOPROTEIN INDICATOR AND INDICATOR OF ENDOTHELIAL FUNCTION AFTER IMPLEMENTED CARDIOVASCULAR REHABILITATION PROGRAM

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Jasmina Ranković

2012-09-01

Full Text Available Insufficient physical activity in the world annually is the cause of death of 1.9 million people. According to the data from the World Health Report, physical inactivity is about to become the global problem. Regular physical activity and good physical shape raise the functional capacity and the quality of patient’s life. With physical activity it is possible to improve metabolic, endothelial, lateral-muscular, pulmonary and cardiovascular functions of an organism, but also the function of the autonomous nervous system. The endothelium has the important role in maintaining the normal cardiovascular tonus and blood fluidity by reducing the platelet activity and the adhesion of leukocytes, and also by restricting the reaction of vascular inflammation. The aim of this paper was to present the recent data about effects of cardiovascular rehabilitation and physical training on lipoproteins’ status and markers of endothelial function. The impact of physical activity on the lipid status is accomplished by affecting the enzymes of lipoprotein metabolism, including the lipoprotein and the liver lipase and the movable protein of cholesterol ester (11. The studies point out that aerobic physical activity result in increasing of HDL concentration and the decrease of the triglycerides value, total and LDL cholesterol. The connection, which is dose-dependant, exists between physical activity and the lipid level, as the arguments which suggest that the duration of physical activity is the key parameter in modification of the lipid metabolism. Physical activity leads to the beneficial changes in the cardiovascular and lipid indicators and improves the endothelial function in the secondary prevention of coronary disease. Reduction of the lipid parameters by introducing physical rehabilitation and dietetic regime lie in the basis of secondary prevention of coronary disease. Furthermore, there is a constant improvement in NO biodisposability and therewith the

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

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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...

Arterial Injury and Endothelial Repair: Rapid Recovery of Function after Mechanical Injury in Healthy Volunteers

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Lindsey Tilling

2014-01-01

Full Text Available Objective. Previous studies suggest a protracted course of recovery after mechanical endothelial injury; confounders may include degree of injury and concomitant endothelial dysfunction. We sought to define the time course of endothelial function recovery using flow-mediated dilation (FMD, after ischaemia-reperfusion (IR and mechanical injury in patients and healthy volunteers. The contribution of circulating CD133+/CD34+/VEGFR2+ “endothelial progenitor” (EPC or repair cells to endothelial repair was also examined. Methods. 28 healthy volunteers aged 18–35 years underwent transient forearm ischaemia induced by cuff inflation around the proximal biceps and radial artery mechanical injury induced by inserting a wire through a cannula. A more severe mechanical injury was induced using an arterial sheath and catheter inserted into the radial artery of 18 patients undergoing angiography. Results. IR and mechanical injury produced immediate impairment of FMD (from 6.5 ± 1.2% to 2.9 ± 2.2% and from 7.4 ± 2.3% to 1.5 ± 1.6% for IR and injury, resp., each P<0.001 but recovered within 6 hours and 2 days, respectively. FMD took up to 4 months to recover in patients. Circulating EPC did not change significantly during the injury/recovery period in all subjects. Conclusions. Recovery of endothelial function after IR and mechanical injury is rapid and not associated with a change in circulating EPC.

The research on endothelial function in women and men at risk for cardiovascular disease (REWARD study: methodology

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Lavoie Kim L

2011-08-01

Full Text Available Abstract Background Endothelial function has been shown to be a highly sensitive marker for the overall cardiovascular risk of an individual. Furthermore, there is evidence of important sex differences in endothelial function that may underlie the differential presentation of cardiovascular disease (CVD in women relative to men. As such, measuring endothelial function may have sex-specific prognostic value for the prediction of CVD events, thus improving risk stratification for the overall prediction of CVD in both men and women. The primary objective of this study is to assess the clinical utility of the forearm hyperaemic reactivity (FHR test (a proxy measure of endothelial function for the prediction of CVD events in men vs. women using a novel, noninvasive nuclear medicine -based approach. It is hypothesised that: 1 endothelial dysfunction will be a significant predictor of 5-year CVD events independent of baseline stress test results, clinical, demographic, and psychological variables in both men and women; and 2 endothelial dysfunction will be a better predictor of 5-year CVD events in women compared to men. Methods/Design A total of 1972 patients (812 men and 1160 women undergoing a dipyridamole stress testing were recruited. Medical history, CVD risk factors, health behaviours, psychological status, and gender identity were assessed via structured interview or self-report questionnaires at baseline. In addition, FHR was assessed, as well as levels of sex hormones via blood draw. Patients will be followed for 5 years to assess major CVD events (cardiac mortality, non-fatal MI, revascularization procedures, and cerebrovascular events. Discussion This is the first study to determine the extent and nature of any sex differences in the ability of endothelial function to predict CVD events. We believe the results of this study will provide data that will better inform the choice of diagnostic tests in men and women and bring the quality of

Effects of gastric bypass surgery followed by supervised physical training on inflammation and endothelial function

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Stolberg, Charlotte Røn; Mundbjerg, Lene Hymøller; Funch-Jensen, Peter

2018-01-01

Background and aims: Obesity and physical inactivity are both associated with low-grade inflammation and endothelial dysfunction. Bariatric surgery improves markers of inflammation and endothelial function, but it is unknown if physical training after bariatric surgery can improve these markers...... even further. Therefore, we aimed to investigate the effects of Roux-en-Y gastric bypass (RYGB) followed by physical training on markers of low-grade inflammation and endothelial function. Methods: Sixty patients approved for RYGB underwent examinations pre-surgery, 6, 12, and 24 months post......-surgery. Six months post-surgery, they were randomized 1:1 to an intervention group or a control group. The interventions consisted of two weekly sessions of supervised moderate intensity physical training for a period of 26 weeks. Fasting blood samples were analyzed for concentrations of interleukin 6 (IL-6...

Endothelial-specific inhibition of NF-κB enhances functional haematopoiesis.

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Poulos, Michael G; Ramalingam, Pradeep; Gutkin, Michael C; Kleppe, Maria; Ginsberg, Michael; Crowley, Michael J P; Elemento, Olivier; Levine, Ross L; Rafii, Shahin; Kitajewski, Jan; Greenblatt, Matthew B; Shim, Jae-Hyuck; Butler, Jason M

2016-12-21

Haematopoietic stem cells (HSCs) reside in distinct niches within the bone marrow (BM) microenvironment, comprised of endothelial cells (ECs) and tightly associated perivascular constituents that regulate haematopoiesis through the expression of paracrine factors. Here we report that the canonical NF-κB pathway in the BM vascular niche is a critical signalling axis that regulates HSC function at steady state and following myelosuppressive insult, in which inhibition of EC NF-κB promotes improved HSC function and pan-haematopoietic recovery. Mice expressing an endothelial-specific dominant negative IκBα cassette under the Tie2 promoter display a marked increase in HSC activity and self-renewal, while promoting the accelerated recovery of haematopoiesis following myelosuppression, in part through protection of the BM microenvironment following radiation and chemotherapeutic-induced insult. Moreover, transplantation of NF-κB-inhibited BM ECs enhanced haematopoietic recovery and protected mice from pancytopenia-induced death. These findings pave the way for development of niche-specific cellular approaches for the treatment of haematological disorders requiring myelosuppressive regimens.

Endothelial-specific inhibition of NF-κB enhances functional haematopoiesis

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Poulos, Michael G.; Ramalingam, Pradeep; Gutkin, Michael C.; Kleppe, Maria; Ginsberg, Michael; Crowley, Michael J. P.; Elemento, Olivier; Levine, Ross L.; Rafii, Shahin; Kitajewski, Jan; Greenblatt, Matthew B.; Shim, Jae-Hyuck; Butler, Jason M.

2016-01-01

Haematopoietic stem cells (HSCs) reside in distinct niches within the bone marrow (BM) microenvironment, comprised of endothelial cells (ECs) and tightly associated perivascular constituents that regulate haematopoiesis through the expression of paracrine factors. Here we report that the canonical NF-κB pathway in the BM vascular niche is a critical signalling axis that regulates HSC function at steady state and following myelosuppressive insult, in which inhibition of EC NF-κB promotes improved HSC function and pan-haematopoietic recovery. Mice expressing an endothelial-specific dominant negative IκBα cassette under the Tie2 promoter display a marked increase in HSC activity and self-renewal, while promoting the accelerated recovery of haematopoiesis following myelosuppression, in part through protection of the BM microenvironment following radiation and chemotherapeutic-induced insult. Moreover, transplantation of NF-κB-inhibited BM ECs enhanced haematopoietic recovery and protected mice from pancytopenia-induced death. These findings pave the way for development of niche-specific cellular approaches for the treatment of haematological disorders requiring myelosuppressive regimens. PMID:28000664

Ticagrelor Improves Endothelial Function by Decreasing Circulating Epidermal Growth Factor (EGF

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Francesco Vieceli Dalla Sega

2018-04-01

Full Text Available Ticagrelor is one of the most powerful P2Y12 inhibitor. We have recently reported that, in patients with concomitant Stable Coronary Artery Disease (SCAD and Chronic Obstructive Pulmonary Disease (COPD undergoing percutaneous coronary intervention (PCI, treatment with ticagrelor, as compared to clopidogrel, is associated with an improvement of the endothelial function (Clinical Trial NCT02519608. In the present study, we showed that, in the same population, after 1 month treatment with ticagrelor, but not with clopidogrel, there is a decrease of the circulating levels of epidermal growth factor (EGF and that these changes in circulating levels of EGF correlate with on-treatment platelet reactivity. Furthermore, in human umbilical vein endothelial cells (HUVEC incubated with sera of the patients treated with ticagrelor, but not with clopidogrel there is an increase of p-eNOS levels. Finally, analyzing the changes in EGF and p-eNOS levels after treatment, we observed an inverse correlation between p-eNOS and EGF changes only in the ticagrelor group. Causality between EGF and eNOS activation was assessed in vitro in HUVEC where we showed that EGF decreases eNOS activity in a dose dependent manner. Taken together our data indicate that ticagrelor improves endothelial function by lowering circulating EGF that results in the activation of eNOS in the vascular endothelium.

The Relationship between Proliferative Scars and Endothelial Function in Surgically Revascularized Patients

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Murat Ziyrek

2015-12-01

Full Text Available Background: Proliferative scars are benign fibrotic proliferations which demonstrate abnormal wound healing in response to skin injuries. As postulated in the “response to injury hypothesis”, atherosclerosis is also triggered by an endothelial injury. Keloid and atherosclerotic processes have many pathophysiological and cytological features in common. Aims: In this study, we investigated the relationship between proliferative scars and endothelial function in surgically revascularized patients. We aimed to test the hypothesis that atherosclerosis is a wound healing abnormality. Study Design: Cross-sectional study. Methods: Consecutive patients who were admitted to the cardiology outpatient clinic with a history of coronary artery bypass grafting operation were evaluated. Thirty-three patients with proliferative scars at the median sternotomy site formed the keloid group, and 36 age- and sex-matched patients with no proliferative scar at the median sternotomy site formed the control group. Endothelial function was evaluated by flow-mediated vasodilatation of the brachial artery via ultrasonograhic examination. Results: There is no signicant difference according to the demographic data, biochemical parameters, clinical parameters and number of grafts between keloid and control groups. Endothelial-dependent vasodilatory response was lower in the keloid group than the control group (9.30±3.5 and 18.68±8.2, respectively; p=0.001. Conclusion: This study showed that endothalial dysfunction, which is strongly correlated with atherosclerosis, was more prominent in patients with proliferative scars. As proliferative scars and atherosclerosis have many features in common, we might conclude that atherosclerosis is a wound healing abnormality.

Telmisartan enhances mitochondrial activity and alters cellular functions in human coronary artery endothelial cells via AMP-activated protein kinase pathway.

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Kurokawa, Hirofumi; Sugiyama, Seigo; Nozaki, Toshimitsu; Sugamura, Koichi; Toyama, Kensuke; Matsubara, Junichi; Fujisue, Koichiro; Ohba, Keisuke; Maeda, Hirofumi; Konishi, Masaaki; Akiyama, Eiichi; Sumida, Hitoshi; Izumiya, Yasuhiro; Yasuda, Osamu; Kim-Mitsuyama, Shokei; Ogawa, Hisao

2015-04-01

Mitochondrial dysfunction plays an important role in cellular senescence and impaired function of vascular endothelium, resulted in cardiovascular diseases. Telmisartan is a unique angiotensin II type I receptor blocker that has been shown to prevent cardiovascular events in high risk patients. AMP-activated protein kinase (AMPK) plays a critical role in mitochondrial biogenesis and endothelial function. This study assessed whether telmisartan enhances mitochondrial function and alters cellular functions via AMPK in human coronary artery endothelial cells (HCAECs). In cultured HCAECs, telmisartan significantly enhanced mitochondrial activity assessed by mitochondrial reductase activity and intracellular ATP production and increased the expression of mitochondria related genes. Telmisartan prevented cellular senescence and exhibited the anti-apoptotic and pro-angiogenic properties. The expression of genes related anti-oxidant and pro-angiogenic properties were increased by telmisartan. Telmisartan increased endothelial NO synthase and AMPK phosphorylation. Peroxisome proliferator-activated receptor gamma signaling was not involved in telmisartan-induced improvement of mitochondrial function. All of these effects were abolished by inhibition of AMPK. Telmisartan enhanced mitochondrial activity and exhibited anti-senescence effects and improving endothelial function through AMPK in HCAECs. Telmisartan could provide beneficial effects on vascular diseases via enhancement of mitochondrial activity and modulating endothelial function through AMPK activation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Coniferyl aldehyde attenuates radiation enteropathy by inhibiting cell death and promoting endothelial cell function.

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Jeong, Ye-Ji; Jung, Myung Gu; Son, Yeonghoon; Jang, Jun-Ho; Lee, Yoon-Jin; Kim, Sung-Ho; Ko, Young-Gyo; Lee, Yun-Sil; Lee, Hae-June

2015-01-01

Radiation enteropathy is a common complication in cancer patients. The aim of this study was to investigate whether radiation-induced intestinal injury could be alleviated by coniferyl aldehyde (CA), an HSF1-inducing agent that increases cellular HSP70 expression. We systemically administered CA to mice with radiation enteropathy following abdominal irradiation (IR) to demonstrate the protective effects of CA against radiation-induced gastrointestinal injury. CA clearly alleviated acute radiation-induced intestinal damage, as reflected by the histopathological data and it also attenuated sub-acute enteritis. CA prevented intestinal crypt cell death and protected the microvasculature in the lamina propria during the acute and sub-acute phases of damage. CA induced HSF1 and HSP70 expression in both intestinal epithelial cells and endothelial cells in vitro. Additionally, CA protected against not only the apoptotic cell death of both endothelial and epithelial cells but also the loss of endothelial cell function following IR, indicating that CA has beneficial effects on the intestine. Our results provide novel insight into the effects of CA and suggest its role as a therapeutic candidate for radiation-induced enteropathy due to its ability to promote rapid re-proliferation of the intestinal epithelium by the synergic effects of the inhibition of cell death and the promotion of endothelial cell function.

Cyclic adenosine monophosphate levels and the function of skin microvascular endothelial cells.

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Tuder, R M; Karasek, M A; Bensch, K G

1990-02-01

The maintenance of the normal epithelioid morphology of human dermal microvascular endothelial cells (MEC) grown in vitro depends strongly on the presence of factors that increase intracellular levels of cyclic AMP. Complete removal of dibutyryl cAMP and isobutylmethylxanthine (IMX) from the growth medium results in a progressive transition from an epithelioid to a spindle-shaped cell line. This transition cannot be reversed by the readdition of dibutyryl cAMP and IMX to the growth medium or by addition of agonists that increase cAMP levels. Spindle-shaped MEC lose the ability to express Factor VIII rAG and DR antigens and to bind peripheral blood mononuclear leukocyte (PBML). Ultrastructural analyses of transitional cells and spindle-shaped cells show decreased numbers of Weibel-Palade bodies in transitional cells and their complete absence in spindle-shaped cells. Interferon-gamma alters several functional properties of both epithelioid and spindle-shaped cells. In the absence of dibutyryl cAMP it accelerates the transition from epithelial to spindle-shaped cells, whereas in the presence of cyclic AMP interferon-gamma increases the binding of PBMLs to both epithelioid and spindle-shaped MEC and the endocytic activity of the endothelial cells. These results suggest that cyclic AMP is an important second messenger in the maintenance of several key functions of microvascular endothelial cells. Factors that influence the levels of this messenger in vivo can be expected to influence the angiogenic and immunologic functions of the microvasculature.

Angiocrine functions of organ-specific endothelial cells

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Rafii, Shahin; Butler, Jason M; Ding, Bi-Sen

2016-01-01

Preface Endothelial cells lining blood vessel capillaries are not just passive conduits for delivering blood. Tissue-specific endothelium establish specialized vascular niches that deploy specific sets of growth factors, known as angiocrine factors, which actively participate in inducing, specifying, patterning, and guiding organ regeneration and maintaining homeostasis and metabolism. Angiocrine factors upregulated in response to injury orchestrates self-renewal and differentiation of tissue-specific repopulating resident stem and progenitor cells into functional organs. Uncovering the precise mechanisms whereby physiological-levels of angiocrine factors are spatially and temporally produced, and distributed by organotypic endothelium to repopulating cells, will lay the foundation for driving organ repair without scarring. PMID:26791722

Transplantation of endothelial progenitor cells ameliorates vascular dysfunction and portal hypertension in carbon tetrachloride-induced rat liver cirrhotic model.

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Sakamoto, Masaharu; Nakamura, Toru; Torimura, Takuji; Iwamoto, Hideki; Masuda, Hiroshi; Koga, Hironori; Abe, Mitsuhiko; Hashimoto, Osamu; Ueno, Takato; Sata, Michio

2013-01-01

In cirrhosis, sinusoidal endothelial cell injury results in increased endothelin-1 (ET-1) and decreased nitric oxide synthase (NOS) activity, leading to portal hypertension. However, the effects of transplanted endothelial progenitor cells (EPCs) on the cirrhotic liver have not yet been clarified. We investigated whether EPC transplantation reduces portal hypertension. Cirrhotic rats were created by the administration of carbon tetrachloride (CCl(4) ) twice weekly for 10 weeks. From week 7, rat bone marrow-derived EPCs were injected via the tail vein in this model once a week for 4 weeks. Endothelial NOS (eNOS), vascular endothelial growth factor (VEGF) and caveolin expressions were examined by Western blots. Hepatic tissue ET-1 was measured by a radioimmunoassay (RIA). Portal venous pressure, mean aortic pressure, and hepatic blood flow were measured. Endothelial progenitor cell transplantation reduced liver fibrosis, α-smooth muscle actin-positive cells, caveolin expression, ET-1 concentration and portal venous pressure. EPC transplantation increased hepatic blood flow, protein levels of eNOS and VEGF. Immunohistochemical analyses of eNOS and isolectin B4 demonstrated that the livers of EPC-transplanted animals had markedly increased vascular density, suggesting reconstitution of sinusoidal blood vessels with endothelium. Transplantation of EPCs ameliorates vascular dysfunction and portal hypertension, suggesting this treatment may provide a new approach in the therapy of portal hypertension with liver cirrhosis. © 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Clinicoroentgenological diagnosis of chronic venous ovarian insufficiency

International Nuclear Information System (INIS)

Grakova, L.S.; Galkin, E.V.; Naumova, E.B.

1989-01-01

The paper is devoted to clinicoroentgenological correlations of venous renogonadal hemodynamics in 168 women of reproductive age (151 women with infertility, habitual abortion, disordered menstrual function and 17 patients without disorders of the reproductive tract). Clinicolaboratory investigation was followed by visceral and parietal flebography for the detection of a pathological venous reflux into the ovarian pampiniform plexus. Clinicoroentgenological semiotics of chronic venous ovarian insufficiency was analyzed. Infertility was shown to be the main clinical manifestation of ovarian varicocele

The effect of chronic heart failure and type 2 diabetes on insulin-stimulated endothelial function is similar and additive

DEFF Research Database (Denmark)

Falskov, Britt; Hermann, Thomas Steffen; Rask-Madsen, Christian

2011-01-01

AIM: Chronic heart failure is associated with endothelial dysfunction and insulin resistance. The aim of this investigation was to study insulin-stimulated endothelial function and glucose uptake in skeletal muscles in patients with heart failure in comparison to patients with type 2 diabetes. ME...... in similar vascular insulin resistance and reduced muscular insulin-stimulated glucose uptake. The effects of systolic heart failure and type 2 diabetes appear to be additive.......AIM: Chronic heart failure is associated with endothelial dysfunction and insulin resistance. The aim of this investigation was to study insulin-stimulated endothelial function and glucose uptake in skeletal muscles in patients with heart failure in comparison to patients with type 2 diabetes...

Validation of Na,K-ATPase pump function of corneal endothelial cells for corneal regenerative medicine.

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Hatou, Shin; Higa, Kazunari; Inagaki, Emi; Yoshida, Satoru; Kimura, Erika; Hayashi, Ryuhei; Tsujikawa, Motokazu; Tsubota, Kazuo; Nishida, Kohji; Shimmura, Shigeto

2013-12-01

Tissue-engineering approaches to cultivate corneal endothelial cells (CECs) or induce CECs from stem cells are under investigation for the treatment of endothelial dysfunction. Before clinical application, a validation method to determine the quality of these cells is required. In this study, we quantified the endothelial pump function required for maintaining the corneal thickness using rabbit CECs (RCECs) and a human CEC line (B4G12). The potential difference of RCECs cultured on a permeable polyester membrane (Snapwell), B4G12 cells on Snapwell, or B4G12 cells on a collagen membrane (CM6) was measured by an Ussing chamber system, and the effect of different concentrations of ouabain (Na,K-ATPase specific inhibitor) was obtained. A mathematical equation derived from the concentration curve revealed that 2 mM ouabain decreases pump function of RCECs to 1.0 mV, and 0.6 mM ouabain decreases pump function of B4G12 on CM6 to 1.0 mV. Ouabain injection into the anterior chamber of rabbit eyes at a concentration of pump function >1.0 mV is required to maintain the corneal thickness. These results can be used for standardization of CEC pump function and validation of tissue-engineered CEC sheets for clinical use.

Blueberries improve endothelial function, but not blood pressure, in adults with metabolic syndrome: a randomized, double-blind, placebo-controlled clinical trial.

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Stull, April J; Cash, Katherine C; Champagne, Catherine M; Gupta, Alok K; Boston, Raymond; Beyl, Robbie A; Johnson, William D; Cefalu, William T

2015-05-27

Blueberry consumption has been shown to have various health benefits in humans. However, little is known about the effect of blueberry consumption on blood pressure, endothelial function and insulin sensitivity in humans. The present study investigated the role of blueberry consumption on modifying blood pressure in subjects with metabolic syndrome. In addition, endothelial function and insulin sensitivity (secondary measurements) were also assessed. A double-blind and placebo-controlled study was conducted in 44 adults (blueberry, n = 23; and placebo, n = 21). They were randomized to receive a blueberry or placebo smoothie twice daily for six weeks. Twenty-four-hour ambulatory blood pressure, endothelial function and insulin sensitivity were assessed pre- and post-intervention. The blood pressure and insulin sensitivity did not differ between the blueberry and placebo groups. However, the mean change in resting endothelial function, expressed as reactive hyperemia index (RHI), was improved significantly more in the group consuming the blueberries versus the placebo group (p = 0.024). Even after adjusting for confounding factors, i.e., the percent body fat and gender, the blueberry group still had a greater improvement in endothelial function when compared to their counterpart (RHI; 0.32 ± 0.13 versus -0.33 ± 0.14; p = 0.0023). In conclusion, daily dietary consumption of blueberries did not improve blood pressure, but improved (i.e., increased) endothelial function over six weeks in subjects with metabolic syndrome.

Catalase activity prevents exercise-induced up-regulation of vasoprotective proteins in venous tissue

OpenAIRE

Dao, Vu Thao-Vi; Floeren, Melanie; Kumpf, Stephanie; Both, Charlotte; Peter, B?rbel; Balz, Vera; Suvorava, Tatsiana; Kojda, Georg

2011-01-01

Abstract Physical activity induces favourable changes of arterial gene expression and protein activity, although little is known about its effect in venous tissue. Although our understanding of the initiating molecular signals is still incomplete, increased expression of endothelial nitric oxide synthase (eNOS) is considered a key event. This study sought to investigate the effects of two different training protocols on the expression of eNOS and extracellular superoxide dismutase (ecSOD) in ...

Anatomic and functional outcomes of pharmacomechanical and catheter-directed thrombolysis of iliofemoral deep venous thrombosis.

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Hager, Eric; Yuo, Theodore; Avgerinos, Efthymios; Naddaf, Abdullah; Jeyabalan, Geetha; Marone, Luke; Chaer, Rabih

2014-07-01

Pharmacomechanical thrombolysis (PMT) and catheter-directed thrombolysis (CDT) are commonly used for the treatment of iliofemoral deep venous thrombosis (DVT). The purpose of this study was to examine the short- and long-term venous patency and venous valvular function as well as clinical outcomes of patients treated for iliofemoral DVT by PMT and CDT. A retrospective review of all patients with symptomatic DVT treated between 2006 and 2011 with PMT or CDT was performed. All patients were treated by local tissue plasminogen activator delivered with PMT or CDT. Patients were divided into two groups on the basis of initial treatment modality: patients treated by PMT alone (group 1), and those who underwent PMT and CDT or CDT alone (group 2). Group comorbidities, initial presenting symptoms, and Clinical, Etiologic, Anatomic, and Pathologic (CEAP) classification scores were compared. Postprocedural duplex ultrasound was used to assess valve function and treated vein patency rates. At all visits, Villalta and CEAP scores were recorded and compared. Group demographic and procedural results were analyzed by Fisher exact test for dichotomous variables and Kruskal-Wallis equality-of-populations rank test for the ordinal and continuous data. Kaplan-Meier survival estimates were used to assess preserved valve function as well as primary and secondary patency rates. There were 79 patients with 102 limbs treated for extensive iliofemoral DVT (median age, 51.5 years; range, 16.6-83.8 years). There were 18 patients in group 1 and 61 patients in group 2 (PMT + CDT [n = 54] or CDT alone [n = 7]). There were no differences in demographics or comorbidities between groups aside from malignant disease, which was more common in group 1 (35.3% vs 11.5%; P = .03). A total of 102 limbs were analyzed, 24 in group 1 and 78 in group 2. Patients in group 1 had a shorter symptom duration compared with group 2 (7 days vs 16 days; P = .011). The median number of procedures in group 1

Effects of Oral Glucose Load on Endothelial Function and on Insulin and Glucose Fluctuations in Healthy Individuals

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A. Major-Pedersen

2008-01-01

Full Text Available Background/aims. Postprandial hyperglycemia, an independent risk factor for cardiovascular disease, is accompanied by endothelial dysfunction. We studied the effect of oral glucose load on insulin and glucose fluctuations, and on postprandial endothelial function in healthy individuals in order to better understand and cope with the postprandial state in insulin resistant individuals. Methods. We assessed post-oral glucose load endothelial function (flow mediated dilation, plasma insulin, and blood glucose in 9 healthy subjects. Results. The largest increases in delta FMD values (fasting FMD value subtracted from postprandial FMD value occurred at 3 hours after both glucose or placebo load, respectively: 4.80±1.41 (P = .009 and 2.34±1.47 (P = .15. Glucose and insulin concentrations achieved maximum peaks at one hour post-glucose load. Conclusion. Oral glucose load does not induce endothelial dysfunction in healthy individuals with mean insulin and glucose values of 5.6 mmol/L and 27.2 mmol/L, respectively, 2 hours after glucose load.

Long-term, regular remote ischemic preconditioning improves endothelial function in patients with coronary heart disease

Energy Technology Data Exchange (ETDEWEB)

Liang, Y.; Li, Y.P.; He, F.; Liu, X.Q.; Zhang, J.Y. [Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China)

2015-04-28

Remote ischemic preconditioning (RIPre) can prevent myocardial injury. The purpose of this study was to assess the beneficial effects of long-term regular RIPre on human arteries. Forty patients scheduled for coronary artery bypass graft (CABG) surgery were assigned randomly to a RIPre group (n=20) or coronary heart disease (CHD) group (n=20). Twenty patients scheduled for mastectomy were enrolled as a control group. RIPre was achieved by occluding arterial blood flow 5 min with a mercury sphygmomanometer followed by a 5-min reperfusion period, and this was repeated 4 times. The RIPre procedure was repeated 3 times a day for 20 days. In all patients, arterial fragments discarded during surgery were collected to evaluate endothelial function by flow-mediated dilation (FMD), CD34{sup +} monocyte count, and endothelial nitric oxide synthase (eNOS expression). Phosphorylation levels of STAT-3 and Akt were also assayed to explore the underlying mechanisms. Compared with the CHD group, long-term regular RIPre significantly improved FMD after 20 days (8.5±2.4 vs 4.9±4.2%, P<0.05) and significantly reduced troponin after CABG surgery (0.72±0.31 and 1.64±0.19, P<0.05). RIPre activated STAT-3 and increased CD34{sup +} endothelial progenitor cell counts found in arteries. Long-term, regular RIPre improved endothelial function in patients with CHD, possibly due to STAT-3 activation, and this may have led to an increase in endothelial progenitor cells.

Acetylcysteine reduces plasma homocysteine concentration and improves pulse pressure and endothelial function in patients with end-stage renal failure

DEFF Research Database (Denmark)

Scholze, Alexandra; Rinder, Christiane; Beige, Joachim

2004-01-01

Increased oxidative stress, elevated plasma homocysteine concentration, increased pulse pressure, and impaired endothelial function constitute risk factors for increased mortality in patients with end-stage renal failure.......Increased oxidative stress, elevated plasma homocysteine concentration, increased pulse pressure, and impaired endothelial function constitute risk factors for increased mortality in patients with end-stage renal failure....

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

Role of insulin in regulation of Na+-/K+-dependent ATPase activity and pump function in corneal endothelial cells.

Science.gov (United States)

Hatou, Shin; Yamada, Masakazu; Akune, Yoko; Mochizuki, Hiroshi; Shiraishi, Atsushi; Joko, Takeshi; Nishida, Teruo; Tsubota, Kazuo

2010-08-01

The Na(+)-/K(+)-dependent ATPase (Na,K-ATPase) expressed in the basolateral membrane of corneal endothelial cells plays an important role in the pump function of the corneal endothelium. The role of insulin in the regulation of Na,K-ATPase activity and pump function in corneal endothelial cells was investigated. Confluent monolayers of mouse corneal endothelial cells were exposed to insulin. ATPase activity was evaluated by spectrophotometric measurement of phosphate released from ATP with the use of ammonium molybdate; Na,K-ATPase activity was defined as the portion of total ATPase activity sensitive to ouabain. Pump function was measured with the use of a Ussing chamber; pump function attributable to Na,K-ATPase activity was defined as the portion of the total short-circuit current sensitive to ouabain. Western blot analysis and immunocytochemistry were performed to measure the expression of the Na,K-ATPase alpha(1)-subunit. Insulin increased the Na,K-ATPase activity and pump function of cultured corneal endothelial cells. These effects were blocked by protein kinase C (PKC) inhibitors and protein phosphatases 1 and 2A inhibitor. Western blot analysis indicated that insulin decreased the ratio of the inactive Na,K-ATPase alpha(1)-subunit. Immunocytochemistry indicated that insulin increased the cell surface expression of the Na,K-ATPase alpha(1)-subunit. These results suggest that insulin increases the Na,K-ATPase activity and pump function of cultured corneal endothelial cells. The effect of insulin is mediated by PKC and presumably results in the activation of PP1, 2A, or both, which are essential for activating Na,K-ATPase by alpha(1)-subunit dephosphorylation.

Is endothelial microvascular function equally impaired among patients with chronic Chagas and ischemic cardiomyopathy?

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Borges, Juliana Pereira; Mendes, Fernanda de Souza Nogueira Sardinha; Lopes, Gabriella de Oliveira; Sousa, Andréa Silvestre de; Mediano, Mauro Felippe Felix; Tibiriçá, Eduardo

2018-08-15

Chronic Chagas cardiomyopathy (CCC) and cardiomyopathies due to other etiologies involve differences in pathophysiological pathways that are still unclear. Systemic microvascular abnormalities are associated with the pathogenesis of ischemic heart disease. However, systemic microvascular endothelial function in CCC remains to be elucidated. Thus, we compared the microvascular endothelial function of patients presenting with CCC to those with ischemic cardiomyopathy disease. Microvascular reactivity was assessed in 21 patients with cardiomyopathy secondary to Chagas disease, 21 patients with cardiomyopathy secondary to ischemic disease and 21 healthy controls. Microvascular blood flow was assessed in the skin of the forearm using laser speckle contrast imaging coupled with iontophoresis of acetylcholine (ACh). Peak increase in forearm blood flow with ACh iontophoresis in relation to baseline was greater in healthy controls than in patients with heart disease (controls: 162.7 ± 58.4% vs. ischemic heart disease: 74.1 ± 48.3% and Chagas: 85.1 ± 68.1%; p < 0.0001). Patients with Chagas and ischemic cardiomyopathy presented similar ACh-induced changes from baseline in skin blood flow (p = 0.55). Endothelial microvascular function was equally impaired among patients with CCC and ischemic cardiomyopathy. Copyright © 2018 Elsevier B.V. All rights reserved.

Protective effect of anti-oxidants on endothelial function in young Korean-Asians compared to Caucasians

Science.gov (United States)

Yim, Jongeun; Petrofsky, Jerrold; Berk, Lee; Daher, Noha; Lohman, Everett; Moss, Abigail; Cavalcanti, Paula

2012-01-01

Summary Background Previous studies show that Asians have an impaired blood flow response (BFR) to occlusion after a single high fat (HF) meal. The mechanism is believed to be the presence and susceptibility to high free radicals in their blood. The free radical concentration after a HF meal has not been examined in Asians. Further the BFR to heat after a single HF meal in Koreans has not been measured. Material/Methods This study evaluated postprandial endothelial function by measuring the BFR to vascular occlusion and local heat before and after a HF meal and the interventional effects of anti-oxidant vitamins on improving endothelial function in young Korean-Asians (K) compared to Caucasians (C) with these assessments. Ten C and ten K participated in the study (mean age 25.3±3.6 years old). BFR to vascular occlusion and local heat and oxidative stress were assessed after a single low fat (LF) and HF meal at 2 hours compared to baseline. After administration of vitamins (1000 mg of vitamin C, 800 IU of vitamin E, and 300 mg of Coenzyme Q-10) for 14 days, the same measurements were made. Results This study showed that the skin BFR to vascular occlusion and local heat following a HF meal significantly decreased and free radicals significantly increased at 2 hours compared to baseline in K (pvitamins were given, the BFR to vascular occlusion and local heat before and after HF meal were not significantly different in K and C. Conclusions These findings suggest that even a single HF meal can reduce endothelial response to stress through an oxidative stress mechanism but can be blocked by antioxidants, probably through scavenging free radicals in K. Since endothelial function improved even before a HF meal in K, endothelial damage from an Americanized diet may be reduced in K by antioxidants. PMID:22847195

Asymmetric Dimethylarginine Plasma Levels and Endothelial Function in Newly Diagnosed Type 2 Diabetic Patients

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Francesco Perticone

2012-10-01

Full Text Available It is now well established that major risk factors for cardiovascular diseases (CVD impact upon endothelial function by decreasing nitric oxide (NO bioavailability. Asymmetric dimethylarginine (ADMA, an endogenous analog of l-arginine, is able to inhibit the activity of endothelial-NO synthase, promoting endothelial dysfunction. Type 2 diabetes (T2D is characterized by a reduced endothelium-dependent vasodilation and increased ADMA levels and ADMA is strongly associated with micro- and macrovascular diabetic complications. However, there are not a lot of data about the role of ADMA on endothelial function in newly diagnosed T2D patients without cardiovascular (CV complications. For this aim, we have enrolled forty-five newly diagnosed T2D patients, evaluated by a oral glucose tolerance test, and thirty normal subjects. Endothelium-dependent and -independent vasodilatation was investigated by intra-arterial infusion of increasing doses of acetylcholine (ACh and sodium nitroprusside. ADMA was measured by high-performance liquid chromatography and insulin resistance (IR by HOMA. Newly diagnosed T2D patients showed higher ADMA and l-arginine mean values in comparison with normal subjects and a significantly reduced ACh-stimulated forearm blood flow (FBF. In T2D patients FBF was significantly and inversely correlated with ADMA (r = −0.524, p < 0.0001 and in a multivariate regression analysis, ADMA resulted the stronger predictor of FBF, explaining the 27.5% of variability (p < 0.0001. In conclusion, ADMA was strongly related to endothelial dysfunction also in patients with newly diagnosed T2D, without clinically manifest vascular complications. This field is of great interest for understanding the mechanisms underlying the pathogenesis of diabetic disease and its CV complications.

Neutrophil-endothelial cell interactions on endothelial monolayers grown on micropore filters.

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Taylor, R F; Price, T H; Schwartz, S M; Dale, D C

1981-01-01

We have developed a technique for growing endothelial monolayers on micropore filters. These monolayers demonstrate confluence by phase and electron microscopy and provide a functional barrier to passage of radiolabeled albumin. Neutrophils readily penetrate the monolayer in response to chemotaxin, whereas there is little movement in the absence of chemotaxin. This system offers unique advantages over available chemotaxis assays and may have wider applications in the study of endothelial function. Images PMID:7007441

Endothelial function predicts progression of carotid intima-media thickness

DEFF Research Database (Denmark)

Halcox, J.P.; Donald, A.E.; Ellins, E.

2009-01-01

significant after adjustment for risk factors whether entered as separate variables or as Framingham Risk Score. Further adjustment for waist circumference, triglycerides, and employment grade had no significant effect. CONCLUSIONS: Systemic endothelial function was associated with progression of preclinical...... to its impact on the evolution of the atherosclerotic substrate. Flow-mediated dilatation testing provides an integrated vascular measure that may aid the prediction of structural disease evolution and represents a potential short- to intermediate-term outcome measure for evaluation of preventive...

Vascular endothelial growth factor impairs the functional ability of dendritic cells through Id pathways

International Nuclear Information System (INIS)

Laxmanan, Sreenivas; Robertson, Stuart W.; Wang Enfeng; Lau, Julie S.; Briscoe, David M.; Mukhopadhyay, Debabrata

2005-01-01

Vascular endothelial growth factor (VEGF) is an angiogenic cytokine that plays an important role in tumor growth and progression. Recent evidence suggests an alternate, albeit indirect, role of VEGF on host immune response to tumors. VEGF appears to diminish host immunity by altering the function of major antigen-presenting cells such as dendritic cells (DCs) [D.I. Gabrilovich, T. Ishida, S. Nadaf, J.E. Ohm, D.P. Carbone, Antibodies to vascular endothelial growth factor enhance the efficacy of cancer immunotherapy by improving endogenous dendritic cell function, Clin. Cancer Res. 5 (1999) 2963-2970, D. Gabrilovich, T. Ishida, T. Oyama, S. Ran, V. Kravtsov, S. Nadaf, D.P. Carbone, Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo, Blood 92 (1998) 4150-4166, T. Oyama, S. Ran, T. Ishida, S. Nadaf, L. Kerr, D.P. Carbone, D.I. Gabrilovich, Vascular endothelial growth factor affects dendritic cell maturation through the inhibition of nuclear factor-kappa B activation in hemopoietic progenitor cells, J. Immunol. 160 (1998) 1224-1232.]. DCs are prime initiators of host immunity as they are known to activate both primary as well as secondary immune responses [J. Banchereau, F. Briere, C. Caux, J. Davoust, S. Lebecque, Y.J. Liu, B. Pulendran, K. Palucka, Immunobiology of dendritic cells, Ann. Rev. Immunol. 18 (2000) 767-811.]. However, the exact nature of how VEGF suppresses DC function is not fully clear. In this report, we show that DCs cultured in the presence of VEGF are less potent in stimulating antigen-specific T-cells. Furthermore, by using DCs derived from Id1 -/- mice that are defective in Flt-1 signaling, we demonstrated that the inhibitory function of VEGF on DC function is most likely mediated by Flt-1. Thus, the role of VEGF in downregulating host immunity may highlight a unique role of VEGF in the pathogenesis of cancer

Penile venous surgery for treating erectile dysfunction: Past, present, and future perspectives with regard to new insights in venous anatomy

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Cheng-Hsing Hsieh

2016-06-01

Full Text Available In the physiologic model of normal erectile function, a healthy veno-occlusive mechanism is essential to initiate and maintain a rigid erection. The surgical treatment of patients with venous leakage, which is synonymous with corporoveno-occlusive dysfunction (CVOD, was based on the decreased venous outflow during the erection process. The initial reports of short-term results were promising, but the long-term benefits of penile venous ligation surgery were limited. Most clinical guideline panels concluded that surgeries performed in an attempt to limit the venous outflow of the penis were not recommended. Consequently, this surgery was nearly abandoned in most medical societies worldwide. These unfavorable postoperative outcomes seemed attributable to the indispensable usage of electrocautery and insufficient venous management, based on conventional penile venous anatomy. Advances in better understanding of human penile venous anatomy has enabled the development of refined penile venous stripping surgery. The thorough stripping surgery is an even more radical procedure, which is an even more radical procedure, and seems to be a viable option for the treatment of CVOD, however, there is still a need for further study with well-defined diagnostic criteria, and standardized patient and partner outcome assessment.

Cerebral venous outflow and cerebrospinal fluid dynamics

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Clive B. Beggs

2014-12-01

Full Text Available In this review, the impact of restricted cerebral venous outflow on the biomechanics of the intracranial fluid system is investigated. The cerebral venous drainage system is often viewed simply as a series of collecting vessels channeling blood back to the heart. However there is growing evidence that it plays an important role in regulating the intracranial fluid system. In particular, there appears to be a link between increased cerebrospinal fluid (CSF pulsatility in the Aqueduct of Sylvius and constricted venous outflow. Constricted venous outflow also appears to inhibit absorption of CSF into the superior sagittal sinus. The compliance of the cortical bridging veins appears to be critical to the behaviour of the intracranial fluid system, with abnormalities at this location implicated in normal pressure hydrocephalus. The compliance associated with these vessels appears to be functional in nature and dependent on the free egress of blood out of the cranium via the extracranial venous drainage pathways. Because constricted venous outflow appears to be linked with increased aqueductal CSF pulsatility, it suggests that inhibited venous blood outflow may be altering the compliance of the cortical bridging veins.

Pathophysiology of spontaneous venous gas embolism

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Lambertsen, C. J.; Albertine, K. H.; Pisarello, J. B.; Flores, N. D.

1991-01-01

The use of controllable degrees and durations of continuous isobaric counterdiffusion venous gas embolism to investigate effects of venous gas embolism upon blood, cardiovascular, and respiratory gas exchange function, as well as pathological effects upon the lung and its microcirculation is discussed. Use of N2O/He counterdiffusion permitted performance of the pathophysiologic and pulmonary microstructural effects at one ATA without hyperbaric or hypobaric exposures.

Endothelial function and insulin resistance in polycystic ovary syndrome: the effects of medical therapy.

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Teede, Helena J; Meyer, Caroline; Hutchison, Samantha K; Zoungas, Sophia; McGrath, Barry P; Moran, Lisa J

2010-01-01

To assess the interaction between insulin resistance and endothelial function and the optimal treatment strategy addressing cardiovascular risk in polycystic ovary syndrome. Randomized controlled trial. Controlled clinical study. Overweight age- and body mass index-matched women with polycystic ovary syndrome. Six months metformin (1 g two times per day, n = 36) or oral contraceptive pill (OCP) (35 microg ethinyl E(2)-2 mg cytoproterone acetate, n = 30). Fasting and oral glucose tolerance test glucose and insulin levels, endothelial function (flow-mediated dilation, asymmetric dimethylarginine, plasminogen activator inhibitor-1, von Willebrand factor), inflammatory markers (high-sensitivity C-reactive protein), lipids, and hyperandrogenism. The OCP increased levels of glucose and insulin on oral glucose tolerance test, high-sensitivity C-reactive protein, triglycerides, and sex-hormone binding globulin and decreased levels of low-density lipoprotein cholesterol and T. Metformin decreased levels of fasting insulin, oral glucose tolerance test insulin, high-density lipoprotein cholesterol, and high-sensitivity C-reactive protein. Flow-mediated dilation increased only with metformin (+2.2% +/- 4.8%), whereas asymmetric dimethylarginine decreased equivalently for OCP and metformin (-0.3 +/- 0.1 vs. -0.1 +/- 0.1 mmol/L). Greater decreases in plasminogen activator inhibitor-1 occurred for the OCP than for metformin (-1.8 +/- 1.6 vs. -0.7 +/- 1.7 U/mL). In polycystic ovary syndrome, metformin improves insulin resistance, inflammatory markers, and endothelial function. The OCP worsens insulin resistance and glucose homeostasis, inflammatory markers, and triglycerides and has neutral or positive endothelial effects. The effect of the OCP on cardiovascular risk in polycystic ovary syndrome is unclear. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Preserved microvascular endothelial function in young, obese adults with functional loss of nitric oxide signaling

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John eHarrell

2015-12-01

Full Text Available Data indicate endothelium-dependent dilation (EDD may be preserved in the skeletal muscle microcirculation of young, obese adults. Preserved EDD might be mediated by compensatory mechanisms, impeding insight into preclinical vascular dysfunction. We aimed to determine the functional roles of nitric oxide synthase (NOS and cyclooxygenase (COX toward EDD in younger obese adults. We first hypothesized EDD would be preserved in young, obese adults. Further, we hypothesized a reduced contribution of NOS in young, obese adults would be replaced by increased COX signaling. Microvascular EDD was assessed with Doppler ultrasound and brachial artery infusion of acetylcholine (ACh in younger (27±1 yr obese (n=29 and lean (n=46 humans. Individual and combined contributions of NOS and COX were examined with intra-arterial infusions of L-NMMA and ketorolac, respectively. Vasodilation was quantified as an increase in forearm vascular conductance (ΔFVC. Arterial endothelial cell biopsies were analyzed for protein expression of endothelial nitric oxide synthase (eNOS. ΔFVC to ACh was similar between groups. After L-NMMA, ΔFVC to ACh was greater in obese adults (p<0.05. There were no group differences in ΔFVC to ACh with ketorolac. With combined NOS-COX inhibition, ΔFVC was greater in obese adults at the intermediate dose of ACh. Surprisingly, arterial endothelial cell eNOS and phosphorylated eNOS were similar between groups. Younger obese adults exhibit preserved EDD and eNOS expression despite functional dissociation of NOS-mediated vasodilation and similar COX signaling. Compensatory NOS- and COX-independent vasodilatory mechanisms conceal reduced NOS contributions in otherwise healthy obese adults early in life, which may contribute to vascular dysfunction.

Endothelial microparticles: Pathogenic or passive players in endothelial dysfunction in autoimmune rheumatic diseases?

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McCarthy, E M; Wilkinson, F L; Parker, B; Alexander, M Y

2016-11-01

Autoimmune rheumatic diseases are characterised by systemic inflammation and complex immunopathology, with an increased risk of cardiovascular disease, initiated by endothelial dysfunction in a chronic inflammatory environment. Endothelial microparticles (EMPs) are released into the circulation from activated endothelial cells and may therefore, reflect disease severity, vascular and endothelial dysfunction, that could influence disease pathogenesis via autocrine/paracrine signalling. The exact function of EMPs in rheumatic disease remains unknown, and this has initiated research to elucidate EMP composition and function, which may be determined by the mode of endothelial activation and the micro environment. To date, EMPs are thought to play a role in angiogenesis, thrombosis and inflammation by transferring specific proteins and microRNAs (miRs) to target cells. Here, we review the mechanisms underlying the generation and composition of EMPs and the clinical and experimental studies describing the involvement of EMPs in rheumatic diseases, since we have previously shown endothelial dysfunction and an elevated risk of cardiovascular disease are characteristics in systemic lupus erythematosus. We will also discuss the potential of EMPs as future biomarkers of cardiovascular risk in these diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Elevated plasma factor VIII enhances venous thrombus formation in rabbits: contribution of factor XI, von Willebrand factor and tissue factor.

Science.gov (United States)

Sugita, Chihiro; Yamashita, Atsushi; Matsuura, Yunosuke; Iwakiri, Takashi; Okuyama, Nozomi; Matsuda, Shuntaro; Matsumoto, Tomoko; Inoue, Osamu; Harada, Aya; Kitazawa, Takehisa; Hattori, Kunihiro; Shima, Midori; Asada, Yujiro

2013-07-01

Elevated plasma levels of factor VIII (FVIII) are associated with increased risk of deep venous thrombosis. The aim of this study is to elucidate how elevated FVIII levels affect venous thrombus formation and propagation in vivo. We examined rabbit plasma FVIII activity, plasma thrombin generation, whole blood coagulation, platelet aggregation and venous wall thrombogenicity before and one hour after an intravenous infusion of recombinant human FVIII (rFVIII). Venous thrombus induced by the endothelial denudation of rabbit jugular veins was histologically assessed. Thrombus propagation was evaluated as indocyanine green fluorescence intensity. Argatroban, a thrombin inhibitor, and neutralised antibodies for tissue factor (TF), factor XI (FXI), and von Willebrand factor (VWF) were infused before or after thrombus induction to investigate their effects on venous thrombus formation or propagation. Recombinant FVIII (100 IU/kg) increased rabbit plasma FVIII activity two-fold and significantly enhanced whole blood coagulation and total plasma thrombin generation, but did not affect initial thrombin generation time, platelet aggregation and venous wall thrombogenicity. The rFVIII infusion also increased the size of venous thrombus 1 hour after thrombus induction. Argatroban and the antibodies for TF, FXI or VWF inhibited such enhanced thrombus formation and all except TF suppressed thrombus propagation. In conclusion, elevated plasma FVIII levels enhance venous thrombus formation and propagation. Excess thrombin generation by FXI and VWF-mediated FVIII recruitment appear to contribute to the growth of FVIII-driven venous thrombus.

Effects of oral glucose load on endothelial function and on insulin and glucose fluctuations in healthy individuals

DEFF Research Database (Denmark)

Major-Pedersen, A; Ihlemann, N; Hermann, T S

2008-01-01

to better understand and cope with the postprandial state in insulin resistant individuals. METHODS: We assessed post-oral glucose load endothelial function (flow mediated dilation), plasma insulin, and blood glucose in 9 healthy subjects. RESULTS: The largest increases in delta FMD values (fasting FMD......BACKGROUND/AIMS: Postprandial hyperglycemia, an independent risk factor for cardiovascular disease, is accompanied by endothelial dysfunction. We studied the effect of oral glucose load on insulin and glucose fluctuations, and on postprandial endothelial function in healthy individuals in order...... value subtracted from postprandial FMD value) occurred at 3 hours after both glucose or placebo load, respectively: 4.80 +/- 1.41 (P = .009) and 2.34 +/- 1.47 (P = .15). Glucose and insulin concentrations achieved maximum peaks at one hour post-glucose load. CONCLUSION: Oral glucose load does not induce...

ALK5 inhibition maintains islet endothelial cell survival but does not enhance islet graft revascularisation or function.

Science.gov (United States)

King, A J F; Clarkin, C E; Austin, A L F; Ajram, L; Dhunna, J K; Jamil, M O; Ditta, S I; Ibrahim, S; Raza, Z; Jones, P M

2015-01-01

Islet transplantation is a potential treatment for Type 1 diabetes but long term graft function is suboptimal. The rich supply of intraislet endothelial cells diminishes rapidly after islet isolation and culture, which affects the revascularisation rate of islets after transplantation. The ALK5 pathway inhibits endothelial cell proliferation and thus inhibiting ALK5 is a potential target for improving endothelial cell survival. The aim of the study was to establish whether ALK5 inhibition prevents the loss of intraislet endothelial cells during islet culture and thus improves the functional survival of transplanted islets by enhancing their subsequent revascularisation after implantation. Islets were cultured for 48 h in the absence or presence of 2 different ALK inhibitors: SB-431542 or A-83-01. Their vascular density after culture was analysed using immunohistochemistry. Islets pre-cultured with the ALK5 inhibitors were implanted into streptozotocin-diabetic mice for either 3 or 7 days and blood glucose concentrations were monitored and vascular densities of the grafts were analysed. Islets cultured with ALK5 inhibitors had higher vascular densities than control-cultured islets. Three days after implantation, endothelial cell numbers in islet grafts were minimal, irrespective of treatment during culture. Seven days after implantation, endothelial cells were evident within the islet grafts but there was no difference between control-cultured islets and islets pre-treated with an ALK5 inhibitor. Blood glucose concentrations were no different between the treatment groups. In conclusion, inhibition of ALK5 improved intraislet endothelial cell numbers after islet culture, but this effect was lost in the early post-transplantation period. © Georg Thieme Verlag KG Stuttgart · New York.

[Effect of L-arginine on platelet aggregation, endothelial function adn exercise tolerance in patients with stable angina pectoris].

Science.gov (United States)

Sozykin, A V; Noeva, E A; Balakhonova, T V; Pogorelova, O A; Men'shikov, M Iu

2000-01-01

Examination of the action of donor NO (L-arginine) on platelet aggregation, endothelial function and exercise tolerance in patients with stable angina of effort (SAE). 42 patients with SAE (functional class I-II) and 10 healthy volunteers (control group) were assigned to two groups. 22 patients of group 1 were randomized to cross-over. They received cardiket (60 mg/day for 10 days or cardiket (60 mg/day) in combination with L-arginine (15 g/day for 10 days). 20 SAE patients of group 2 and control group received L-arginine (15 g/day for 10 days). In each group blood lipids were examined, and bicycle exercise test (BET) was performed. In addition, platelet aggregation and endothelial function were studied in group 2 and control group before and after the course of L-arginine. Compared to control group, endothelial function significantly improved in group 2 (from 5.0 +/- 2.9 to 7.8 +/- 4.1% vs 7.1 +/- 1.9 to 6.6 +/- 4.8%) (M +/- SD). BET duration increased in all the patients. After ADP addition in concentrations 1.5, 2.0, and 5.0 micromol/l platelet aggregation declined in 17 patients except 3 in whom the aggregation remained unchanged. Positive effect of L-arginine on endothelial function, exercise tolerance and platelet aggregation was observed in patients with stable angina of effort (functional class I-II). Therefore, arginine can be recommended as an adjuvant in the treatment of patients with ischemic heart disease.

Endothelial cell repopulation after stenting determines in-stent neointima formation: effects of bare-metal vs. drug-eluting stents and genetic endothelial cell modification.

Science.gov (United States)

Douglas, Gillian; Van Kampen, Erik; Hale, Ashley B; McNeill, Eileen; Patel, Jyoti; Crabtree, Mark J; Ali, Ziad; Hoerr, Robert A; Alp, Nicholas J; Channon, Keith M

2013-11-01

Understanding endothelial cell repopulation post-stenting and how this modulates in-stent restenosis is critical to improving arterial healing post-stenting. We used a novel murine stent model to investigate endothelial cell repopulation post-stenting, comparing the response of drug-eluting stents with a primary genetic modification to improve endothelial cell function. Endothelial cell repopulation was assessed en face in stented arteries in ApoE(-/-) mice with endothelial-specific LacZ expression. Stent deployment resulted in near-complete denudation of endothelium, but was followed by endothelial cell repopulation, by cells originating from both bone marrow-derived endothelial progenitor cells and from the adjacent vasculature. Paclitaxel-eluting stents reduced neointima formation (0.423 ± 0.065 vs. 0.240 ± 0.040 mm(2), P = 0.038), but decreased endothelial cell repopulation (238 ± 17 vs. 154 ± 22 nuclei/mm(2), P = 0.018), despite complete strut coverage. To test the effects of selectively improving endothelial cell function, we used transgenic mice with endothelial-specific overexpression of GTP-cyclohydrolase 1 (GCH-Tg) as a model of enhanced endothelial cell function and increased NO production. GCH-Tg ApoE(-/-) mice had less neointima formation compared with ApoE(-/-) littermates (0.52 ± 0.08 vs. 0.26 ± 0.09 mm(2), P = 0.039). In contrast to paclitaxel-eluting stents, reduced neointima formation in GCH-Tg mice was accompanied by increased endothelial cell coverage (156 ± 17 vs. 209 ± 23 nuclei/mm(2), P = 0.043). Drug-eluting stents reduce not only neointima formation but also endothelial cell repopulation, independent of strut coverage. In contrast, selective targeting of endothelial cell function is sufficient to improve endothelial cell repopulation and reduce neointima formation. Targeting endothelial cell function is a rational therapeutic strategy to improve vascular healing and decrease neointima formation after stenting.

Altered decorin leads to disrupted endothelial cell function: a possible mechanism in the pathogenesis of fetal growth restriction?

Science.gov (United States)

Chui, A; Murthi, P; Gunatillake, T; Brennecke, S P; Ignjatovic, V; Monagle, P T; Whitelock, J M; Said, J M

2014-08-01

Fetal growth restriction (FGR) is a key cause of adverse pregnancy outcome where maternal and fetal factors are identified as contributing to this condition. Idiopathic FGR is associated with altered vascular endothelial cell functions. Decorin (DCN) has important roles in the regulation of endothelial cell functions in vascular environments. DCN expression is reduced in FGR. The objectives were to determine the functional consequences of reduced DCN in a human microvascular endothelial cell line model (HMVEC), and to determine downstream targets of DCN and their expression in primary placental microvascular endothelial cells (PLECs) from control and FGR-affected placentae. Short-interference RNA was used to reduce DCN expression in HMVECs and the effect on proliferation, angiogenesis and thrombin generation was determined. A Growth Factor PCR Array was used to identify downstream targets of DCN. The expression of target genes in control and FGR PLECs was performed. DCN reduction decreased proliferation and angiogenesis but increased thrombin generation with no effect on apoptosis. The array identified three targets of DCN: FGF17, IL18 and MSTN. Validation of target genes confirmed decreased expression of VEGFA, MMP9, EGFR1, IGFR1 and PLGF in HMVECs and PLECs from control and FGR pregnancies. Reduction of DCN in vascular endothelial cells leads to disrupted cell functions. The targets of DCN include genes that play important roles in angiogenesis and cellular growth. Therefore, differential expression of these may contribute to the pathogenesis of FGR and disease states in other microvascular circulations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Biosensor Technology Reveals the Disruption of the Endothelial Barrier Function and the Subsequent Death of Blood Brain Barrier Endothelial Cells to Sodium Azide and Its Gaseous Products.

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Kho, Dan T; Johnson, Rebecca H; O'Carroll, Simon J; Angel, Catherine E; Graham, E Scott

2017-09-21

Herein we demonstrate the sensitive nature of human blood-brain barrier (BBB) endothelial cells to sodium azide and its gaseous product. Sodium azide is known to be acutely cytotoxic at low millimolar concentrations, hence its use as a biological preservative (e.g., in antibodies). Loss of barrier integrity was noticed in experiments using Electric Cell-substrate Impedance Sensing (ECIS) biosensor technology, to measure endothelial barrier integrity continuously in real-time. Initially the effect of sodium azide was observed as an artefact where it was present in antibodies being employed in neutralisation experiments. This was confirmed where antibody clones that were azide-free did not mediate loss of barrier function. A delayed loss of barrier function in neighbouring wells implied the influence of a liberated gaseous product. ECIS technology demonstrated that the BBB endothelial cells had a lower level of direct sensitivity to sodium azide of ~3 µM. Evidence of gaseous toxicity was consistently observed at 30 µM and above, with disrupted barrier function and cell death in neighbouring wells. We highlight the ability of this cellular biosensor technology to reveal both the direct and gaseous toxicity mediated by sodium azide. The sensitivity and temporal dimension of ECIS technology was instrumental in these observations. These findings have substantial implications for the wide use of sodium azide in biological reagents, raising issues of their application in live-cell assays and with regard to the protection of the user. This research also has wider relevance highlighting the sensitivity of brain endothelial cells to a known mitochondrial disruptor. It is logical to hypothesise that BBB endothelial dysfunction due to mitochondrial dys-regulation could have an important but underappreciated role in a range of neurological diseases.

ROS-activated calcium signaling mechanisms regulating endothelial barrier function.

Science.gov (United States)

Di, Anke; Mehta, Dolly; Malik, Asrar B

2016-09-01

Increased vascular permeability is a common pathogenic feature in many inflammatory diseases. For example in acute lung injury (ALI) and its most severe form, the acute respiratory distress syndrome (ARDS), lung microvessel endothelia lose their junctional integrity resulting in leakiness of the endothelial barrier and accumulation of protein rich edema. Increased reactive oxygen species (ROS) generated by neutrophils (PMNs) and other inflammatory cells play an important role in increasing endothelial permeability. In essence, multiple inflammatory syndromes are caused by dysfunction and compromise of the barrier properties of the endothelium as a consequence of unregulated acute inflammatory response. This review focuses on the role of ROS signaling in controlling endothelial permeability with particular focus on ALI. We summarize below recent progress in defining signaling events leading to increased endothelial permeability and ALI. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chronic treatment with tadalafil improves endothelial function in men with increased cardiovascular risk.

Science.gov (United States)

Rosano, Giuseppe M C; Aversa, Antonio; Vitale, Cristiana; Fabbri, Andrea; Fini, Massimo; Spera, Giovanni

2005-02-01

Erectile dysfunction (ED) is often associated with a cluster of risk factors for coronary artery disease and reduced endothelial function. Acute and chronic administration of oral sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, improves endothelial function in patients with ED. Tadalafil (TAD) is a new PDE5 inhibitor with a long half life that allows alternate day administration. Aim of the study was to evaluate whether chronic therapy (4 weeks) with TAD improves endothelial function in patients with increased cardiovascular risk and whether this effect is sustained after discontinuation of therapy. We randomized 32 patients with increased cardiovascular risk to receive either TAD 20 mg on alternate days or matching placebo (PLB) for 4 weeks. Patients underwent evaluation of brachial artery flow-mediated dilation (FMD), nitrite/nitrate and endothelin-1 plasma levels at baseline, at the end of treatment period and after two-weeks follow-up. At 4 weeks, FMD was significantly improved by TAD (from 4.2+/-3.2 to 9.3+/-3.7%, p<0.01 vs. baseline), but was not modified by PLB (from 4.1+/-2.8 to 4.0+/-3.4%, p=NS). At 6 weeks the benefit in FMD was sustained in patients that received TAD (9.1+/-3.9% vs. 4.2+/-3.2%, p=0.01 vs. baseline; 9.1+/-3.9% vs. 9.3+/-3.7%, vs. 4 weeks, p=NS) while no changes in FMD were observed in patients randomized to PLB. Also, compared to baseline, a net increase in nitrite/nitrate levels (38.2+/-12.3 vs. 52.6+/-11.7 and 51.1+/-3.1, p<0.05) and a decrease in endothelin-1 levels (3.3+/-0.9 vs. 2.9.+/-0.7 and 2.9+/-0.9, p<0.05) was found both at four and six-weeks after TAD; these changes were inversely correlated as shown by regression analysis (adjusted R2=0.81, p<0.0001). Chronic therapy with TAD improves endothelial function in patients with increased cardiovascular risk regardless their degree of ED. The benefit of this therapy is sustained for at least two weeks after the discontinuation of therapy. Larger studies are needed in order

Time-course gene expression data on the transcriptional effects of Aminaphtone on ECV304 endothelial cells

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Giulia Salazar

2016-09-01

Full Text Available We previously showed that Aminaphtone, a drug used in the treatment of chronic venous insufficiency, modulates several vasoactive factors, such as endothelin-1 and adhesion molecules. Here, we provide data of time-course experiments about the effects of Aminaphtone on gene expression at the genome-wide level in human endothelial cells undergoing cytokine stimulation in vitro. ECV-304 endothelial cells were incubated with interleukin-1β (IL-1β in the presence or absence of Aminaphtone for 1, 3, and 6 h. Gene expression profiles were analyzed by microarray. This article contains complete data on the genes significantly modulated by the drug over time. The data are supplemental to our original research article reporting detailed analysis of the actions of Aminaphtone on IL-1β stimulated endothelial cells at the molecular level, ''Gene expression profiling reveals novel protective effects of Aminaphtone on ECV304 endothelial cells'' (Salazar et al., 2016 [1]. Chemical compound studied in this article: Aminaphtone (PubChem CID: 84621, Keywords: Endothelial cells, Transcriptome, Inflammation, Vasoactive drug

Differentiation of Human Pluripotent Stem Cells into Functional Endothelial Cells in Scalable Suspension Culture

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Ruth Olmer

2018-05-01

Full Text Available Summary: Endothelial cells (ECs are involved in a variety of cellular responses. As multifunctional components of vascular structures, endothelial (progenitor cells have been utilized in cellular therapies and are required as an important cellular component of engineered tissue constructs and in vitro disease models. Although primary ECs from different sources are readily isolated and expanded, cell quantity and quality in terms of functionality and karyotype stability is limited. ECs derived from human induced pluripotent stem cells (hiPSCs represent an alternative and potentially superior cell source, but traditional culture approaches and 2D differentiation protocols hardly allow for production of large cell numbers. Aiming at the production of ECs, we have developed a robust approach for efficient endothelial differentiation of hiPSCs in scalable suspension culture. The established protocol results in relevant numbers of ECs for regenerative approaches and industrial applications that show in vitro proliferation capacity and a high degree of chromosomal stability. : In this article, U. Martin and colleagues show the generation of hiPSC endothelial cells in scalable cultures in up to 100 mL culture volume. The generated ECs show in vitro proliferation capacity and a high degree of chromosomal stability after in vitro expansion. The established protocol allows to generate hiPSC-derived ECs in relevant numbers for regenerative approaches. Keywords: hiPSC differentiation, endothelial cells, scalable culture

Placental oxidative stress and maternal endothelial function in pregnant women with normotensive fetal growth restriction.

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Yoshida, Atsumi; Watanabe, Kazushi; Iwasaki, Ai; Kimura, Chiharu; Matsushita, Hiroshi; Wakatsuki, Akihiko

2018-04-01

The purpose of this study was to investigate the relationship between placental oxidative stress and maternal endothelial function in pregnant women with normotensive fetal growth restriction (FGR). We examined serum concentrations of oxygen free radicals (d-ROMs), maternal angiogenic factor (PlGF), and sFlt-1, placental oxidative DNA damage, and maternal endothelial function in 17 women with early-onset preeclampsia (PE), 18 with late-onset PE, 14 with normotensive FGR, and 21 controls. Flow-mediated vasodilation (FMD) was assessed as a marker of maternal endothelial function. Immunohistochemical analysis was performed to measure the proportion of placental trophoblast cell nuclei staining positive for 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage. Maternal serum d-ROM, sFlt-1 concentrations, and FMD did not significantly differ between the control and normotensive FGR groups. The proportion of nuclei staining positive for 8-OHdG was significantly higher in the normotensive FGR group relative to the control group. Our findings demonstrate that, despite the presence of placental oxidative DNA damage as observed in PE patients, pregnant women with normotensive FGR show no increase in the concentrations of sFlt-1 and d-ROMs, or a decrease in FMD.

Identification and functional analysis of endothelial tip cell-enriched genes.

Science.gov (United States)

del Toro, Raquel; Prahst, Claudia; Mathivet, Thomas; Siegfried, Geraldine; Kaminker, Joshua S; Larrivee, Bruno; Breant, Christiane; Duarte, Antonio; Takakura, Nobuyuki; Fukamizu, Akiyoshi; Penninger, Josef; Eichmann, Anne

2010-11-11

Sprouting of developing blood vessels is mediated by specialized motile endothelial cells localized at the tips of growing capillaries. Following behind the tip cells, endothelial stalk cells form the capillary lumen and proliferate. Expression of the Notch ligand Delta-like-4 (Dll4) in tip cells suppresses tip cell fate in neighboring stalk cells via Notch signaling. In DLL4(+/-) mouse mutants, most retinal endothelial cells display morphologic features of tip cells. We hypothesized that these mouse mutants could be used to isolate tip cells and so to determine their genetic repertoire. Using transcriptome analysis of retinal endothelial cells isolated from DLL4(+/-) and wild-type mice, we identified 3 clusters of tip cell-enriched genes, encoding extracellular matrix degrading enzymes, basement membrane components, and secreted molecules. Secreted molecules endothelial-specific molecule 1, angiopoietin 2, and apelin bind to cognate receptors on endothelial stalk cells. Knockout mice and zebrafish morpholino knockdown of apelin showed delayed angiogenesis and reduced proliferation of stalk cells expressing the apelin receptor APJ. Thus, tip cells may regulate angiogenesis via matrix remodeling, production of basement membrane, and release of secreted molecules, some of which regulate stalk cell behavior.

Endothelial microparticle-mediated transfer of MicroRNA-126 promotes vascular endothelial cell repair via SPRED1 and is abrogated in glucose-damaged endothelial microparticles.

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Jansen, Felix; Yang, Xiaoyan; Hoelscher, Marion; Cattelan, Arianna; Schmitz, Theresa; Proebsting, Sebastian; Wenzel, Daniela; Vosen, Sarah; Franklin, Bernardo S; Fleischmann, Bernd K; Nickenig, Georg; Werner, Nikos

2013-10-29

Repair of the endothelium after vascular injury is crucial for preserving endothelial integrity and preventing the development of vascular disease. The underlying mechanisms of endothelial cell repair are largely unknown. We sought to investigate whether endothelial microparticles (EMPs), released from apoptotic endothelial cells (ECs), influence EC repair. Systemic treatment of mice with EMPs after electric denudation of the endothelium accelerated reendothelialization in vivo. In vitro experiments revealed that EMP uptake in ECs promotes EC migration and proliferation, both critical steps in endothelial repair. To dissect the underlying mechanisms, Taqman microRNA array was performed, and microRNA (miR)-126 was identified as the predominantly expressed miR in EMPs. The following experiments demonstrated that miR-126 was transported into recipient human coronary artery endothelial cells by EMPs and functionally regulated the target protein sprouty-related, EVH1 domain-containing protein 1 (SPRED1). Knockdown of miR-126 in EMPs abrogated EMP-mediated effects on human coronary artery endothelial cell migration and proliferation in vitro and reendothelialization in vivo. Interestingly, after simulating diabetic conditions, EMPs derived from glucose-treated ECs contained significantly lower amounts of miR-126 and showed reduced endothelial repair capacity in vitro and in vivo. Finally, expression analysis of miR-126 in circulating microparticles from 176 patients with stable coronary artery disease with and without diabetes mellitus revealed a significantly reduced miR-126 expression in circulating microparticles from diabetic patients. Endothelial microparticles promote vascular endothelial repair by delivering functional miR-126 into recipient cells. In pathological hyperglycemic conditions, EMP-mediated miR-126-induced EC repair is altered.

Inhibition of protein kinase Cbeta does not improve endothelial function in type 2 diabetes.

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Beckman, Joshua A; Goldfine, Allison B; Goldin, Alison; Prsic, Adnan; Kim, Sora; Creager, Mark A

2010-08-01

Antagonism of protein kinase Cbeta (PKCbeta) restores endothelial function in experimental models of diabetes and prevents vascular dysfunction in response to hyperglycemia in healthy humans. We tested the hypothesis that PKCbeta antagonism would improve vascular function in subjects with type 2 diabetes compared with healthy control subjects. The effect of PKCbeta was evaluated in a randomized, placebo-controlled, double-blinded crossover trial. The study was performed in the outpatient setting of a university medical center. Thirteen subjects with type 2 diabetes without evidence of cardiovascular disease and 15 healthy control subjects were recruited via newspaper advertisement. Subjects underwent a randomized, double-blind, crossover, placebo-controlled trial of the selective PKCbeta antagonist ruboxistaurin mesylate. Subjects received each treatment for 14 d. Endothelium-dependent and endothelium-independent vasodilation of forearm resistance vessels was measured with mercury-in-silastic, strain-gauge plethysmography during intraarterial administration of methacholine chloride and verapamil, respectively. Markers of inflammation, fibrinolysis, endothelial damage, and oxidative stress were measured after each treatment. Endothelium-dependent vasodilation of forearm resistance vessels was attenuated in diabetic subjects when compared with healthy subjects (P=0.001). Endothelium-independent vasodilation did not differ between groups (P value not significant). Ruboxistaurin did not significantly change endothelium-dependent or endothelium-independent vasodilation or blood-based markers of inflammation, fibrinolysis, endothelial damage, and oxidative stress in either diabetic or healthy subjects. Endothelial dysfunction of forearm resistance vessels was not improved by 2 wk of selective PKCbeta inhibition in patients with diabetes. These results suggest that PKCbeta does not contribute significantly to vascular dysfunction in otherwise healthy patients with type 2

A biphasic endothelial stress-survival mechanism regulates the cellular response to vascular endothelial growth factor A

International Nuclear Information System (INIS)

Latham, Antony M.; Odell, Adam F.; Mughal, Nadeem A.; Issitt, Theo; Ulyatt, Clare; Walker, John H.; Homer-Vanniasinkam, Shervanthi; Ponnambalam, Sreenivasan

2012-01-01

Vascular endothelial growth factor A (VEGF-A) is an essential cytokine that regulates endothelial function and angiogenesis. VEGF-A binding to endothelial receptor tyrosine kinases such as VEGFR1 and VEGFR2 triggers cellular responses including survival, proliferation and new blood vessel sprouting. Increased levels of a soluble VEGFR1 splice variant (sFlt-1) correlate with endothelial dysfunction in pathologies such as pre-eclampsia; however the cellular mechanism(s) underlying the regulation and function of sFlt-1 are unclear. Here, we demonstrate the existence of a biphasic stress response in endothelial cells, using serum deprivation as a model of endothelial dysfunction. The early phase is characterized by a high VEGFR2:sFlt-1 ratio, which is reversed in the late phase. A functional consequence is a short-term increase in VEGF-A-stimulated intracellular signaling. In the late phase, sFlt-1 is secreted and deposited at the extracellular matrix. We hypothesized that under stress, increased endothelial sFlt-1 levels reduce VEGF-A bioavailability: VEGF-A treatment induces sFlt-1 expression at the cell surface and VEGF-A silencing inhibits sFlt-1 anchorage to the extracellular matrix. Treatment with recombinant sFlt-1 inhibits VEGF-A-stimulated in vitro angiogenesis and sFlt-1 silencing enhances this process. In this response, increased VEGFR2 levels are regulated by the phosphatidylinositol-3-kinase and PKB/Akt signaling pathways and increased sFlt-1 levels by the ERK1/2 signaling pathway. We conclude that during serum withdrawal, cellular sensing of environmental stress modulates sFlt-1 and VEGFR2 levels, regulating VEGF-A bioavailability and ensuring cell survival takes precedence over cell proliferation and migration. These findings may underpin an important mechanism contributing to endothelial dysfunction in pathological states. -- Highlights: ► Endothelial cells mount a stress response under conditions of low serum. ► Endothelial VEGFR levels are

EFFECT OF FUROSTANOL GLYCOSIDES FROM CULTURED DIOSCOREA DELTOIDEA CELLS ON REGULATORY FUNCTION OF ENDOTHELIUM IN A RAT MODEL OF HYPOESTROGEN-INDUCED ENDOTHELIAL DYSFUNCTION

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E. B. Artyushkova

2008-01-01

Full Text Available Aim. To study the effects of furostanol glycosides from cultured Dioscorea Deltoidea cells (DM-05, Institute of Plant Physiology, RAS on physiological and biochemical markers of endothelial function in rats with hypoestrogen-induced endothelial dysfunction.Material and methods. 10 female rats of Wistar line, with body mass 200-300 g have been included in the experiment. The bilateral ovariectomy was performed in rats to produce the model of hypoestrogen-induced endothelial dysfunction. Rats were treated with the injections of DM-05 during 6 weeks. False ovariectomy was performed in rats of control group (n=10.Results. DM-05 restored the levels of stable metabolites of nitric oxide (NO which reflex endothelial NO-synthase activity. Besides DM-05 corrected blood pressure and endothelial function. Experiments on open heart showed that DM-05 protects the cardiac tissue from hypoestrogen-induced hyperadrenoreactivity.Conclusion. Treatment with plant origin substances with estrogen-like activity can be a perspective approach to the correction of endothelial function and decrease in cardiovascular risk in menopause women.

Crocin Improves the Endothelial Function Regulated by Kca3.1 Through ERK and Akt Signaling Pathways

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Huike Yang

2018-03-01

Full Text Available Background/Aims: Based on the protective effect of crocin against cardiovascular diseases, we hypothesize that crocin could improve endothelial function through activating the eNOS(endothelial nitric oxide synthase /NO pathway and/or the intermediate-conductance Ca2+-activated K+ channels (KCa3.1. Methods: In this study, rat aortic rings were used to assess the regulatory effect of crocin on vascular tone and nitric oxide, prostacyclin, and KCa3.1, all endothelial vasodilators, were analyzed for effects by crocin. The expression profiles of p-eNOS, total-eNOS, p-ERK, total-ERK, p-Akt, total-Akt, KCa3.1, CD31, thrombomodulin, ICAM-1 and VCAM-1 were tested by western blotting. KCa3.1 was also analyzed by qPCR and immunofluorescence staining. Fluorescence and confocal microscopy were used to determine NO generation and intracellular Ca2+. Both EdU and MTT assays were used to evaluate cell viability. Cellular migration was assessed using transwell assay. Results: Crocin relaxed pre-contracted artery rings through either NO or KCa3.1, but not PGI, in an endothelium-dependent manner. Furthermore, crocin increased p-eNOS, total-eNOS expression and NO production as well as intracellular Ca2+ in both HUVECs and HUAECs (Human Umbilical Artery Endothelial cells. Crocin also stimulated the expression of CD31, thrombomodulin and vascular cell adhesion molecule 1 (VCAM-1, as well as increased cellular proliferation and migration in vitro. Interestingly, we determined for the first time that by blocking or silencing KCa3.1 there was inhibition of crocin induced upregulation of p-eNOS and total-eNOS. Correspondingly, the KCa3.1 inhibitor TRAM-34 also reduced the expression of CD31, thrombomodulin and VCAM-1, as well as diminished intracellular Ca2+, cellular proliferation and migration. Finally, crocin stimulated the expression of p-ERK, total-ERK, p-Akt and total-Akt, however suppression of MEK and Akt inhibited this expression profile in endothelial cells

Long-Term Functional and Anatomical Outcome after Descemet Stripping Automated Endothelial Keratoplasty: A Prospective Single-Center Study

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Jeroen van Rooij

2018-01-01

Full Text Available Purpose. To investigate the long-term anatomical and functional outcomes of Descemet stripping automated endothelial keratoplasty (DSAEK. Methods. Prospective follow-up of 114 eyes (95 subjects after DSAEK for endothelial dysfunction. Measurements included best spectacle-corrected visual acuity (BSCVA, straylight, endothelial cell density (ECD, and graft thickness. Results. The mean follow-up time was 5.1 ± 1.5 years. Four grafts ultimately failed (after 5 to 7 years. From baseline up to 1 year after DSAEK, mean BSCVA improved by 0.30 logMAR. This beneficial effect remained until the last follow-up (LFU. After DSAEK, straylight was reduced. ECD sharply dropped by 900 cells/mm2 (33% immediately after surgery and, thereafter, steadily decreased at a rate of 11 cells/mm2 per month. No significant correlation was observed between graft thickness at 3 years and BSCVA. Conclusions. We observed a low graft failure rate and a normalization of graft thickness. Postoperative straylight remained elevated relative to the normal population. The sharp initial and the subsequent more gradual ECD decline are consistent with other studies. A significant and prolonged functional gain can be achieved by posterior lamellar grafting for endothelial dysfunction.

The effects of dexamethasone on the Na,K-ATPase activity and pump function of corneal endothelial cells.

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Hatou, Shin; Yamada, Masakazu; Mochizuki, Hiroshi; Shiraishi, Atsushi; Joko, Takeshi; Nishida, Teruo

2009-05-01

The Na(+)- and K(+)-dependent ATPase (Na,K-ATPase) expressed in the basolateral membrane of corneal endothelial cells plays an important role in the pump function of the corneal endothelium. We investigated the possible role of dexamethasone in the regulation of Na,K-ATPase activity and pump function in corneal endothelial cells. Confluent monolayers of mouse corneal endothelial cells were exposed to dexamethasone. ATPase activity of the cells was evaluated by spectrophotometric measurement of phosphate released from ATP with the use of ammonium molybdate, with Na,K-ATPase activity being defined as the portion of total ATPase activity sensitive to ouabain. Pump function of the cells was measured with the use of an Ussing chamber, with the pump function attributable to Na,K-ATPase activity being defined as the portion of the total short-circuit current sensitive to ouabain. Western blot analysis was examined to measure the expression of the Na,K-ATPase alpha(1)-subunit. Dexamethasone (1 or 10 microM) increased the Na,K-ATPase activity and pump function of the cultured cells. These effects of dexamethasone were blocked by cycloheximide, a protein synthesis inhibitor. Western blot analysis also indicated that dexamethasone increased the expression of the Na,K-ATPase alpha(1)-subunit, whereas it decreased the expression of the phospho-Na,K-ATPase alpha(1)-subunit. Our results suggest that dexamethasone stimulates Na,K-ATPase activity in mouse corneal endothelial cells. The effect of dexamethasone activation in these cells is mediated by Na,K-ATPase synthesis and increase in an enzymatic activity by dephosphorylation of Na,K-ATPase alpha(1)-subunits.

Acute dark chocolate and cocoa ingestion and endothelial function: a randomized controlled crossover trial.

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Faridi, Zubaida; Njike, Valentine Yanchou; Dutta, Suparna; Ali, Ather; Katz, David L

2008-07-01

Studies suggest cardioprotective benefits of dark chocolate containing cocoa. This study examines the acute effects of solid dark chocolate and liquid cocoa intake on endothelial function and blood pressure in overweight adults. Randomized, placebo-controlled, single-blind crossover trial of 45 healthy adults [mean age: 53 y; mean body mass index (in kg/m(2)): 30]. In phase 1, subjects were randomly assigned to consume a solid dark chocolate bar (containing 22 g cocoa powder) or a cocoa-free placebo bar (containing 0 g cocoa powder). In phase 2, subjects were randomly assigned to consume sugar-free cocoa (containing 22 g cocoa powder), sugared cocoa (containing 22 g cocoa powder), or a placebo (containing 0 g cocoa powder). Solid dark chocolate and liquid cocoa ingestion improved endothelial function (measured as flow-mediated dilatation) compared with placebo (dark chocolate: 4.3 +/- 3.4% compared with -1.8 +/- 3.3%; P cocoa: 5.7 +/- 2.6% and 2.0 +/- 1.8% compared with -1.5 +/- 2.8%; P cocoa compared with placebo (dark chocolate: systolic, -3.2 +/- 5.8 mm Hg compared with 2.7 +/- 6.6 mm Hg; P cocoa: systolic, -2.1 +/- 7.0 mm Hg compared with 3.2 +/- 5.6 mm Hg; P cocoa (5.7 +/- 2.6% compared with 2.0 +/- 1.8%; P cocoa improved endothelial function and lowered blood pressure in overweight adults. Sugar content may attenuate these effects, and sugar-free preparations may augment them.

Establishment of functioning human corneal endothelial cell line with high growth potential.

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Tadashi Yokoi

Full Text Available Hexagonal-shaped human corneal endothelial cells (HCEC form a monolayer by adhering tightly through their intercellular adhesion molecules. Located at the posterior corneal surface, they maintain corneal translucency by dehydrating the corneal stroma, mainly through the Na(+- and K(+-dependent ATPase (Na(+/K(+-ATPase. Because HCEC proliferative activity is low in vivo, once HCEC are damaged and their numbers decrease, the cornea begins to show opacity due to overhydration, resulting in loss of vision. HCEC cell cycle arrest occurs at the G1 phase and is partly regulated by cyclin-dependent kinase inhibitors (CKIs in the Rb pathway (p16-CDK4/CyclinD1-pRb. In this study, we tried to activate proliferation of HCEC by inhibiting CKIs. Retroviral transduction was used to generate two new HCEC lines: transduced human corneal endothelial cell by human papillomavirus type E6/E7 (THCEC (E6/E7 and transduced human corneal endothelial cell by Cdk4R24C/CyclinD1 (THCEH (Cyclin. Reverse transcriptase polymerase chain reaction analysis of gene expression revealed little difference between THCEC (E6/E7, THCEH (Cyclin and non-transduced HCEC, but cell cycle-related genes were up-regulated in THCEC (E6/E7 and THCEH (Cyclin. THCEH (Cyclin expressed intercellular molecules including ZO-1 and N-cadherin and showed similar Na(+/K(+-ATPase pump function to HCEC, which was not demonstrated in THCEC (E6/E7. This study shows that HCEC cell cycle activation can be achieved by inhibiting CKIs even while maintaining critical pump function and morphology.

Venous hemodynamic changes in lower limb venous disease

DEFF Research Database (Denmark)

Lee, Byung Boong; Nicolaides, Andrew N; Myers, Kenneth

2016-01-01

). Their aim was to confirm or dispel long-held hemodynamic principles and to provide a comprehensive review of venous hemodynamic concepts underlying the pathophysiology of lower limb venous disorders, their usefulness for investigating patients and the relevant hemodynamic changes associated with various...... forms of treatment. Chapter 1 is devoted to basic hemodynamic concepts and normal venous physiology. Chapter 2 presents the mechanism and magnitude of hemodynamic changes in acute deep vein thrombosis indicating their pathophysiological and clinical significance. Chapter 3 describes the hemodynamic...... changes that occur in different classes of chronic venous disease and their relation to the anatomic extent of disease in the macrocirculation and microcirculation. The next four chapters (Chapters 4-7) describe the hemodynamic changes resulting from treatment by compression using different materials...

A fish-based diet intervention improves endothelial function in postmenopausal women with type 2 diabetes mellitus: a randomized crossover trial.

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Kondo, Keiko; Morino, Katsutaro; Nishio, Yoshihiko; Kondo, Motoyuki; Nakao, Keiko; Nakagawa, Fumiyuki; Ishikado, Atsushi; Sekine, Osamu; Yoshizaki, Takeshi; Kashiwagi, Atsunori; Ugi, Satoshi; Maegawa, Hiroshi

2014-07-01

The beneficial effects of fish and n-3 polyunsaturated fatty acids (PUFAs) consumption on atherosclerosis have been reported in numerous epidemiological studies. However, to the best of our knowledge, the effects of a fish-based diet intervention on endothelial function have not been investigated. Therefore, we studied these effects in postmenopausal women with type 2 diabetes mellitus (T2DM). Twenty-three postmenopausal women with T2DM were assigned to two four-week periods of either a fish-based diet (n-3 PUFAs ≧ 3.0 g/day) or a control diet in a randomized crossover design. Endothelial function was measured with reactive hyperemia using strain-gauge plethysmography and compared with the serum levels of fatty acids and their metabolites. Endothelial function was determined with peak forearm blood flow (Peak), duration of reactive hyperemia (Duration) and flow debt repayment (FDR). A fish-based dietary intervention improved Peak by 63.7%, Duration by 27.9% and FDR by 70.7%, compared to the control diet. Serum n-3 PUFA levels increased after the fish-based diet period and decreased after the control diet, compared with the baseline (1.49 vs. 0.97 vs. 1.19 mmol/l, p diet intervention, possibly due to the inhibition of the activity of soluble epoxide hydrolase. A fish-based dietary intervention improves endothelial function in postmenopausal women with T2DM. Dissociation between the serum n-3 PUFA concentration and endothelial function suggests that the other factors may contribute to this phenomenon. Copyright © 2014 Elsevier Inc. All rights reserved.

Endothelial mineralocorticoid receptor activation mediates endothelial dysfunction in diet-induced obesity.

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Schäfer, Nicola; Lohmann, Christine; Winnik, Stephan; van Tits, Lambertus J; Miranda, Melroy X; Vergopoulos, Athanasios; Ruschitzka, Frank; Nussberger, Jürg; Berger, Stefan; Lüscher, Thomas F; Verrey, François; Matter, Christian M

2013-12-01

Aldosterone plays a crucial role in cardiovascular disease. 'Systemic' inhibition of its mineralocorticoid receptor (MR) decreases atherosclerosis by reducing inflammation and oxidative stress. Obesity, an important cardiovascular risk factor, is an inflammatory disease associated with increased plasma aldosterone levels. We have investigated the role of the 'endothelial' MR in obesity-induced endothelial dysfunction, the earliest stage in atherogenesis. C57BL/6 mice were exposed to a normal chow diet (ND) or a high-fat diet (HFD) alone or in combination with the MR antagonist eplerenone (200 mg/kg/day) for 14 weeks. Diet-induced obesity impaired endothelium-dependent relaxation in response to acetylcholine, whereas eplerenone treatment of obese mice prevented this. Expression analyses in aortic endothelial cells isolated from these mice revealed that eplerenone attenuated expression of pro-oxidative NADPH oxidase (subunits p22phox, p40phox) and increased expression of antioxidative genes (glutathione peroxidase-1, superoxide dismutase-1 and -3) in obesity. Eplerenone did not affect obesity-induced upregulation of cyclooxygenase (COX)-1 or prostacyclin synthase. Endothelial-specific MR deletion prevented endothelial dysfunction in obese (exhibiting high 'endogenous' aldosterone) and in 'exogenous' aldosterone-infused lean mice. Pre-incubation of aortic rings from aldosterone-treated animals with the COX-inhibitor indomethacin restored endothelial function. Exogenous aldosterone administration induced endothelial expression of p22phox in the presence, but not in the absence of the endothelial MR. Obesity-induced endothelial dysfunction depends on the 'endothelial' MR and is mediated by an imbalance of oxidative stress-modulating mechanisms. Therefore, MR antagonists may represent an attractive therapeutic strategy in the increasing population of obese patients to decrease vascular dysfunction and subsequent atherosclerotic complications.

Intracavernous Delivery of a Designed Angiopoietin-1 Variant Rescues Erectile Function by Enhancing Endothelial Regeneration in the Streptozotocin-Induced Diabetic Mouse

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Jin, Hai-Rong; Kim, Woo Jean; Song, Jae Sook; Piao, Shuguang; Choi, Min Ji; Tumurbaatar, Munkhbayar; Shin, Sun Hwa; Yin, Guo Nan; Koh, Gou Young; Ryu, Ji-Kan; Suh, Jun-Kyu

2011-01-01

OBJECTIVE Patients with diabetic erectile dysfunction often have severe endothelial dysfunction and respond poorly to oral phosphodiesterase-5 inhibitors. We examined the effectiveness of the potent angiopoietin-1 (Ang1) variant, cartilage oligomeric matrix protein (COMP)-Ang1, in promoting cavernous endothelial regeneration and restoring erectile function in diabetic animals. RESEARCH DESIGN AND METHODS Four groups of mice were used: controls; streptozotocin (STZ)-induced diabetic mice; STZ-induced diabetic mice treated with repeated intracavernous injections of PBS; and STZ-induced diabetic mice treated with COMP-Ang1 protein (days −3 and 0). Two and 4 weeks after treatment, we measured erectile function by electrical stimulation of the cavernous nerve. The penis was harvested for histologic examinations, Western blot analysis, and cGMP quantification. We also performed a vascular permeability test. RESULTS Local delivery of the COMP-Ang1 protein significantly increased cavernous endothelial proliferation, endothelial nitric oxide (NO) synthase (NOS) phosphorylation, and cGMP expression compared with that in the untreated or PBS-treated STZ-induced diabetic group. The changes in the group that received COMP-Ang1 restored erectile function up to 4 weeks after treatment. Endothelial protective effects, such as marked decreases in the expression of p47phox and inducible NOS, in the generation of superoxide anion and nitrotyrosine, and in the number of apoptotic cells in the corpus cavernosum tissue, were noted in COMP-Ang1–treated STZ-induced diabetic mice. An intracavernous injection of COMP-Ang1 completely restored endothelial cell-cell junction proteins and decreased cavernous endothelial permeability. COMP-Ang1–induced promotion of cavernous angiogenesis and erectile function was abolished by the NOS inhibitor, N-nitro-L-arginine methyl ester, but not by the NADPH oxidase inhibitor, apocynin. CONCLUSIONS These findings support the concept of cavernous

The acute effect of coffee on endothelial function and glucose metabolism following a glucose load in healthy human volunteers.

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Boon, Evan A J; Croft, Kevin D; Shinde, Sujata; Hodgson, Jonathan M; Ward, Natalie C

2017-09-20

A diet rich in plant polyphenols has been suggested to reduce the incidence of cardiovascular disease and type 2 diabetes mellitus, in part, via improvements in endothelial function. Coffee is a rich source of phenolic compounds including the phenolic acid, chlorogenic acid (CGA). The aim of the study was to investigate the effect of coffee as a whole beverage on endothelial function, blood pressure and blood glucose concentration. Twelve healthy men and women were recruited to a randomised, placebo-controlled, cross-over study, with three treatments tested: (i) 18 g of ground caffeinated coffee containing 300 mg CGA in 200 mL of hot water, (ii) 18 g of decaffeinated coffee containing 287 mg CGA in 200 mL of hot water, and (iii) 200 mL of hot water (control). Treatment beverages were consumed twice, two hours apart, with the second beverage consumed simultaneously with a 75 g glucose load. Blood pressure was recorded and the finger prick glucose test was performed at time = 0 and then every 30 minutes up to 2 hours. Endothelial function, assessed using flow-mediated dilatation (FMD) of the brachial artery, was measured at 1 hour and a blood sample taken at 2 hours to measure plasma nitrate/nitrite and 5-CGA concentrations. The FMD response was significantly higher in the caffeinated coffee group compared to both decaffeinated coffee and water groups (P coffee and water. Blood glucose concentrations and blood pressure were not different between the three treatment groups. In conclusion, the consumption of caffeinated coffee resulted in a significant improvement in endothelial function, but there was no evidence for benefit regarding glucose metabolism or blood pressure. Although the mechanism has yet to be elucidated the results suggest that coffee as a whole beverage may improve endothelial function, or that caffeine is the component of coffee responsible for improving FMD.

Metformin Improves Endothelial Function and Reduces Blood Pressure in Diabetic Spontaneously Hypertensive Rats Independent from Glycemia Control : Comparison to Vildagliptin

NARCIS (Netherlands)

Hamidi Shishavan, Mahdi; Henning, Robert H; van Buiten, Azuwerus; Goris, Maaike; Deelman, Leo E; Buikema, Hendrik

2017-01-01

Metformin confers vascular benefits beyond glycemia control, possibly via pleiotropic effects on endothelial function. In type-1-diabetes-mellitus (T1DM-)patients metformin improved flow-mediated dilation but also increased prostaglandin(PG)-F-2 alpha, a known endothelial-contracting factor. To

Resveratrol Treatment Normalizes the Endothelial Function and Blood Pressure in Ovariectomized Rats.

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Fabricio, Victor; Oishi, Jorge Camargo; Biffe, Bruna Gabriele; Ruffoni, Leandro Dias Gonçalves; Silva, Karina Ana da; Nonaka, Keico Okino; Rodrigues, Gerson Jhonatan

2017-02-01

Despite knowing that resveratrol has effects on blood vessels, blood pressure and that phytostrogens can also improve the endothelium-dependent relaxation/vasodilation, there are no reports of reveratrol's direct effect on the endothelial function and blood pressure of animals with estrogen deficit (mimicking post-menopausal increased blood pressure). To verify the effect of two different periods of preventive treatment with resveratrol on blood pressure and endothelial function in ovariectomized young adult rats. 3-month old female Wistar rats were used and distributed in 6 groups: intact groups with 60 or 90 days, ovariectomized groups with 60 or 90 days, and ovariectomized treated with resveratrol (10 mg/kg of body weight per day) for 60 or 90 days. The number of days in each group corresponds to the duration of the experimental period. Vascular reactivity study was performed in abdominal aortic rings, systolic blood pressure was measured and serum nitric oxide (NO) concentration was quantified. Ovariectomy induced blood pressure increase 60 and 90 days after surgery, whereas the endothelial function decreased only 90 days after surgery, with no difference in NO concentration among the groups. Only longer treatment (90 days) with resveratrol was able to improve the endothelial function and normalize blood pressure. Our results suggest that 90 days of treatment with resveratrol is able to improve the endothelial function and decrease blood pressure in ovariectomized rats. Apesar de se saber que o resveratrol apresenta efeitos sobre a pressão arterial e os vasos sanguíneos, e que os fitoestrógenos podem melhorar o relaxamento/vasodilatação dependente do endotélio, não há relatos do efeito direto do resveratrol sobre a pressão arterial e a função endotelial em animais com deficiência de estrógeno (mimetizando a pressão arterial aumentada pós-menopausa). Verificar o efeito de dois diferentes períodos de tratamento preventivo com resveratrol sobre a

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

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Toque, Haroldo A; Nunes, Kenia P; Yao, Lin; Xu, Zhimin; Kondrikov, Dmitry; Su, Yunchao; Webb, R Clinton; Caldwell, Ruth B; Caldwell, R William

2013-01-01

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.

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

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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.

Metoprolol compared to carvedilol deteriorates insulin-stimulated endothelial function in patients with type 2 diabetes - a randomized study

DEFF Research Database (Denmark)

Kveiborg, Britt; Hermann, Thomas S; Major-Pedersen, Atheline

2010-01-01

Studies of beta blockade in patients with type 2 diabetes have shown inferiority of metoprolol treatment compared to carvedilol on indices of insulin resistance. The aim of this study was to examine the effect of metoprolol versus carvedilol on endothelial function and insulin-stimulated endothel......Studies of beta blockade in patients with type 2 diabetes have shown inferiority of metoprolol treatment compared to carvedilol on indices of insulin resistance. The aim of this study was to examine the effect of metoprolol versus carvedilol on endothelial function and insulin...

Investigation of cerebral venous outflow in microgravity.

Science.gov (United States)

Taibi, A; Gadda, G; Gambaccini, M; Menegatti, E; Sisini, F; Zamboni, P

2017-10-31

The gravitational gradient is the major component to face when considering the physiology of venous return, and there is a growing interest in understanding the mechanisms ensuring the heart filling, in the absence of gravity, for astronauts who perform long-term space missions. The purpose of the Drain Brain project was to monitor the cerebral venous outflow of a crew member during an experiment on the International Space Station (ISS), so as to study the compensatory mechanisms that facilitate this essential physiological action in subjects living in a microgravity environment. Such venous function has been characterized by means of a novel application of strain-gauge plethysmography which uses a capacitive sensor. In this contribution, preliminary results of our investigation have been presented. In particular, comparison of plethysmography data confirmed that long duration spaceflights lead to a redistribution of venous blood volume, and showed interesting differences in the amplitude of cardiac oscillations measured at the level of the neck veins. The success of the experiment has also demonstrated that thanks to its easy portability, non-invasiveness, and non-operator dependence, the proposed device can be considered as a novel tool for use aboard the ISS. Further trials are now under way to complete the investigation on the drainage function of the neck veins in microgravity.

Comparison of arterial and venous blood biomarker levels in chronic obstructive pulmonary disease [v1; ref status: indexed, http://f1000r.es/9x

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Emer Kelly

2013-04-01

Full Text Available Purpose: The development of novel biomarkers is an unmet need in chronic obstructive pulmonary disease (COPD. Arterial blood comes directly from the lung and venous blood drains capillary beds of the organ or tissue supplied. We hypothesized that there would be a difference in levels of the biomarkers metalloproteinase 9 (MMP-9, vascular endothelial growth factor A (VEGF-A and interleukin 6 (IL-6 in arterial compared with venous blood.  Methods: Radial artery and brachial vein blood samples were taken simultaneously in each of 12 patients with COPD and seven controls with normal lung function. Circulating immunoreactive MMP-9, VEGF-A and IL-6 levels in serum were measured using quantitative enzyme-linked immunosorbent assays. Results were compared using a Student’s paired t test. The study was powered to determine whether significant differences in cytokine levels were present between paired arterial and venous blood samples.   Results: In the 12 patients with COPD, four were female, and age ranged 53-85 years, mean age 69 years. Three patients in the control group were female, with age range 46-84 years, mean age 64.7 years. In the COPD group, three patients had mild, five moderate and four severe COPD. No significant difference was found between arterial and venous levels of MMP-9, VEGF-A or IL-6.  Conclusions: In this pilot study, levels of the measured biomarkers in arterial compared with venous blood in both COPD patients and healthy controls did not differ. This suggests that as we continue to chase the elusive biomarker in COPD as a potential tool to measure disease activity, we should focus on venous blood for this purpose.

Impact of an endothelial progenitor cell capturing stent on coronary microvascular function: comparison with drug-eluting stents.

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Choi, Woong Gil; Kim, Soo Hyun; Yoon, Hyung Seok; Lee, Eun Joo; Kim, Dong Woon

2015-01-01

Although drug-eluting stents (DESs) effectively reduce restenosis following percutaneous coronary intervention (PCI), they also delay re-endothelialization and impair microvascular function, resulting in adverse clinical outcomes. Endothelial progenitor cell (EPC) capturing stents, by providing a functional endothelial layer on the stent, have beneficial effects on microvascular function. However, data on coronary microvascular function in patients with EPC stents versus DESs are lacking. Seventy-four patients who previously underwent PCI were enrolled in this study. Microvascular function was evaluated 6 months after PCI based on the index of microvascular resistance (IMR) and the coronary flow reserve (CFR). IMR was calculated as the ratio of the mean distal coronary pressure at maximal hyperemia to the inverse of the hyperemic mean transit time (hTmn). The CFR was calculated by dividing the hTmn by the baseline mean transit time. Twenty-one patients (age, 67.2 ± 9.6 years; male:female, 15:6) with an EPC stent and 53 patients (age, 61.5 ± 14.7 years; male:female, 40:13) with second-generation DESs were included in the study. There were no significant differences in the baseline clinical and angiographic characteristics of the two groups. Angiography performed 6 months postoperatively did not show significant differences in their CFR values. However, patients with the EPC stent had a significantly lower IMR than patients with second-generation DESs (median, 25.5 [interquartile range, 12.85 to 28.18] vs. 29.0 [interquartile range, 15.42 to 39.23]; p = 0.043). Microvascular dysfunction was significantly improved after 6 months in patients with EPC stents compared to those with DESs. The complete re-endothelialization achieved with the EPC stent may provide clinical benefits over DESs, especially in patients with microvascular dysfunction.

Direct venous thrombolysis and venous angioplasty in the upper extremity

International Nuclear Information System (INIS)

Hollmann, J.P.; Guenther, R.W.

1987-01-01

Venous thromboses of stenoses in the upper extremity are often the result of a compression syndrome of the shoulder girdle, the Paget-von Schroetter syndrome, vascular surgery, space-occupying lesions in the mediastinum or the result of catheterisation. Direct venous thrombolysis and venous angioplasty were performed successfully in six patients. (orig.) [de

Vascular endothelial cell function and cardiovascular risk factors in patients with chronic renal failure

DEFF Research Database (Denmark)

Haaber, A B; Eidemak, I; Jensen, T

1995-01-01

Cardiovascular risk factors and markers of endothelial cell function were studied in nondiabetic patients with mild to moderate chronic renal failure. The transcapillary escape rate of albumin and the plasma concentrations of von Willebrand factor, fibrinogen, and plasma lipids were measured in 29...

Analysis of the vertebral venous system in relation to cerebral venous drainage on MR angiography

International Nuclear Information System (INIS)

Baik, Seung Kug; Sohn, Chul Ho; Kim, Gab Chul; Kim, Yong Sun

2004-01-01

In the supine position, cerebral venous drainage occurs primarily through the internal jugular veins, as seen on venous phase cerebral angiography. However, in the erect position, the vertebral venous system represents the major alternative pathway of cerebral venous drainage, while outflow through the internal jugular veins is absent or negligible. The purpose of this study is to evaluate the vertebral venous system and its relationship between the surrounding venous structures using magnetic resonance angiography (MRA) in the case of subjects in the supine position. We retrospectively reviewed the results of 65 patients (M:F = 31: 34, mean age 61.6 years) who underwent multi-phase contrast-enhanced carotid MRA. The imaging studies were performed using a 3.0 T MR unit (TR: 5.2, TE: 1.1, FA: 20, 3.8 thickness, EC: 1). We analyzed the appearance and extent of the vertebral venous system (vertebral venous plexus and vertebral artery venous plexus) and the internal jugular vein on the venous phase images. We also evaluated the main drainage pattern of the cerebral venous drainage and the drainage pattern of the vertebral venous system. The visualized vertebral venous system was defined as either poor, vertebral venous plexus dominant, vertebral artery venous plexus dominant or mixed. In the vertebral venous system, the vertebral artery venous plexus was visualized in 54 cases (83%). The appearance of the visualized vertebral artery venous plexus was symmetrical in 39 cases (72%) and asymmetrical in 15 cases (28%). The extent of the visualized vertebral artery venous plexus was partial in 26 cases (48%) and complete in 28 cases (52%). The vertebral venous plexus was visualized in 62 cases (95%). The appearance of the visualized vertebral artery venous plexus was symmetrical in 43 cases (69%) and asymmetrical in 19 cases (31%). The extent of the visualized vertebral artery venous plexus was partial in 35 cases (56%) and complete in 27 cases (44%). The appearance of the

Effect of pistachio diet on lipid parameters, endothelial function, inflammation, and oxidative status: a prospective study.

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Sari, Ibrahim; Baltaci, Yasemin; Bagci, Cahit; Davutoglu, Vedat; Erel, Ozcan; Celik, Hakim; Ozer, Orhan; Aksoy, Nur; Aksoy, Mehmet

2010-04-01

Recent studies have suggested that nuts have favorable effects beyond lipid lowering. We aimed to investigate effect of the Antep pistachio (Pistacia vera L.) on blood glucose, lipid parameters, endothelial function, inflammation, and oxidation in healthy young men living in a controlled environment. A Mediterranean diet was administered to normolipidemic 32 healthy young men (mean age 22 y, range 21-24) for 4 wk. After 4 wk, participants continued to receive the Mediterranean diet but pistachio was added for 4 wk by replacing the monounsaturated fat content constituting approximately 20% of daily caloric intake. Fasting blood samples and brachial endothelial function measurements were performed at baseline and after each diet. Compared with the Mediterranean diet, the pistachio diet decreased glucose (Ppistachio diet significantly improved endothelium-dependent vasodilation (P=0.002, 30% relative increase), decreased serum interleukin-6, total oxidant status, lipid hydroperoxide, and malondialdehyde and increased superoxide dismutase (Ppistachio diet improved blood glucose level, endothelial function, and some indices of inflammation and oxidative status in healthy young men. These findings are in accordance with the idea that nuts, in particular pistachio nuts, have favorable effects beyond lipid lowering that deserve to be evaluated with prospective follow-up studies. Copyright 2010. Published by Elsevier Inc.

Assessment of endothelial function and myocardial flow reserve using 15O-water PET without attenuation correction

International Nuclear Information System (INIS)

Tuffier, Stephane; Joubert, Michael; Bailliez, Alban; Legallois, Damien; Belin, Annette; Redonnet, Michel; Agostini, Denis; Manrique, Alain

2016-01-01

Myocardial blood flow (MBF) measurement using positron emission tomography (PET) from the washout rate of 15 O-water is theoretically independent of tissue attenuation. The aim of this study was to evaluate the impact of not using attenuation correction in the assessment of coronary endothelial function and myocardial flow reserve (MFR) using 15 O-water PET. We retrospectively processed 70 consecutive 15 O-water PET examinations obtained at rest and during cold pressor testing (CPT) in patients with dilated cardiomyopathy (n = 58), or at rest and during adenosine infusion in heart transplant recipients (n = 12). Data were reconstructed with attenuation correction (AC) and without attenuation correction (NAC) using filtered backprojection, and MBF was quantified using a single compartmental model. The agreement between AC and NAC data was assessed using Lin's concordance correlation coefficient followed by Bland-Altman plot analysis. Regarding endothelial function, NAC PET showed poor reproducibility and poor agreement with AC PET data. Conversely, NAC PET demonstrated high reproducibility and a strong agreement with AC PET for the assessment of MFR. Non-attenuation-corrected 15 O-water PET provided an accurate measurement of MFR compared to attenuation-corrected PET. However, non-attenuation-corrected PET data were less effective for the assessment of endothelial function using CPT in this population. (orig.)

Cilostazol activates function of bone marrow-derived endothelial progenitor cell for re-endothelialization in a carotid balloon injury model.

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Rie Kawabe-Yako

Full Text Available BACKGROUND: Cilostazol(CLZ has been used as a vasodilating anti-platelet drug clinically and demonstrated to inhibit proliferation of smooth muscle cells and effect on endothelial cells. However, the effect of CLZ on re-endothelialization including bone marrow (BM-derived endothelial progenitor cell (EPC contribution is unclear. We have investigated the hypothesis that CLZ might accelerate re-endothelialization with EPCs. METHODOLOGY/PRINCIPAL FINDINGS: Balloon carotid denudation was performed in male Sprague-Dawley rats. CLZ group was given CLZ mixed feed from 2 weeks before carotid injury. Control group was fed normal diet. CLZ accelerated re-endothelialization at 2 weeks after surgery and resulted in a significant reduction of neointima formation 4 weeks after surgery compared with that in control group. CLZ also increased the number of circulating EPCs throughout the time course. We examined the contribution of BM-derived EPCs to re-endothelialization by BM transplantation from Tie2/lacZ mice to nude rats. The number of Tie2-regulated X-gal positive cells on injured arterial luminal surface was increased at 2 weeks after surgery in CLZ group compared with that in control group. In vitro, CLZ enhanced proliferation, adhesion and migration activity, and differentiation with mRNA upregulation of adhesion molecule integrin αvβ3, chemokine receptor CXCR4 and growth factor VEGF assessed by real-time RT-PCR in rat BM-derived cultured EPCs. In addition, CLZ markedly increased the expression of SDF-1α that is a ligand of CXCR4 receptor in EPCs, in the media following vascular injury. CONCLUSIONS/SIGNIFICANCE: CLZ promotes EPC mobilization from BM and EPC recruitment to sites of arterial injury, and thereby inhibited neointima formation with acceleration of re-endothelialization with EPCs as well as pre-existing endothelial cells in a rat carotid balloon injury model. CLZ could be not only an anti-platelet agent but also a promising tool for

One Minute of Marijuana Secondhand Smoke Exposure Substantially Impairs Vascular Endothelial Function.

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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.

Early thrombus removal strategies for acute deep venous thrombosis: clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum.

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Meissner, Mark H; Gloviczki, Peter; Comerota, Anthony J; Dalsing, Michael C; Eklof, Bo G; Gillespie, David L; Lohr, Joann M; McLafferty, Robert B; Murad, M Hassan; Padberg, Frank; Pappas, Peter; Raffetto, Joseph D; Wakefield, Thomas W

2012-05-01

The anticoagulant treatment of acute deep venous thrombosis (DVT) has been historically directed toward the prevention of recurrent venous thromboembolism. However, such treatment imperfectly protects against late manifestations of the postthrombotic syndrome. By restoring venous patency and preserving valvular function, early thrombus removal strategies can potentially decrease postthrombotic morbidity. A committee of experts in venous disease was charged by the Society for Vascular Surgery and the American Venous Forum to develop evidence-based practice guidelines for early thrombus removal strategies, including catheter-directed pharmacologic thrombolysis, pharmacomechanical thrombolysis, and surgical thrombectomy. Evidence-based recommendations are based on a systematic review and meta-analysis of the relevant literature, supplemented when necessary by less rigorous data. Recommendations are made according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, incorporating the strength of the recommendation (strong: 1; weak: 2) and an evaluation of the level of the evidence (A to C). On the basis of the best evidence currently available, we recommend against routine use of the term "proximal venous thrombosis" in favor of more precise characterization of thrombi as involving the iliofemoral or femoropopliteal venous segments (Grade 1A). We further suggest the use of early thrombus removal strategies in ambulatory patients with good functional capacity and a first episode of iliofemoral DVT of venous outflow obstruction (Grade 1A). We suggest pharmacomechanical strategies over catheter-directed pharmacologic thrombolysis alone if resources are available and that surgical thrombectomy be considered if thrombolytic therapy is contraindicated (Grade 2C). Most data regarding early thrombus removal strategies are of low quality but do suggest patient-important benefits with respect to reducing postthrombotic morbidity. We

Favorable effects of concord grape juice on endothelial function and arterial stiffness in healthy smokers.

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Siasos, Gerasimos; Tousoulis, Dimitris; Kokkou, Eleni; Oikonomou, Evangelos; Kollia, Maria-Eleni; Verveniotis, Aleksis; Gouliopoulos, Nikolaos; Zisimos, Konstantinos; Plastiras, Aris; Maniatis, Konstantinos; Stefanadis, Christodoulos

2014-01-01

Smoking is associated with impaired vascular function. Concord grape juice (CGJ), a rich source of flavonoids, can modify cardiovascular risk factors. Endothelial function and arterial stiffness are surrogate markers of arterial health. We examined the impact of CGJ on arterial wall properties in healthy smokers. We studied the effect of a 2-week oral treatment with CGJ in 26 healthy smokers on 3 occasions (day 0 (baseline), day 7, and day 14) in a randomized, placebo-controlled, double-blind, crossover study. Measurements were taken before (pSm), immediately after (Sm0), and 20 minutes after (Sm20) cigarette smoking. Endothelial function was evaluated by flow-mediated dilation (FMD) of the brachial artery. Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness. Compared with placebo, treatment with CGJ resulted in a significant improvement in pSm values of FMD (P = 0.02) and PWV (P = 0.04). At baseline, smoking decreased FMD in both the CGJ group (P FMD on day 7 (P = 0.02) and day 14 (P < 0.001). Moreover, at baseline, smoking induced a significant elevation in PWV in both the CGJ group (P = 0.02) and the placebo group (P = 0.04). Treatment with CGJ prevented the smoking-induced elevation in PWV on day 7 (P = 0.003) and day 14 (P < 0.001). CGJ consumption improved endothelial function and vascular elastic properties of the arterial tree in healthy smokers and attenuated acute smoking-induced impairment of arterial wall properties.

Comparative evaluation of the impact on endothelial cells induced by different nanoparticle structures and functionalization

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Lisa Landgraf

2015-01-01

Full Text Available In the research field of nanoparticles, many studies demonstrated a high impact of the shape, size and surface charge, which is determined by the functionalization, of nanoparticles on cell viability and internalization into cells. This work focused on the comparison of three different nanoparticle types to give a better insight into general rules determining the biocompatibility of gold, Janus and semiconductor (quantum dot nanoparticles. Endothelial cells were subject of this study, since blood is the first barrier after intravenous nanoparticle application. In particular, stronger effects on the viability of endothelial cells were found for nanoparticles with an elongated shape in comparison to spherical ones. Furthermore, a positively charged nanoparticle surface (NH2, CyA leads to the strongest reduction in cell viability, whereas neutral and negatively charged nanoparticles are highly biocompatible to endothelial cells. These findings are attributed to a rapid internalization of the NH2-functionalized nanoparticles in combination with the damage of intracellular membranes. Interestingly, the endocytotic pathway seems to be a size-dependent process whereas nanoparticles with a size of 20 nm are internalized by caveolae-mediated endocytosis and nanoparticles with a size of 40 nm are taken up by clathrin-mediated internalization and macropinocytosis. Our results can be summarized to formulate five general rules, which are further specified in the text and which determine the biocompatibility of nanoparticles on endothelial cells. Our findings will help to design new nanoparticles with optimized properties concerning biocompatibility and uptake behavior with respect to the respective intended application.

Mechanical Adaptability of the MMP-Responsive Film Improves the Functionality of Endothelial Cell Monolayer.

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Hu, Mi; Chang, Hao; Zhang, He; Wang, Jing; Lei, Wen-Xi; Li, Bo-Chao; Ren, Ke-Feng; Ji, Jian

2017-07-01

Extracellular matrix and cells are inherent in coordinating and adapting to each other during all physiological and pathological processes. Synthetic materials, however, show rarely reciprocal and spatiotemporal responses to cells, and lacking self-adapting properties as well. Here, a mechanical adaptability based on the matrix metalloproteinase (MMPs) sensitive polyelectrolyte film is reported. Poly-lysine (PLL) and methacrylated hyaluronic acid (HA-MA) nanolayers are employed to build the thin film through the layer-by-layer assembly, and it is further crosslinked using MMP sensitive peptides, which endows the films with changeable mechanical properties in response to MMPs. It is demonstrated that stiffness of the (PLL/HA-MA) films increases with the crosslinking, and then decreases in response to a treatment of enzyme. Consequently, the crosslinked (PLL/HA-MA) films reveal effective growth of endothelial cells (ECs), leading to fast formation of EC monolayer. Importantly, significantly improved endothelial function of the EC monolayer, which is characterized by integrity, biomolecules release, expression of function related gene, and antithrombotic properties, is achieved along with the decrosslinking of the film because of EC-secreted MMPs. These results suggest that mechanical adaptability of substrate in Young's modulus plays a significant role in endothelial progression, which shows great application potential in tissue engineering, regenerative medicine, and organ-on-a-chip. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Visualization of coronary venous anatomy by cardiovascular magnetic resonance

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Crean Andrew

2009-08-01

Full Text Available Abstract Background Coronary venous imaging with whole-heart cardiovascular magnetic resonance (CMR angiography has recently been described using developmental pulse sequences and intravascular contrast agents. However, the practical utility of coronary venous imaging will be for patients with heart failure in whom cardiac resynchronisation therapy (CRT is being considered. As such complementary information on ventricular function and myocardial viability will be required. The aim of this study was to determine if the coronary venous anatomy could be depicted as part of a comprehensive CMR protocol and using a standard extracellular contrast agent. Methods and Results Thirty-one 3D whole heart CMR studies, performed after intravenous administration of 0.05 mmol/kg gadolinium DTPA, were reviewed. The cardiac venous system was visualized in all patients. The lateral vein of the left ventricle was present in 74%, the anterior interventricular vein in 65%, and the posterior interventricular vein in 74% of patients. The mean maximum distance of demonstrable cardiac vein on the 3D images was 81.5 mm and was dependent on the quality of the 3D data set. Five patients showed evidence of myocardial infarction on late gadolinium enhancement (LGE images. Conclusion Coronary venous anatomy can be reliably demonstrated using a comprehensive CMR protocol and a standard extracellular contrast agent. The combination of coronary venous imaging, assessment of ventricular function and LGE may be useful in the management of patients with LV dysfunction being considered for CRT.

The endothelial border to health

DEFF Research Database (Denmark)

Hansen, Nina Wærling; Hansen, Anker Jon; Sams, Anette

2017-01-01

player for maintenance of health and for development of a number of diseases. Endothelial dysfunction is known to be an important component of type 2 diabetes, but is also assumed to be involved in many other diseases, for example, rheumatoid arthritis, inflammatory bowel disease, asthma...... extracellular proteins form epitopes for potential specific antibody formation upon interactions with reducing sugars. This paper reviews the endothelial metabolism, biology, inflammatory processes, physical barrier functions, and summarizes evidence that although stochastic in nature, endothelial responses...... to hyperglycemia are major contributors to disease pathophysiology. We present molecular and mechanistic evidence that both biological and physical barriers, protein function, specific immunity, and inflammatory processes are compromised by hyperglycemic events and thus, hyperglycemic events alone should...

Congenital portosystemic venous connections and other abdominal venous abnormalities in patients with polysplenia and functionally univentricular heart disease: a case series and literature review.

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McElhinney, Doff B; Marx, Gerald R; Newburger, Jane W

2011-01-01

Published case reports suggest that congenital portosystemic venous connections (PSVC) and other abdominal venous anomalies may be relatively frequent and potentially important in patients with polysplenia syndrome. Our objective was to investigate the frequency and range of portal and other abdominal systemic venous anomalies in patients with polysplenia and inferior vena cava (IVC) interruption who underwent a cavopulmonary anastomosis procedure at our center, and to review the published literature on this topic and the potential clinical importance of such anomalies. Retrospective cohort study and literature review were used. Among 77 patients with heterotaxy, univentricular heart disease, and IVC interruption who underwent a bidirectional Glenn and/or modified Fontan procedure, pulmonary arteriovenous malformations were diagnosed in 33 (43%). Bilateral superior vena cavas were present in 42 patients (55%). Despite inadequate imaging in many patients, a partial PSVC, dual IVCs, and/or renal vein anomalies were detected in 15 patients (19%). A PSVC formed by a tortuous vessel running from the systemic venous system to the extrahepatic portal vein was found in six patients (8%). Abdominal venous anomalies other than PSVC were documented in 13 patients (16%), including nine (12%) with some form of duplicated IVC system, with a large azygous vein continuing to the superior vena cava and a parallel, contralateral IVC of similar or smaller size, and seven with renal vein anomalies. In patients with a partial PSVC or a duplicate IVC that connected to the atrium, the abnormal connection allowed right-to-left shunting. PSVC and other abdominal venous anomalies may be clinically important but under-recognized in patients with IVC interruption and univentricular heart disease. In such patients, preoperative evaluation of the abdominal systemic venous system may be valuable. More data are necessary to determine whether there is a pathophysiologic connection between the

Loss of 51chromium, lactate dehydrogenase, and 111indium as indicators of endothelial cell injury

International Nuclear Information System (INIS)

Chopra, J.; Joist, J.H.; Webster, R.O.

1987-01-01

Injury to endothelial cells appears to be an important initial event in the pathogenesis of many diseases such as acute lung injury, venous and arterial thromboembolism, and atherosclerosis. Different methods for detecting damage to cultured endothelial cells have been described. However, their relative sensitivity as markers of endothelial cell damage has not been adequately determined. We compared the loss of 51 Chromium ( 51 Cr), the cytoplasmic enzyme lactate dehydrogenase (LDH), and 111 Indium ( 111 In) from endothelial cells upon exposure to several injurious agents. Cultured bovine pulmonary artery endothelial cells in confluent monolayers were labeled with 51 Cr or 111 Inoxine and exposed to increasing concentrations of the nonionic detergent, Triton X-100 (0.2 to 1%), hydrogen peroxide (1 to 500 microM), or neutrophils stimulated with phorbol myristate acetate. With all forms of injury, loss of 51 Cr occurred earlier and to a greater extent than LDH loss which in turn was greater than loss of 111 In. Substantial loss of 51 Cr was observed in the absence of appreciable ultrastructural damage to endothelial cell external membranes. The findings may reflect the relative ease with which small molecules such as adenine nucleotides ( 51 Cr-labeled) escape whereas larger molecules such as LDH and proteins binding 111 In are retained intracellularly. Thus, 51 Cr loss appears to be a more sensitive indicator of sublytic endothelial cell injury than either 111 In or LDH release

Protective effects of flavanol-rich dark chocolate on endothelial function and wave reflection during acute hyperglycemia.

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Grassi, Davide; Desideri, Giovambattista; Necozione, Stefano; Ruggieri, Fabrizio; Blumberg, Jeffrey B; Stornello, Michele; Ferri, Claudio

2012-09-01

Nitric oxide plays a pivotal role in regulating vascular tone. Different studies show endothelial function is impaired during hyperglycemia. Dark chocolate increases flow-mediated dilation in healthy and hypertensive subjects with and without glucose intolerance; however, the effect of pretreatment with dark chocolate on endothelial function and other vascular responses to hyperglycemia has not been examined. Therefore, we aimed to investigate the effects of flavanol-rich dark chocolate administration on (1) flow-mediated dilation and wave reflections; (2) blood pressure, endothelin-1 and oxidative stress, before and after oral glucose tolerance test (OGTT). Twelve healthy volunteers (5 males, 28.2±2.7 years) randomly received either 100 g/d dark chocolate or flavanol-free white chocolate for 3 days. After 7 days washout period, volunteers were switched to the other treatment. Flow-mediated dilation, stiffness index, reflection index, peak-to-peak time, blood pressure, endothelin-1 and 8-iso-PGF(2α) were evaluated after each treatment phase and OGTT. Compared with white chocolate, dark chocolate ingestion improved flow-mediated dilation (P=0.03), wave reflections, endothelin-1 and 8-iso-PGF(2α) (Pwave reflections, blood pressure, and endothelin-1 and 8-iso-PGF(2α) increased after OGTT. OGTT causes acute, transient impairment of endothelial function and oxidative stress, which is attenuated by flavanol-rich dark chocolate. These results suggest cocoa flavanols may contribute to vascular health by reducing the postprandial impairment of arterial function associated with the pathogenesis of atherosclerosis.

Curcumin supplementation improves vascular endothelial function in healthy middle-aged and older adults by increasing nitric oxide bioavailability and reducing oxidative stress.

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Santos-Parker, Jessica R; Strahler, Talia R; Bassett, Candace J; Bispham, Nina Z; Chonchol, Michel B; Seals, Douglas R

2017-01-03

We hypothesized that curcumin would improve resistance and conduit artery endothelial function and large elastic artery stiffness in healthy middle-aged and older adults. Thirty-nine healthy men and postmenopausal women (45-74 yrs) were randomized to 12 weeks of curcumin (2000 mg/day Longvida®; n=20) or placebo (n=19) supplementation. Forearm blood flow response to acetylcholine infusions (FBF ACh ; resistance artery endothelial function) increased 37% following curcumin supplementation (107±13 vs. 84±11 AUC at baseline, P=0.03), but not placebo (P=0.2). Curcumin treatment augmented the acute reduction in FBF ACh induced by the nitric oxide synthase inhibitor NG monomethyl-L-arginine (L-NMMA; P=0.03), and reduced the acute increase in FBF ACh to the antioxidant vitamin C (P=0.02), whereas placebo had no effect (both P>0.6). Similarly, brachial artery flow-mediated dilation (conduit artery endothelial function) increased 36% in the curcumin group (5.7±0.4 vs. 4.4±0.4% at baseline, P=0.001), with no change in placebo (P=0.1). Neither curcumin nor placebo influenced large elastic artery stiffness (aortic pulse wave velocity or carotid artery compliance) or circulating biomarkers of oxidative stress and inflammation (all P>0.1). In healthy middle-aged and older adults, 12 weeks of curcumin supplementation improves resistance artery endothelial function by increasing vascular nitric oxide bioavailability and reducing oxidative stress, while also improving conduit artery endothelial function.

Transient impedance changes in venous endothelial monolayers as a biological radiation dosimetry response

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Erik Fossum Young

2012-10-01

Full Text Available In March of 2011, a magnitude 9.0 earthquake and subsequent 14 m-high tsunami caused major damage to the Fukushima Daiichi nuclear power plant in Japan.  While cancer incidence in the radiation-exposed population is a logical concern, the complex effects of radiation on the heart and cardiovascular system are also of interest.  Immediate and early vascular radiation effects could be exploited as a dosimetry modality.  To test whether non-coronary vasculature exhibited transient perturbation in barrier function, video microscopy studies and Electric Cell Substrate Impedance Sensing technology were used to probe very subtle changes in primary human vascular endothelium.  Human umbilical vein endothelial cell (HUVEC monolayers exhibit a transient, statistically significant decrease (P = 0.017 in monolayer resistance 3 h after irradiation with 5.0 Gy of g rays.  Radiation induced perturbations in HUVEC monolayer permeability are similar in magnitude and kinetics to those observed in coronary arterial endothelium.  Therefore, at least two types of vasculature respond to radiation on ECIS arrays with an early transient disruption in permeability.  The finding supports the use of early passage HUVECs for use in bioelectric dosimetry studies of vasculature and suggests that permeability of vessels could potentially serve as a biological dosimetry tool.

Endothelial dysfunction and functional status of intestinal mucosal barrier in asphyxiated low birth weight infants

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Huseynova S.A.

2016-03-01

Full Text Available Aim of study. The main prpose of present study was to determine the effect of endothelial dysfunction to the levels of markers of functional state of digestive system in infants with perinatal hypoxia. Materials and methods. The neuronal dysfunction was detected basing on the levels of NSE and NR2 antibodies. The functional state of gastrointestinal tract was estimated by IFABP, sLFABP, MUC-2, ITF, LBP. As the markers of endothelial dysfunction it was detected endotelin-1 and NO. The concentrations of markers were determined in peripheral blood of 66 preterm newborns exposure intrauterine hypoxia with 32–36 weeks of gestational age, which were classified as asphyxiated (1st group, n=30, non asphyxiated (2nd group, n=36 infants. Control group consisted of 22 healthy preterm babies. Results. It was not detected significant difference of NSE and NR2 antibodies levels between 1st and 2nd groups. The endothelin-1 concentrations significantly decreased in asphyxiated group in the background of high NO levels. The elevated level of IFABP in asphyxiated infants associated with compensative increasing of ITF and low anti endotoxine immunity. Conclusion. Endothelial dysfunction is one of the main factor resulting in hypoxic-ischemic injury of gastrointestinal tract in asphyxiated low birth weight infants.

ENDOVASCULAR TREATMENT FOR DISORDERS OF THE VENOUS SYSTEM

Directory of Open Access Journals (Sweden)

A. G. Osiev

2015-01-01

Full Text Available The annual rate of deep vein thrombosis in general population is from 5 to 9 cases per 10 000, whereas for venous thromboembolism (deep vein thrombosis and pulmonary embolism taken together amounts to 14 cases per 10 000. To improve longterm results of therapy for thrombosis of deep veins of the lower extremities, it is important to restore venous function and outflow. Anticoagulant therapy with low weight or non-fractionated heparin preparations remains the most widely used method of management. However, total or partial thrombosis resolution under anticoagulant treatment is achieved only in 4 and 14% of cases, respectively. Thrombolysis allows for early resorption of the thrombus by means of a minimally invasive procedure with lower risk of complication. After the venous flow is restored, the aim of treatment is to prevent damage to the venous valves, venous hypertension and repeated thrombosis with development of the post-thrombotic syndrome. Compared to anticoagulation, systemic thrombolysis has the benefit of more rapid clot resorption and less damage to the venous valve. One of its serious limitations is a high bleeding risk related to higher doses of the drug administered through a peripheral vein catheter. Therefore, selective intra-clot administration of thombolytics (direct catheter thrombolysis has been suggested as an alternative. For more effective therapy with the use of lower doses of thrombolytics, the so called pharmaco-mechanical thrombectomy has been developed. Venous stenosis hindering the venous outflow is frequently seen after direct catheter or pharmaco-mechanical thrombolysis. Angioplasty with stent placement is recommended in the cases with residual venous abnormality after successful thrombolysis and thrombectomy. 

Endogenous Vascular Endothelial Growth Factor-A (VEGF-A) Maintains Endothelial Cell Homeostasis by Regulating VEGF Receptor-2 Transcription*

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E, Guangqi; Cao, Ying; Bhattacharya, Santanu; Dutta, Shamit; Wang, Enfeng; Mukhopadhyay, Debabrata

2012-01-01

Vascular endothelial growth factor A (VEGF-A) is one of the most important factors controlling angiogenesis. Although the functions of exogenous VEGF-A have been widely studied, the roles of endogenous VEGF-A remain unclear. Here we focused on the mechanistic functions of endogenous VEGF-A in endothelial cells. We found that it is complexed with VEGF receptor 2 (VEGFR-2) and maintains a basal expression level for VEGFR-2 and its downstream signaling activation. Endogenous VEGF-A also controls expression of key endothelial specific genes including VEGFR-2, Tie-2, and vascular endothelial cadherin. Of importance, endogenous VEGF-A differs from exogenous VEGF-A by regulating VEGFR-2 transcription through mediation of FoxC2 binding to the FOX:ETS motif, and the complex formed by endogenous VEGF-A with VEGFR-2 is localized within the EEA1 (early endosome antigen 1) endosomal compartment. Taken together, our results emphasize the importance of endogenous VEGF-A in endothelial cells by regulating key vascular proteins and maintaining the endothelial homeostasis. PMID:22167188

Iliofemoral and iliocaval interventions in deep venous thrombosis

International Nuclear Information System (INIS)

Haage, P.; Guenther, R.W.

2005-01-01

Significant spontaneous thrombus disintegration in deep venous thrombosis (DVT) occurs very infrequently. On the contrary, these thrombi are prone to appositional growth and migration into the pulmonary arteries. The development of chronic venous insufficiency due to post-thrombotic syndrome is a frequent consequence of DVT. Therapeutic options in DVT include anticoagulation and recanalising procedures such as thrombolysis and thrombectomy. After appropriate indication assessment, the interventional radiologist can offer an efficacy-proven minimally-invasive vessel restitution approach by performing locoregional thrombolysis, pharmacomechanical therapy or, particularly in iliocaval thrombosis, mechanical thrombectomy. These methods not only serve to restitute of vessel patency, but also allow preserving venous valve function. In DVT with recurrent pulmonary embolism, retrievable filters with extended implantation duration can be deployed. In chronic proximal venous flow obstruction or in case of significant residual stenosis after thrombolysis, balloon angioplasty with stent implantation is the treatment modality of choice. Consequently, the radiologist can adopt an important role in the treatment of extensive venous disease. In this article, the treatment modalities concerning iliofemoral and iliocaval thrombosis are demonstrated and illustrated. (orig.)

Omega-3 Fatty Acid Supplementation Improves Endothelial Function in Primary Antiphospholipid Syndrome: A Small-Scale Randomized Double-Blind Placebo-Controlled Trial.

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Felau, Sheylla M; Sales, Lucas P; Solis, Marina Y; Hayashi, Ana Paula; Roschel, Hamilton; Sá-Pinto, Ana Lúcia; Andrade, Danieli Castro Oliveira De; Katayama, Keyla Y; Irigoyen, Maria Claudia; Consolim-Colombo, Fernanda; Bonfa, Eloisa; Gualano, Bruno; Benatti, Fabiana B

2018-01-01

Endothelial cells are thought to play a central role in the pathogenesis of antiphospholipid syndrome (APS). Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation has been shown to improve endothelial function in a number of diseases; thus, it could be of high clinical relevance in APS. The aim of this study was to evaluate the efficacy of n-3 PUFA supplementation on endothelial function (primary outcome) of patients with primary APS (PAPS). A 16-week randomized clinical trial was conducted with 22 adult women with PAPS. Patients were randomly assigned (1:1) to receive placebo (PL, n  = 11) or n-3 PUFA (ω-3, n  = 11) supplementation. Before (pre) and after (post) 16 weeks of the intervention, patients were assessed for endothelial function (peripheral artery tonometry) (primary outcome). Patients were also assessed for systemic markers of endothelial cell activation, inflammatory markers, dietary intake, international normalized ratio (INR), and adverse effects. At post, ω-3 group presented significant increases in endothelial function estimates reactive hyperemia index (RHI) and logarithmic transformation of RHI (LnRHI) when compared with PL (+13 vs. -12%, p  = 0.06, ES = 0.9; and +23 vs. -22%, p  = 0.02, ES = 1.0). No changes were observed for e-selectin, vascular adhesion molecule-1, and fibrinogen levels ( p  > 0.05). In addition, ω-3 group showed decreased circulating levels of interleukin-10 (-4 vs. +45%, p  = 0.04, ES = -0.9) and tumor necrosis factor (-13 vs. +0.3%, p  = 0.04, ES = -0.95) and a tendency toward a lower intercellular adhesion molecule-1 response (+3 vs. +48%, p  = 0.1, ES = -0.7) at post when compared with PL. No changes in dietary intake, INR, or self-reported adverse effects were observed. In conclusion, 16 weeks of n-3 PUFA supplementation improved endothelial function in patients with well-controlled PAPS. These results support a role of n-3 PUFA supplementation as an

Omega-3 Fatty Acid Supplementation Improves Endothelial Function in Primary Antiphospholipid Syndrome: A Small-Scale Randomized Double-Blind Placebo-Controlled Trial

Science.gov (United States)

Felau, Sheylla M.; Sales, Lucas P.; Solis, Marina Y.; Hayashi, Ana Paula; Roschel, Hamilton; Sá-Pinto, Ana Lúcia; Andrade, Danieli Castro Oliveira De; Katayama, Keyla Y.; Irigoyen, Maria Claudia; Consolim-Colombo, Fernanda; Bonfa, Eloisa; Gualano, Bruno; Benatti, Fabiana B.

2018-01-01

Endothelial cells are thought to play a central role in the pathogenesis of antiphospholipid syndrome (APS). Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation has been shown to improve endothelial function in a number of diseases; thus, it could be of high clinical relevance in APS. The aim of this study was to evaluate the efficacy of n-3 PUFA supplementation on endothelial function (primary outcome) of patients with primary APS (PAPS). A 16-week randomized clinical trial was conducted with 22 adult women with PAPS. Patients were randomly assigned (1:1) to receive placebo (PL, n = 11) or n-3 PUFA (ω-3, n = 11) supplementation. Before (pre) and after (post) 16 weeks of the intervention, patients were assessed for endothelial function (peripheral artery tonometry) (primary outcome). Patients were also assessed for systemic markers of endothelial cell activation, inflammatory markers, dietary intake, international normalized ratio (INR), and adverse effects. At post, ω-3 group presented significant increases in endothelial function estimates reactive hyperemia index (RHI) and logarithmic transformation of RHI (LnRHI) when compared with PL (+13 vs. −12%, p = 0.06, ES = 0.9; and +23 vs. −22%, p = 0.02, ES = 1.0). No changes were observed for e-selectin, vascular adhesion molecule-1, and fibrinogen levels (p > 0.05). In addition, ω-3 group showed decreased circulating levels of interleukin-10 (−4 vs. +45%, p = 0.04, ES = −0.9) and tumor necrosis factor (−13 vs. +0.3%, p = 0.04, ES = −0.95) and a tendency toward a lower intercellular adhesion molecule-1 response (+3 vs. +48%, p = 0.1, ES = −0.7) at post when compared with PL. No changes in dietary intake, INR, or self-reported adverse effects were observed. In conclusion, 16 weeks of n-3 PUFA supplementation improved endothelial function in patients with well-controlled PAPS. These results support a role of n-3 PUFA supplementation as an

The Role of Vitamin D in Blood Pressure, Endothelial and Renal Function in Postmenopausal Women

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Suzanne C. Ho

2013-07-01

Full Text Available Background: Vitamin D is a pro-hormone that plays an essential role in the vasculature and in kidney function. Aims: To review the extra-skeletal effects of vitamin D on blood pressure, endothelial and renal function with emphasis on recent findings in postmenopausal women. Methods: Included in this review was a PubMed database search for English language articles through March 2013. This review discussed the physiology and definition of vitamin D deficiency, the recent evidence for the role vitamin D in blood pressure, vascular and renal function. Results: Experimental and epidemiological data suggest that vitamin D plays an important role in the vasculature and in kidney function. Low vitamin D concentrations appear to significantly associate with hypertension, endothelial and renal dysfunction. However, the results of clinical trials have generally been mixed. Studies specifically conducted among postmenopausal women are limited and findings are still inconsistent. Conclusions: Definitive studies are warranted to elucidate the effects of vitamin D supplementation on vascular and renal function and a more detailed work is needed to outline the route, duration and optimal dose of supplementation. It is premature to recommend vitamin D as a therapeutic option in the improvement of vascular and renal function at the current stage.

Effect of vitamin D on endothelial progenitor cells function.

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Yoav Hammer

Full Text Available Endothelial progenitor cells (EPCs are a population of bone marrow-derived cells, which have an important role in the process of endothelialization and vascular repair following injury. Impairment of EPCs, which occurs in patients with diabetes, was shown to be related to endothelial dysfunction, coronary artery disease (CAD and adverse clinical outcomes. Recent evidence has shown that calcitriol, the active hormone of vitamin D, has a favorable impact on the endothelium and cardiovascular system. There is limited data on the effect of vitamin D on EPCs function.To examine the in vitro effects of Calcitriol on EPCs from healthy subjects and patients with diabetes.Fifty-one patients with type 2 diabetes (60±11 years, 40% women, HbA1C: 9.1±0.8% and 23 healthy volunteers were recruited. EPCs were isolated and cultured with and without calcitriol. The capacity of the cells to form colony-forming units (CFUs, their viability (measured by MTT assay, KLF-10 levels and angiogenic markers were evaluated after 1 week of culture.In diabetic patients, EPC CFUs and cell viability were higher in EPCs exposed to calcitriol vs. EPCs not exposed to calcitriol [EPC CFUs: 1.25 (IQR 1.0-2.0 vs. 0.5 (IQR 0.5-1.9, p < 0.001; MTT:0.62 (IQR 0.44-0.93 vs. 0.52 (IQR 0.31-0.62, p = 0.001]. KLF-10 levels tended to be higher in EPCs exposed to vitamin D, with no differences in angiopoietic markers. In healthy subjects, calcitriol supplementation also resulted in higher cell viability [MTT: 0.23 (IQR 0.11-0.46 vs. 0.19 (0.09-0.39, p = 0.04], but without differences in CFU count or angiopoietic markers.In patients with diabetes mellitus, in vitro vitamin D supplementation improved EPCs capacity to form colonies and viability. Further studies regarding the mechanisms by which vitamin D exerts its effect are required.

Deep venous thrombosis and postthrombotic syndrome: invasive management.

Science.gov (United States)

Comerota, A J

2015-03-01

Invasive management of postthrombotic syndrome encompasses the two ends of the deep vein thrombosis spectrum, patients with acute iliofemoral deep vein thrombosis and those with chronic postthrombotic iliofemoral venous obstruction. Of all patients with acute deep vein thrombosis, those with involvement of the iliofemoral segments have the most severe chronic postthrombotic morbidity. Catheter-based techniques now permit percutaneous treatment to eliminate thrombus, restore patency, potentially maintain valvular function, and improve quality of life. Randomized trial data support an initial treatment strategy of thrombus removal. Failure to eliminate acute thrombus from the iliofemoral system leads to chronic postthrombotic obstruction of venous outflow. Debilitating chronic postthrombotic symptoms of the long-standing obstruction of venous outflow can be reduced by restoring unobstructed venous drainage from the profunda femoris vein to the vena cava. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

The impact of decreases in air temperature and increases in ozone on markers of endothelial function in individuals having type-2 diabetes

Science.gov (United States)

Several studies have reported an association between air pollution and endothelial dysfunction, especially in individuals having diabetes. However, very few studies have examined the impact of air temperature on endothelial function. The objective of this analysis was to investig...

Amiloride Improves Endothelial Function and Reduces Vascular Stiffness in Female Mice Fed a Western Diet

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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.

Flavonoid-Rich Apple Improves Endothelial Function in Individuals at Risk for Cardiovascular Disease: A Randomized Controlled Clinical Trial.

Science.gov (United States)

Bondonno, Nicola P; Bondonno, Catherine P; Blekkenhorst, Lauren C; Considine, Michael J; Maghzal, Ghassan; Stocker, Roland; Woodman, Richard J; Ward, Natalie C; Hodgson, Jonathan M; Croft, Kevin D

2018-02-01

The cardioprotective effects of apples are primarily attributed to flavonoids, found predominantly in the skin. This study aimed to determine if acute and/or chronic (4 weeks) ingestion of flavonoid-rich apples improves endothelial function, blood pressure (BP), and arterial stiffness in individuals at risk for cardiovascular diseases (CVD). In this randomized, controlled cross-over trial, acute and 4 week intake of apple with skin (high flavonoid apple, HFA) is compared to intake of apple flesh only (low flavonoid apple, LFA) in 30 participants. The primary outcome is endothelial function assessed using flow-mediated dilation (FMD) of the brachial artery, while main secondary outcomes are 24 h ambulatory BP and arterial stiffness. Other outcomes include fasting serum glucose and lipoprotein profile, plasma heme oxygenase-1 (Hmox-1), F 2 -isoprostanes, flavonoid metabolites, and plasma and salivary nitrate (NO 3 - ) and nitrite (NO 2 - ) concentrations. Compared to LFA control, the HFA results in a significant increase in FMD acutely (0.8%, p flavonoid metabolites (p effect of apple skin on endothelial function, both acutely and chronically. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Normal endothelial function in patients with mild-to-moderate psoriasis: a case-control study

DEFF Research Database (Denmark)

Jensen, Peter R; Zachariae, Claus; Hansen, Peter

2011-01-01

-dependent and technically demanding ultrasound measurement of brachial artery flow-mediated vasodilation. Therefore, we decided to measure endothelial function and other cardiovascular risk factors in patients with mild-to-moderate psoriasis (n = 30) and controls (n = 30) using a newer and relatively operator......Evidence is increasing that severe psoriasis is an independent cardiovascular risk factor. Results from case-control studies of endothelial dysfunction, a marker of early atherosclerosis, in patients with moderate-to-severe psoriasis have been conflicting and were conducted with operator...... blood pressures, and plasma levels of triglycerides, very-low-density lipoprotein cholesterol and glycated glucose, compared with controls. This indicates that even mild-to-moderate psoriasis may be regarded as a systemic inflammatory disease, and that an increased risk of cardiovascular morbidity may...

Endothelial dysfunction – A predictor of atherosclerosis | Chhabra ...

African Journals Online (AJOL)

Endothelial dysfunction is a systemic disorder and a critical element in the pathogenesis of atherosclerotic diseases and its complications. Growing evidences suggest that the individual burden of currently known cardiovascular risk factors is not the only determinant of endothelial function; rather endothelial integrity ...

Influence of methylenetetrahydrofolate reductase genotype, exercise and other risk factors on endothelial function in healthy individuals.

Science.gov (United States)

Pullin, Catherine H; Wilson, John F; Ashfield-Watt, Pauline A L; Clark, Zoë E; Whiting, Jenny M; Lewis, Malcolm J; McDowell, Ian F W

2002-01-01

Cardiovascular disease has a multifactorial aetiology that is influenced by both genetic and environmental factors. Endothelial dysfunction is a key event in the pathogenesis of vascular disease that occurs before structural vascular changes or clinical symptoms are evident. Conventional risk factors, for example hypertension and diabetes mellitus, are associated with endothelial dysfunction, but the influence of other putative risk factors is not clear. The methylenetetrahydrofolate reductase (MTHFR) C677T genotype, a common polymorphism that induces hyperhomocysteinaemia, has been proposed as being a genetic risk factor for cardiovascular disease. A total of 126 healthy adults recruited by MTHFR C677T genotype (42 of each genotype, i.e. CC, CT and TT) underwent assessment of endothelial function. Brachial artery endothelium-dependent flow-mediated dilatation (FMD) was measured using high-resolution ultrasonic vessel "wall-tracking". Using multiple regression analysis, MTHFR genotype and 21 other subject and subject-lifestyle variables were investigated as potential predictors of endothelial function. FMD was influenced positively by frequency of aerobic exercise and by hormone replacement therapy, and negatively by increases in systolic blood pressure. MTHFR C677T genotype and the associated variation in plasma homocysteine levels did not influence FMD. Additionally, other factors, including plasma cholesterol and self-supplementation with either antioxidant vitamins or cod liver oil, showed no significant relationship with FMD, although these findings are compromised by the narrow range studied for cholesterol and the small number of subjects taking supplements. These observations have implications for risk factor management in the primary prevention of cardiovascular disease in healthy individuals.

Hepatectomy simulation discrepancy between radionuclide receptor imaging and CT volumetry. Influence of decreased unilateral portal venous flow

International Nuclear Information System (INIS)

Akaki, Shiro; Okumura, Yoshihiro; Sasai, Nobuya; Sato, Shuhei; Tsunoda, Masatoshi; Kuroda, Masahiro; Kanazawa, Susumu; Hiraki, Yoshio

2003-01-01

Regional dysfunction demonstrated by Tc-99m-diethylenetriamine-penta-acetic acid-galactosyl human serum albumin (GSA) scintigraphy due to regional decrease in the portal venous flow has previously been reported. In this study, we call attention to the significance of unilateral portal venous flow decrease for preoperative hepatectomy simulation, and evaluate the hepatectomy simulation discrepancy between Tc-99m-GSA single-photon emission computed tomography (SPECT) and CT volumetry. Twenty-four hepatectomy candidates underwent preoperative hepatectomy simulation by both Tc-99m-GSA SPECT and CT volumetry. Both anatomical and functional resection ratios were calculated by means of CT volumetry and Tc-99m-GSA SPECT, respectively. The differences and ratios between anatomical and functional resection ratios were calculated in all patients, and compared in patients with and without unilateral portal venous flow decrease. Anatomical resection ratios were 28.0±11.7 (mean±standard deviation) in patients with unilateral portal venous flow decrease, and 42.1±15.7 in patients without unilateral portal venous flow decrease (p=0.0127). Functional resection ratios were 14.7±12.8 in patients with unilateral portal venous flow decrease and 40.5±14.6 in patients without (p=0.0004). The differences between anatomical and functional resection ratios were 13.0±7.9 in patients with unilateral portal venous flow decrease and 5.6±3.1 in patients without (p=0.0099). The ratios between anatomical and functional resection ratios were 0.48±0.29 in patients with unilateral portal venous flow decrease and 0.86±0.10 in patients without (p=0.0018). In 12 of the 13 patients with unilateral portal venous flow decrease, anatomical resection ratios were found to be larger than functional resection ratios, whereas this happened in only 6 of 11 patients without unilateral portal venous flow decrease (p=0.0063). Unilateral portal venous flow decrease is suspected to be a major factor in the

Venous Ulcers

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Caprini, J.A.; Partsch, H.; Simman, R.

2013-01-01

Venous leg ulcers are the most frequent form of wounds seen in patients. This article presents an overview on some practical aspects concerning diagnosis, differential diagnosis and treatment. Duplex ultrasound investigations are essential to ascertain the diagnosis of the underlying venous pathology and to treat venous refluxes. Differential diagnosis includes mainly other vascular lesions (arterial, microcirculatory causes), hematologic and metabolic diseases, trauma, infection, malignancies. Patients with superficial venous incompetence may benefit from endovenous or surgical reflux abolition diagnosed by Duplex ultrasound. The most important basic component of the management is compression therapy, for which we prefer materials with low elasticity applied with high initial pressure (short-stretch bandages and Velcro-strap devices). Local treatment should be simple, absorbing and not sticky dressings keeping adequate moisture balance after debridement of necrotic tissue and biofilms are preferred. After the ulcer is healed compression therapy should be continued in order to prevent recurrence. PMID:26236636

Endothelial MMP14 is required for endothelial-dependent growth support of human airway basal cells

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Ding, Bi-Sen; Gomi, Kazunori; Rafii, Shahin; Crystal, Ronald G.; Walters, Matthew S.

2015-01-01

ABSTRACT Human airway basal cells are the stem (or progenitor) population of the airway epithelium, and play a central role in anchoring the epithelium to the basement membrane. The anatomic position of basal cells allows for potential paracrine signaling between them and the underlying non-epithelial stromal cells. In support of this, we have previously demonstrated that endothelial cells support growth of basal cells during co-culture through vascular endothelial growth factor A (VEGFA)-mediated signaling. Building on these findings, we found, by RNA sequencing analysis, that basal cells expressed multiple fibroblast growth factor (FGF) ligands (FGF2, FGF5, FGF11 and FGF13) and that only FGF2 and FGF5 were capable of functioning in a paracrine manner to activate classical FGF receptor (FGFR) signaling. Antibody-mediated blocking of FGFR1 during basal-cell–endothelial-cell co-culture significantly reduced the endothelial-cell-dependent basal cell growth. Stimulation of endothelial cells with basal-cell-derived growth factors induced endothelial cell expression of matrix metallopeptidase 14 (MMP14), and short hairpin RNA (shRNA)-mediated knockdown of endothelial cell MMP14 significantly reduced the endothelial-cell-dependent growth of basal cells. Overall, these data characterize a new growth-factor-mediated reciprocal ‘crosstalk’ between human airway basal cells and endothelial cells that regulates proliferation of basal cells. PMID:26116571

Association between anthropometry, cardiometabolic risk factors, & early life factors & adult measures of endothelial function: Results from the New Delhi Birth Cohort

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Mark D Huffman

2015-01-01

Full Text Available Background & objectives: Abnormal endothelial function represents a preclinical marker of atherosclerosis. This study was conducted to evaluate associations between anthropometry, cardiometabolic risk factors, and early life factors and adult measures of endothelial function in a young urban Indian cohort free of clinical cardiovascular disease. Methods: Absolute changes in brachial artery diameter following cuff inflation and sublingual nitroglycerin (400 µg were recorded to evaluate endothelium-dependent and -independent measures of endothelial function in 600 participants (362 men; 238 women from the New Delhi Birth Cohort (2006-2009. Data on anthropometry, cardiometabolic risk factors, medical history, socio-economic position, and lifestyle habits were collected. Height and weight were recorded at birth, two and 11 yr of age. Age- and sex-adjusted linear regression models were developed to evaluate these associations. Results: The mean age of participants was 36±1 yr. Twenty two per cent men and 29 per cent women were obese (BMI th > 30 kg/m [2] . Mean systolic blood pressure (SBP was 131±14 and 119±13 mmHg, and diabetes prevalence was 12 and 8 per cent for men and women, respectively. Brachial artery diameter was higher for men compared with women both before (3.48±0.37 and 2.95±0.35 cm and after hyperaemia (3.87±0.37 vs. 3.37±0.35 cm. A similar difference was seen before and after nitroglycerin. Markers of increased adiposity, smoking, SBP, and metabolic syndrome, but not early life anthropometry, were inversely associated with endothelial function after adjustment for age and sex. Interpretation & conclusions: The analysis of the current prospective data from a young urban Indian cohort showed that cardiometabolic risk factors, but not early life anthropometry, were associated with worse endothelial function.

Curcumin supplementation improves vascular endothelial function in healthy middle-aged and older adults by increasing nitric oxide bioavailability and reducing oxidative stress

OpenAIRE

Santos-Parker, Jessica R.; Strahler, Talia R.; Bassett, Candace J.; Bispham, Nina Z.; Chonchol, Michel B.; Seals, Douglas R.

2017-01-01

We hypothesized that curcumin would improve resistance and conduit artery endothelial function and large elastic artery stiffness in healthy middle-aged and older adults. Thirty-nine healthy men and postmenopausal women (45-74 yrs) were randomized to 12 weeks of curcumin (2000 mg/day Longvida?; n=20) or placebo (n=19) supplementation. Forearm blood flow response to acetylcholine infusions (FBFACh; resistance artery endothelial function) increased 37% following curcumin supplementation (107?13...

The effect of bioresorbable vascular scaffold implantation on distal coronary endothelial function in dyslipidemic swine with and without diabetes.

Science.gov (United States)

van den Heuvel, Mieke; Sorop, Oana; van Ditzhuijzen, Nienke S; de Vries, René; van Duin, Richard W B; Peters, Ilona; van Loon, Janine E; de Maat, Moniek P; van Beusekom, Heleen M; van der Giessen, Wim J; Jan Danser, A H; Duncker, Dirk J

2018-02-01

We studied the effect of bioresorbable vascular scaffold (BVS) implantation on distal coronary endothelial function, in swine on a high fat diet without (HFD) or with diabetes (DM+HFD). Five DM+HFD and five HFD swine underwent BVS implantation on top of coronary plaques, and were studied six months later. Conduit artery segments >5mm proximal and distal to the scaffold and corresponding segments of non-scaffolded coronary arteries, and segments of small arteries within the flow-territory of scaffolded and non-scaffolded arteries were harvested for in vitro vasoreactivity studies. Conduit segments proximal and distal of the BVS edges showed reduced endothelium-dependent vasodilation as compared to control vessels (p≤0.01), with distal segments being most prominently affected(p≤0.01). Endothelial dysfunction was only observed in DM±HFD swine and was principally due to a loss of NO. Endothelium-independent vasodilation and vasoconstriction were unaffected. Surprisingly, segments from the microcirculation distal to the BVS showed enhanced endothelium-dependent vasodilation (pswine, and did not appear to be either NO- or EDHF-mediated. Six months of BVS implantation in DM+HFD swine causes NO-mediated endothelial dysfunction in nearby coronary segments, which is accompanied by a, possibly compensatory, increase in endothelial function of the distal microcirculation. Endothelial dysfunction extending into coronary conduit segments beyond the implantation-site, is in agreement with recent reports expressing concern for late scaffold thrombosis and of early BVS failure in diabetic patients. Copyright © 2017. Published by Elsevier B.V.

Impaired microvascular reactivity and endothelial function in patients with Cushing's syndrome: Influence of arterial hypertension

Czech Academy of Sciences Publication Activity Database

Prázný, M.; Ježková, J.; Horová, E.; Lazárová, V.; Hána, V.; Kvasnička, J.; Pecen, Ladislav; Marek, J.; Škrha, J.; Kršek, M.

2008-01-01

Roč. 57, č. 1 (2008), s. 13-22 ISSN 0862-8408 Institutional research plan: CEZ:AV0Z10300504 Keywords : Cushing’s syndrome * vascular reactivity * endothelial function * oxidative stress * laser Doppler flowmetry Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 1.653, year: 2008

Effects of breed, gender, exercise and white-coat effect on markers of endothelial function in dogs

DEFF Research Database (Denmark)

Moesgaard, Sophia Gry; Holte, A.V.; Mogensen, T.

2007-01-01

This study examines how systemic biomarkers of endothelial function and nitric oxide metabolism are affected by exercise in dogs. Furthermore, breed variation and white-coat effect have been tested by sampling three different dog breeds both in their home and in a clinical setting. Short......-term exercise increased plasma nitrate and nitrite (NOx) and von Willebrand factor (vWf). There was significant difference between Pointers and the small dog breeds Cairn Terriers and Cavalier King Charles Spaniels in the general plasma levels of vWf and asymmetric dimethylarginine (ADMA9. NOx and vWf were...... significantly higher when the sample was taken in the laboratory cf. at home, whereas ADMA and L-arginine were significantly lower. In conclusion, both short-term exercise and white-coat effect influence several plasma markers of endothelial function depending also on the breed and gender of the dogs...

Effects of benazepril on functional activity of endothelial progenitor cells from hypertension patients.

Science.gov (United States)

Li, Yongdong; Alatan, Gaole; Ge, Zhiping; Liu, Dan

2014-01-01

The effect of angiotensin-converting enzyme inhibitors on hypertension patients regarding endothelial progenitor cell (EPC) functions is poorly understood. The aim of this study was to investigate the effects of benazepril on the proliferation, adhesion and migration capacity of EPCs and its possible mechanism. The functions of EPCs from hypertension patients were obviously reduced compared with control group, and this could be improved by benazepril in a dose-dependent manner, whereas this improvement were obviously blocked when AMD3100 were used together. Therefore, benazepril could obviously improve functions of EPCs from hypertension patients, and the potential mechanism may be related to SDF-1/CXCR4 axis.

Fiber-rich diet with brown rice improves endothelial function in type 2 diabetes mellitus: A randomized controlled trial.

Science.gov (United States)

Kondo, Keiko; Morino, Katsutaro; Nishio, Yoshihiko; Ishikado, Atsushi; Arima, Hisatomi; Nakao, Keiko; Nakagawa, Fumiyuki; Nikami, Fumio; Sekine, Osamu; Nemoto, Ken-Ichi; Suwa, Makoto; Matsumoto, Motonobu; Miura, Katsuyuki; Makino, Taketoshi; Ugi, Satoshi; Maegawa, Hiroshi

2017-01-01

A fiber-rich diet has a cardioprotective effect, but the mechanism for this remains unclear. We hypothesized that a fiber-rich diet with brown rice improves endothelial function in patients with type 2 diabetes mellitus. Twenty-eight patients with type 2 diabetes mellitus at a single general hospital in Japan were randomly assigned to a brown rice (n = 14) or white rice (n = 14) diet and were followed for 8 weeks. The primary outcome was changes in endothelial function determined from flow debt repayment by reactive hyperemia using strain-gauge plethysmography in the fasting state. Secondary outcomes were changes in HbA1c, postprandial glucose excursions, and markers of oxidative stress and inflammation. The area under the curve for glucose after ingesting 250 kcal of assigned rice was compared between baseline (T0) and at the end of the intervention (T1) to estimate glucose excursions in each group. Improvement in endothelial function, assessed by fasting flow debt repayment (20.4% vs. -5.8%, p = 0.004), was significantly greater in the brown rice diet group than the white rice diet group, although the between-group difference in change of fiber intake was small (5.6 g/day vs. -1.2 g/day, pdiet group compared with the white rice diet group (0.01 μg/L vs. -0.04 μg/L, p = 0.063). The area under the curve for glucose was subtly but consistently lower in the brown rice diet group (T0: 21.4 mmol/L*h vs. 24.0 mmol/L*h, p = 0.043, T1: 20.4 mmol/L*h vs. 23.3 mmol/L*h, p = 0.046) without changes in HbA1c. Intervention with a fiber-rich diet with brown rice effectively improved endothelial function, without changes in HbA1c levels, possibly through reducing glucose excursions.

Coronary and peripheral endothelial function in HIV patients studied with positron emission tomography and flow-mediated dilation: relation to hypercholesterolemia

DEFF Research Database (Denmark)

Lebech, Anne-Mette; Kristoffersen, Ulrik Sloth; Wiinberg, Niels

2008-01-01

BACKGROUND: The mechanisms underlying increased cardiovascular risk in HIV patients in antiretroviral therapy (ART) are not known. Our aim was to study the endothelial function of the coronary arteries by cardiac perfusion positron emission tomography (PET), in HIV patients with normal or high...... in hypercholesterolemic patients. Also, the increased level of plasma endothelial markers found in HIV patients was not related to hypercholesterolemia....

Haemostatic function and biomarkers of endothelial damage before and after platelet transfusion in patients with acute myeloid leukaemia

DEFF Research Database (Denmark)

Larsen, A M; Leinøe, E B; Johansson, P I

2015-01-01

and after platelet transfusion in patients with acute myeloid leukaemia. MATERIALS AND METHODS: Blood was sampled before, 1 and 24 h after platelet transfusion. Primary and secondary haemostasis was evaluated by whole blood aggregometry (Multiplate) and thromboelastography (TEG). Endothelial biomarkers (s......OBJECTIVES: The beneficial effect of platelet transfusion on haemostasis is well established, but there is emerging evidence that platelet transfusion induces an inflammatory response in vascular endothelial cells. BACKGROUND: We investigated haemostatic function and endothelial biomarkers before......ICAM-1, syndecan-1, sThrombomodulin, sVE-Cadherin) and platelet activation biomarkers (sCD40L, TGF-beta) were investigated along with haematology/biochemistry analyses. RESULTS: Twenty-two patients were included. Despite continued low platelet counts, platelet transfusion normalised the median values...

Effect of Intermittent Energy Restriction on Flow Mediated Dilatation, a Measure of Endothelial Function: A Short Report.

Science.gov (United States)

Headland, Michelle L; Clifton, Peter M; Keogh, Jennifer B

2018-06-04

Intermittent energy restriction is a popular alternative to daily energy restriction for weight loss; however, it is unknown if endothelial function, a risk factor for cardiovascular disease, is altered by periods of severe energy restriction. The objective of the study was to determine the impact of two consecutive very low energy intake days, which is the core component of the 5:2 intermittent energy restriction diet strategy, on endothelial function compared to consecutive ad libitum eating days. The secondary objective was to explore the effects of these dietary conditions on fasting glucose concentrations. This was a 4-week randomized, single-blinded, crossover study of 35 participants. Participants consumed a very low energy diet (500 calories for women, 600 calories for men) on two consecutive days per week and 5 days of habitual eating. In weeks 3 and 4 of the trial, participants had measurements of flow mediated dilatation (FMD) and blood samples taken following either 2 habitual eating days or 2 energy restricted days in a randomized order. FMD values were not different after the two eating states (8.6% vs. 8.3%, p = 0.7). All other outcome variables were unchanged. Endothelial function, as measured by flow mediated dilatation, was not altered by two consecutive very low energy intake days. Further investigations assessing the impact in specific population groups as well as different testing conditions would be beneficial.

The impact of physical activity on endothelial function in middle-aged and elderly subjects: the Ikaria study.

Science.gov (United States)

Siasos, Gerasimos; Chrysohoou, Christina; Tousoulis, Dimitris; Oikonomou, Evangelos; Panagiotakos, Demosthenes; Zaromitidou, Marina; Zisimos, Konstantinos; Marinos, Georgios; Mazaris, Savvas; Kampaksis, Manolis; Papavassiliou, Athanasios G; Pitsavos, Christos; Stefanadis, Christodoulos

2013-01-01

Exercise training and physical activity (PA) have substantial vascular and cardiac health benefits. Ikaria Island has been recognised as having one of the highest longevity rates worldwide and a high percentage of healthy ageing. We examined the relationship between endothelial function and levels of habitual PA to evaluate the factors related to healthy ageing in this population. The study was conducted on a subgroup population of the IKARIA study consisting of 185 middle-aged (40-65 years) and 142 elderly subjects (66-91 years). Endothelial function was evaluated by ultrasound measurement of flow-mediated dilatation (FMD). PA was evaluated using the shortened version of the self-reported International Physical Activity Questionnaire (IPAQ). Subjects in the low PA group (physically inactive and the rest as active. In the overall study population FMD was inversely associated with age (r=-0.24, pphysically active had higher FMD compared with the physically inactive. Physically active subjects in the middle-aged group showed higher FMD compared with the physically active elderly (p=0.008). However, there was no difference in FMD values between middle-aged inactive subjects and the elderly physically active (p=NS). The present study revealed that increased PA was associated with improved endothelial function in middle-aged subjects and that PA in elderly subjects can ameliorate the devastating effects of ageing on arterial wall properties.

Assessment of endothelial function and myocardial flow reserve using {sup 15}O-water PET without attenuation correction

Energy Technology Data Exchange (ETDEWEB)

Tuffier, Stephane; Joubert, Michael; Bailliez, Alban [EA 4650, Normandie Universite, Caen (France); Legallois, Damien [EA 4650, Normandie Universite, Caen (France); Caen University Hospital, Department of Cardiology, Caen (France); Belin, Annette [Caen University Hospital, Department of Cardiac Surgery, Caen (France); Redonnet, Michel [Rouen University Hospital, Department of Cardiac Surgery, Rouen (France); Agostini, Denis [EA 4650, Normandie Universite, Caen (France); Caen University Hospital, Department of Nuclear Medicine, Caen (France); Manrique, Alain [EA 4650, Normandie Universite, Caen (France); Caen University Hospital, Department of Nuclear Medicine, Caen (France); Cyceron PET Centre, Caen (France)

2016-02-15

Myocardial blood flow (MBF) measurement using positron emission tomography (PET) from the washout rate of {sup 15}O-water is theoretically independent of tissue attenuation. The aim of this study was to evaluate the impact of not using attenuation correction in the assessment of coronary endothelial function and myocardial flow reserve (MFR) using {sup 15}O-water PET. We retrospectively processed 70 consecutive {sup 15}O-water PET examinations obtained at rest and during cold pressor testing (CPT) in patients with dilated cardiomyopathy (n = 58), or at rest and during adenosine infusion in heart transplant recipients (n = 12). Data were reconstructed with attenuation correction (AC) and without attenuation correction (NAC) using filtered backprojection, and MBF was quantified using a single compartmental model. The agreement between AC and NAC data was assessed using Lin's concordance correlation coefficient followed by Bland-Altman plot analysis. Regarding endothelial function, NAC PET showed poor reproducibility and poor agreement with AC PET data. Conversely, NAC PET demonstrated high reproducibility and a strong agreement with AC PET for the assessment of MFR. Non-attenuation-corrected {sup 15}O-water PET provided an accurate measurement of MFR compared to attenuation-corrected PET. However, non-attenuation-corrected PET data were less effective for the assessment of endothelial function using CPT in this population. (orig.)

A novel approach to the assessment of vascular endothelial function

International Nuclear Information System (INIS)

Sathasivam, S; Siddiqui, Z; Greenwald, S; Phababpha, S; Sengmeuan, P; Detchaporn, P; Kukongviriyapan, U

2011-01-01

Impaired endothelial function (EF) is associated with atherogenesis, and its quantitative assessment has prognostic value. Currently, methods based on assessing flow-mediated dilation (FMD) are technically difficult and expensive. We tested a novel way of assessing EF by measuring the time difference between pulses arriving at the middle fingers of each hand (f-fΔT), whilst FMD is induced in one arm. We compared f-fΔT with standard methods in healthy and diseased subjects. Our findings suggest that the proposed simple and inexpensive technique gives comparable results and has the potential to qualitatively assess EF in the clinical setting, although further work is required.

cGMP and nitric oxide modulate thrombin-induced endothelial permeability : Regulation via different pathways in human aortic and umbilical vein endothelial cells

NARCIS (Netherlands)

Draijer, R.; Atsma, D.E.; Laarse, A. van der; Hinsbergh, V.W.M. van

1995-01-01

Previous studies have demonstrated that cGMP and cAMP reduce the endothelial permeability for fluids and macromolecules when the endothelial permeability is increased by thrombin. In this study, we have investigated the mechanism by which cGMP improves the endothelial barrier function and examined

Medical management of venous ulcers.

Science.gov (United States)

Pascarella, Luigi; Shortell, Cynthia K

2015-03-01

Venous disease is the most common cause of chronic leg ulceration and represents an advanced clinical manifestation of venous insufficiency. Due to their frequency and chronicity, venous ulcers have a high socioeconomic impact, with treatment costs accounting for 1% of the health care budget in Western countries. The evaluation of patients with venous ulcers should include a thorough medical history for prior deep venous thrombosis, assessment for an hypercoagulable state, and a physical examination. Use of the CEAP (clinical, etiology, anatomy, pathophysiology) Classification System and the revised Venous Clinical Severity Scoring System is strongly recommended to characterize disease severity and assess response to treatment. This venous condition requires lifestyle modification, with affected individuals performing daily intervals of leg elevation to control edema; use of elastic compression garments; and moderate physical activity, such as walking wearing below-knee elastic stockings. Meticulous skin care, treatment of dermatitis, and prompt treatment of cellulitis are important aspects of medical management. The pharmacology of chronic venous insufficiency and venous ulcers include essentially two medications: pentoxifylline and phlebotropic agents. The micronized purified flavonoid fraction is an effective adjunct to compression therapy in patients with large, chronic ulceration. Copyright © 2015 Elsevier Inc. All rights reserved.

No Evidence of Racial Differences in Endothelial Function and Exercise Blood Flow in Young, Healthy Males Following Acute Antioxidant Supplementation.

Science.gov (United States)

Kappus, Rebecca M; Bunsawat, Kanokwan; Rosenberg, Alexander J; Fernhall, Bo

2017-03-01

This study investigated the effects of acute antioxidant supplementation on endothelial function, exercise blood flow and oxidative stress biomarkers in 9 young African American compared to 10 Caucasian males (25.7±1.2 years). We hypothesized that African American males would have lower exercise blood flow and endothelial responsiveness compared to Caucasian males, and these responses would be improved following antioxidant supplementation. Ultrasonography was used to measure blood flow during handgrip exercise. Endothelial function was assessed using flow-mediated dilation, and lipid peroxidation was assessed by measuring levels of malondialdehyde-thiobarbituric acid reactive substances. African American males exhibited lower endothelial function than Caucasians at baseline (8.3±1.7 vs. 12.2±1.7%) and the difference was ameliorated with antioxidant supplementation (10.7±1.9% vs. 10.8±1.8%), but the interaction was not significant (p=0.10). There were no significant changes in malondialdehyde-thiobarbituric acid reactive substances following antioxidant supplementation. There was a significant increase in brachial blood flow and forearm vascular conductance with exercise but no differences with antioxidant supplementation. There were no group differences in exercise responses and no differences with antioxidant supplementation, suggesting a lack of influence of oxidative stress during exercise in this cohort. © Georg Thieme Verlag KG Stuttgart · New York.

Brain venous pathologies: MRI findings

International Nuclear Information System (INIS)

Salvatico, Rosana; Gonzalez, Alejandro; Yanez, Paulina; Romero, Carlos; Trejo, Mariano; Lambre, Hector

2006-01-01

Purpose: To describe MRI findings of the different brain venous pathologies. Material and Methods: Between January 2002 and March 2004, 18 patients were studied 10 males and 8 females between 6 and 63 years old; with different brain venous pathologies. In all cases brain MRI were performed including morphological sequences with and without gadolinium injection and angiographic venous sequences. Results: 10 venous occlusions were found, 6 venous angiomas, and 2 presented varices secondary to arteriovenous dural fistula. Conclusion: Brain venous pathologies can appear in many different clinical contexts, with different prognosis and treatment. In all the cases brain MRI was the best imaging study to disclose typical morphologic abnormalities. (author) [es

MODERN INSIGHTS INTO THE ROLE OF HEMORHEOLOGICAL DEVIATIONS AND FUNCTIONAL STATUS OF THE ENDOTHELIAL TISSUE IN THE PATHOGENESIS OF ACUTE INFLAMMATORY LUNG AND BRONCHIAL DISEASES AMONG CHILDREN

OpenAIRE

A.V. Mozhaev; R.R. Shilyaev; M.R. Grineva; O.A. Pakhrova

2007-01-01

Disorders of the endothelial tissue and hemorheology function build up one of the pathogenic bases to form the acute inflammatory abnormality of the respiratory tract among children. The overview highlights the information on the role and disorders of the erythrocyte clumping and plasticity, blood viscosity and function of the endothelial tissue as a response to the acute respiratory infections among children.Key words: endothelial dysfunction, hemorheology, hemorheological deviations, acute ...

Cerebral venous angiomas

International Nuclear Information System (INIS)

Agnoli, A.L.; Hildebrandt, G.

1985-01-01

Clinical symptoms and radiological signs in 15 patients with cerebral venous malformations are presented and the diagnostic problems discussed. The circulation time in combination with cerebral malformations and angiomas of the scalp are described. CT findings in cases of venous malformations of the brain stem are evaluated. Spot-like enhancement, as well as sharply demarcated round shaped enhancement are characteristic for venous angiomas. Cavernous angiomas usually present as homogenous or inhomogenous round shaped enhanced areas. (Author)

Impact of high-fat diet and voluntary running on body weight and endothelial function in LDL receptor knockout mice.

Science.gov (United States)

Langbein, Heike; Hofmann, Anja; Brunssen, Coy; Goettsch, Winfried; Morawietz, Henning

2015-05-01

Obesity and physical inactivity are important cardiovascular risk factors. Regular physical exercise has been shown to mediate beneficial effects in the prevention of cardiovascular diseases. However, the impact of physical exercise on endothelial function in proatherosclerotic low-density lipoprotein receptor deficient (LDLR(-/-)) mice has not been studied so far. Six-week-old male LDLR(-/-) mice were fed a standard diet or a high-fat diet (39 kcal% fat diet) for 20 weeks. The impact of high-fat diet and voluntary running on body weight and amount of white adipose tissue was monitored. Basal tone and endothelial function was investigated in aortic rings using a Mulvany myograph. LDLR(-/-) mice on high-fat diet had increased cumulative food energy intake, but also higher physical activity compared to mice on control diet. Body weight and amount of visceral and retroperitoneal white adipose tissue of LDLR(-/-) mice were significantly increased by high-fat diet and partially reduced by voluntary running. Endothelial function in aortae of LDLR(-/-) mice was impaired after 20 weeks on standard and high-fat diet and could not be improved by voluntary running. Basal tone showed a trend to be increased by high-fat diet. Voluntary running reduced body weight and amount of white adipose tissue in LDLR(-/-) mice. Endothelial dysfunction in LDLR(-/-) mice could not be improved by voluntary running. In a clinical context, physical exercise alone might not have an influence on functional parameters and LDL-C levels in patients with familial hypercholesterolemia. However, physical activity in these patients may be in general beneficial and should be performed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Venous ulcers -- self-care

Science.gov (United States)

... surgery to improve blood flow through your veins. Prevention If you are at risk for venous ulcers, take the steps listed above under Wound Care. ... weight if you are overweight. Manage your blood pressure and cholesterol levels. ... Venous leg ulcers - self-care; Venous insufficiency ulcers - self-care; Stasis ...

Ubiquitination of basal VEGFR2 regulates signal transduction and endothelial function

Directory of Open Access Journals (Sweden)

Gina A. Smith

2017-10-01

Full Text Available Cell surface receptors can undergo recycling or proteolysis but the cellular decision-making events that sort between these pathways remain poorly defined. Vascular endothelial growth factor A (VEGF-A and vascular endothelial growth factor receptor 2 (VEGFR2 regulate signal transduction and angiogenesis, but how signaling and proteolysis is regulated is not well understood. Here, we provide evidence that a pathway requiring the E1 ubiquitin-activating enzyme UBA1 controls basal VEGFR2 levels, hence metering plasma membrane receptor availability for the VEGF-A-regulated endothelial cell response. VEGFR2 undergoes VEGF-A-independent constitutive degradation via a UBA1-dependent ubiquitin-linked pathway. Depletion of UBA1 increased VEGFR2 recycling from endosome-to-plasma membrane and decreased proteolysis. Increased membrane receptor availability after UBA1 depletion elevated VEGF-A-stimulated activation of key signaling enzymes such as PLCγ1 and ERK1/2. Although UBA1 depletion caused an overall decrease in endothelial cell proliferation, surviving cells showed greater VEGF-A-stimulated responses such as cell migration and tubulogenesis. Our study now suggests that a ubiquitin-linked pathway regulates the balance between receptor recycling and degradation which in turn impacts on the intensity and duration of VEGF-A-stimulated signal transduction and the endothelial response.

Moderate alcohol consumption is associated with better endothelial function: a cross sectional study

Directory of Open Access Journals (Sweden)

Di Tullio Marco R

2009-02-01

Full Text Available Abstract Background Moderate alcohol consumption is protective against coronary artery disease. Endothelial dysfunction contributes to atherosclerosis and the pathogenesis of cardiovascular disease. The effects of alcohol consumption on endothelial function may be relevant to these cardiovascular outcomes, but very few studies have examined the effect of alcohol consumption on endothelial function assessed by flow-mediated dilation (FMD of the brachial artery in humans. Methods In the population-based Northern Manhattan Study (NOMAS, we performed a cross-sectional analysis of lifetime alcohol intake and brachial artery FMD during reactive hyperemia using high-resolution B-mode ultrasound images among 884 stroke-free participants (mean age 66.8 years, women 56.6%, Hispanic 67.4%, black 17.4%, and white 15.2%. Results The mean brachial FMD was 5.7% and the median was 5.5%. Compared to non-drinkers, those who drank >1 drink/month to 2 drinks/day were more likely to have FMD above the median FMD (5.5% (unadjusted OR 1.7, 95% CI 1.2–2.4, p = 0.005. In multivariate analysis, the relationship between moderate alcohol consumption and FMD remained significant after adjusting for multiple traditional cardiovascular risk factors, including sex, race-ethnicity, body mass index, diabetes mellitus, coronary artery disease, Framingham risk score, medication use (adjusted OR 1.8, 95%CI 1.1–3.0, p = 0.03. No beneficial effect on FMD was seen for those who drank more than 2 drinks/day. Conclusion In conclusion, consumption of up to 2 alcoholic beverages per day was independently associated with better FMD compared to no alcohol consumption in this multiethnic population. This effect on FMD may represent an important mechanism in explaining the protective effect of alcohol intake on cardiovascular disease.

Olfactory evaluation in Mild Cognitive Impairment: correlation with neurocognitive performance and endothelial function.

Science.gov (United States)

Tonacci, Alessandro; Bruno, Rosa M; Ghiadoni, Lorenzo; Pratali, Lorenza; Berardi, Nicoletta; Tognoni, Gloria; Cintoli, Simona; Volpi, Leda; Bonuccelli, Ubaldo; Sicari, Rosa; Taddei, Stefano; Maffei, Lamberto; Picano, Eugenio

2017-05-01

Mild Cognitive Impairment (MCI) is an intermediate condition between normal aging and dementia, associated with an increased risk of progression into the latter within months or years. Olfactory impairment, a well-known biomarker for neurodegeneration, might be present in the condition early, possibly representing a signal for future pathological onset. Our study aimed at evaluating olfactory function in MCI and healthy controls in relation to neurocognitive performance and endothelial function. A total of 85 individuals with MCI and 41 healthy controls, matched for age and gender, were recruited. Olfactory function was assessed by Sniffin' Sticks Extended Test (Burghart, Medizintechnik, GmbH, Wedel, Germany). A comprehensive neurocognitive assessment was performed. Endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery by ultrasound. MCI individuals showed an impaired olfactory function compared to controls. The overall olfactory score is able to predict MCI with a good sensitivity and specificity (70.3 and 77.4% respectively). In MCI, olfactory identification score is correlated with a number of neurocognitive abilities, including overall cognitive status, dementia rating, immediate and delayed memory, visuospatial ability and verbal fluency. FMD was reduced in MCI (2.90 ± 2.15 vs. 3.66 ± 1.96%, P = 0.016) and was positively associated with olfactory identification score (ρ s =0.219, P = 0.025). The association remained significant after controlling for age, gender, and smoking. In conclusion, olfactory evaluation is able to discriminate between MCI and healthy individuals. Systemic vascular dysfunction might be involved, at least indirectly, in olfactory dysfunction in MCI. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Curcumin modulates endothelial permeability and monocyte transendothelial migration by affecting endothelial cell dynamics.

Science.gov (United States)

Monfoulet, Laurent-Emmanuel; Mercier, Sylvie; Bayle, Dominique; Tamaian, Radu; Barber-Chamoux, Nicolas; Morand, Christine; Milenkovic, Dragan

2017-11-01

Curcumin is a phenolic compound that exhibits beneficial properties for cardiometabolic health. We previously showed that curcumin reduced the infiltration of immune cells into the vascular wall and prevented atherosclerosis development in mice. This study aimed to investigate the effect of curcumin on monocyte adhesion and transendothelial migration (TEM) and to decipher the underlying mechanisms of these actions. Human umbilical vein endothelial cells (HUVECs) were exposed to curcumin (0.5-1μM) for 3h prior to their activation by Tumor Necrosis Factor alpha (TNF-α). Endothelial permeability, monocyte adhesion and transendothelial migration assays were conducted under static condition and shear stress that mimics blood flow. We further investigated the impact of curcumin on signaling pathways and on the expression of genes using macroarrays. Pre-exposure of endothelial cells to curcumin reduced monocyte adhesion and their transendothelial migration in both static and shear stress conditions. Curcumin also prevented changes in both endothelial permeability and the area of HUVECs when induced by TNF-α. We showed that curcumin modulated the expression of 15 genes involved in the control of cytoskeleton and endothelial junction dynamic. Finally, we showed that curcumin inhibited NF-κB signaling likely through an antagonist interplay with several kinases as suggested by molecular docking analysis. Our findings demonstrate the ability of curcumin to reduce monocyte TEM through a multimodal regulation of the endothelial cell dynamics with a potential benefit on the vascular endothelial function barrier. Copyright © 2017 Elsevier Inc. All rights reserved.

Sarcopenia and Endothelial Function in Patients With Chronic Heart Failure: Results From the Studies Investigating Comorbidities Aggravating Heart Failure (SICA-HF).

Science.gov (United States)

Dos Santos, Marcelo R; Saitoh, Masakazu; Ebner, Nicole; Valentova, Miroslava; Konishi, Masaaki; Ishida, Junichi; Emami, Amir; Springer, Jochen; Sandek, Anja; Doehner, Wolfram; Anker, Stefan D; von Haehling, Stephan

2017-03-01

Skeletal muscle wasting, also known as sarcopenia, has recently been identified as a serious comorbidity in patients with heart failure (HF). We aimed to assess the impact of sarcopenia on endothelial dysfunction in patients with HF with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF). Cross-sectional study. Ambulatory patients with HF were recruited at Charité Medical School, Campus Virchow-Klinikum, Berlin, Germany. We assessed peripheral blood flow (arm and leg) in 228 patients with HF and 32 controls who participated in the Studies Investigating Comorbidities Aggravating HF (SICA-HF). The appendicular skeletal muscle mass of the arms and the legs combined was assessed by dual energy x-ray absorptiometry (DEXA). Sarcopenia was defined as the appendicular muscle mass two standard deviations below the mean of a healthy reference group of adults aged 18 to 40 years, as suggested for the diagnosis of muscle wasting in healthy aging. All patients underwent a 6-minute walk test and spiroergometry testing. Forearm and leg blood flow were measured by venous occlusion plethysmography. Peak blood flow was assessed after a period of ischemia in the limbs to test endothelial function. Sarcopenia was identified in 37 patients (19.5%). Patients with sarcopenia presented with lower baseline forearm blood flow (2.30 ± 1.21 vs. 3.06 ± 1.49 vs. 4.00 ± 1.66 mL min -1 100 mL -1 ; P = .02) than those without sarcopenia or controls. The group of patients with sarcopenia showed similar baseline leg blood flow (2.06 ± 1.62 vs. 2.39 ± 1.39 mL min -1 100 mL -1 ; P = .11) to those without but lower values when compared to controls (2.06 ± 1.62 vs. 2.99 ± 1.28 mL min -1 100 mL -1 ; P = .03). In addition, patients with and without sarcopenia presented with lower peak flow in the forearm when compared to controls (18.37 ± 7.07 vs. 22.19 ± 8.64 vs. 33.63 ± 8.57 mL min -1 100 mL -1 ; P sarcopenia, and coronary artery

Three-dimensional culture conditions differentially affect astrocyte modulation of brain endothelial barrier function in response to transforming growth factor β1.

Science.gov (United States)

Hawkins, Brian T; Grego, Sonia; Sellgren, Katelyn L

2015-05-22

Blood-brain barrier (BBB) function is regulated by dynamic interactions among cell types within the neurovascular unit, including astrocytes and endothelial cells. Co-culture models of the BBB typically involve astrocytes seeded on two-dimensional (2D) surfaces, which recent studies indicate cause astrocytes to express a phenotype similar to that of reactive astrocytes in situ. We hypothesized that the culture conditions of astrocytes would differentially affect their ability to modulate BBB function in vitro. Brain endothelial cells were grown alone or in co-culture with astrocytes. Astrocytes were grown either as conventional (2D) monolayers, or in a collagen-based gel which allows them to grow in a three-dimensional (3D) construct. Astrocytes were viable in 3D conditions, and displayed a marked reduction in their expression of glial fibrillary acidic protein (GFAP), suggesting reduced activation. Stimulation of astrocytes with transforming growth factor (TGF)β1 decreased transendothelial electrical resistance (TEER) and reduced expression of claudin-5 in co-cultures, whereas treatment of endothelial cells in the absence of astrocytes was without effect. The effect of TGFβ1 on TEER was significantly more pronounced in endothelial cells cultured with 3D astrocytes compared to 2D astrocytes. These results demonstrate that astrocyte culture conditions differentially affect their ability to modulate brain endothelial barrier function, and suggest a direct relationship between reactive gliosis and BBB permeability. Moreover, these studies demonstrate the potential importance of physiologically relevant culture conditions to in vitro modeling of disease processes that affect the neurovascular unit. Copyright © 2015 Elsevier B.V. All rights reserved.

Endothelial Protein C–Targeting Liposomes Show Enhanced Uptake and Improved Therapeutic Efficacy in Human Retinal Endothelial Cells

DEFF Research Database (Denmark)

Arta, Anthoula; Eriksen, Anne Z.; Melander, Fredrik

2018-01-01

PURPOSE. To determine whether human retinal endothelial cells (HRECs) express the endothelial cell protein C receptor (EPCR) and to realize its potential as a targeting moiety by developing novel single and dual corticosteroid–loaded functionalized liposomes that exhibit both enhanced uptake by H...... of cell tube formations in contrast to nontargeting liposomes. CONCLUSIONS. We show that HRECs express EPCR and this receptor could be a promising nanomedicine target in ocular diseases where the endothelial barrier of the retina is compromised....

Models of the venous system

DEFF Research Database (Denmark)

Mehlsen, J

2000-01-01

Cardiac output is largely controlled by venous return, the driving force of which is the energy remaining at the postcapillary venous site. This force is influenced by forces acting close to the right atrium, and internally or externally upon the veins along their course. Analogue models of the v......Cardiac output is largely controlled by venous return, the driving force of which is the energy remaining at the postcapillary venous site. This force is influenced by forces acting close to the right atrium, and internally or externally upon the veins along their course. Analogue models...... of the venous system require at least three elements: a resistor, a capacitor and an inductor, with the latter being of more importance in the venous than in the arterial system. Non-linearities must be considered in pressure/flow relations in the small venules, during venous collapse, or low flow conditions...

Catalase and superoxide dismutase conjugated with platelet-endothelial cell adhesion molecule antibody distinctly alleviate abnormal endothelial permeability caused by exogenous reactive oxygen species and vascular endothelial growth factor.

Science.gov (United States)

Han, Jingyan; Shuvaev, Vladimir V; Muzykantov, Vladimir R

2011-07-01

Reactive oxygen species (ROS) superoxide anion (O(2)()) and hydrogen peroxide (H(2)O(2)) produced by activated leukocytes and endothelial cells in sites of inflammation or ischemia cause endothelial barrier dysfunction that may lead to tissue edema. Antioxidant enzymes (AOEs) catalase and superoxide dismutase (SOD) conjugated with antibodies to platelet-endothelial cell adhesion molecule-1 (PECAM-1) specifically bind to endothelium, quench the corresponding ROS, and alleviate vascular oxidative stress and inflammation. In the present work, we studied the effects of anti-PECAM/catalase and anti-PECAM/SOD conjugates on the abnormal permeability manifested by transendothelial electrical resistance decline, increased fluorescein isothiocyanate-dextran influx, and redistribution of vascular endothelial-cadherin in human umbilical vein endothelial cell (HUVEC) monolayers. Anti-PECAM/catalase protected HUVEC monolayers against H(2)O(2)-induced endothelial barrier dysfunction. Polyethylene glycol-conjugated catalase exerted orders of magnitude lower endothelial uptake and no protective effect, similarly to IgG/catalase. Anti-PECAM/catalase, but not anti-PECAM/SOD, alleviated endothelial hyperpermeability caused by exposure to hypoxanthine/xanthine oxidase, implicating primarily H(2)O(2) in the disruption of the endothelial barrier in this model. Thrombin-induced endothelial permeability was not affected by treatment with anti-PECAM/AOEs or the NADPH oxidase inhibitor apocynin or overexpression of AOEs, indicating that the endogenous ROS play no key role in thrombin-mediated endothelial barrier dysfunction. In contrast, anti-PECAM/SOD, but not anti-PECAM/catalase, inhibited a vascular endothelial growth factor (VEGF)-induced increase in endothelial permeability, identifying a key role of endogenous O(2)() in the VEGF-mediated regulation of endothelial barrier function. Therefore, AOEs targeted to endothelial cells provide versatile molecular tools for testing the roles of

Long-term effects of bariatric surgery on peripheral endothelial function and coronary microvascular function.

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Tarzia, Pierpaolo; Lanza, Gaetano A; Sestito, Alfonso; Villano, Angelo; Russo, Giulio; Figliozzi, Stefano; Lamendola, Priscilla; De Vita, Antonio; Crea, Filippo

We previously demonstrated that bariatric surgery (BS) leads to a short-term significant improvement of endothelial function and coronary microvascular function. In this study we assessed whether BS maintains its beneficial effect at long-term follow up. We studied 19 morbidly obese patients (age 43±9years, 12 women) without any evidence of cardiovascular disease who underwent BS. Patients were studied before BS, at 3 months and at 4.0±1.5years follow up. Peripheral vascular function was assessed by flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD), i.e., brachial artery diameter changes in response to post-ischemic forearm hyperhaemia and to nitroglycerin administration, respectively. Coronary microvascular function was assessed by measuring coronary blood flow (CBF) response to intravenous adenosine and to cold pressor test (CPT) in the left anterior descending coronary artery. Together with improvement of anthropometric and metabolic profile, at long-term follow-up patients showed a significant improvement of FMD (6.43±2.88 vs. 8.21±1.73%, p=0.018), and CBF response to both adenosine (1.73±0.48 vs. 2.58±0.54; pfunction and on coronary microvascular dilator function. Copyright © 2016 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Normal endothelial function after meals rich in olive or safflower oil previously used for deep frying.

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Williams, M J; Sutherland, W H; McCormick, M P; Yeoman, D; de Jong, S A; Walker, R J

2001-06-01

Polyunsaturated fats are more susceptible to oxidation during heating than monounsaturated fats but their effects on endothelial function when heated are unknown. The aim of this study was to compare the effect of meals rich in heat-modified safflower and olive oils on postprandial flow-mediated endothelium-dependent dilation (EDD) in healthy men. Flow-mediated EDD and glyceryltrinitrate-induced endothelium-independent dilation of the brachial artery were investigated in 14 subjects before and 4 hours after meals rich in olive oil and safflower oil used hourly for deep-frying for 8 hours in a double-blind crossover study design. There were high levels of lipid oxidation products (peroxides and carbonyls) in both heated oils. Plasma triglycerides were markedly increased at 4 hours after heated olive oil (1.26 +/- 0.43 vs 2.06 +/- 0.97 mmol/L) and heated safflower oil (1.44 +/- 0.63 vs 1.99 +/- 0.88 mmol/L). There was no change in EDD between fasting and postprandial studies and the response during the postprandial period was not significantly (p = 0.51) different between the meals (heated olive oil: 4.9 +/- 2.2% vs 4.9 +/- 2.5%; heated safflower oil: 5.1 +/- 3.1% vs 5.6 +/- 3.4%). Meals rich in olive and safflower oils previously used for deep frying and containing high levels of lipid oxidation products increase postprandial serum triglycerides without affecting endothelial function. These findings suggest that relatively short-term use of these vegetable oils for frying may not adversely affect postprandial endothelial function when foods containing the heat-modified oils are consumed.

Venous, Arterialized-Venous, or Capillary Glucose Reference Measurements for the Accuracy Assessment of a Continuous Glucose Monitoring System.

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Kropff, Jort; van Steen, Sigrid C; deGraaff, Peter; Chan, Man W; van Amstel, Rombout B E; DeVries, J Hans

2017-11-01

Different reference methods are used for the accuracy assessment of continuous glucose monitoring (CGM) systems. The effect of using venous, arterialized-venous, or capillary reference measurements on CGM accuracy is unclear. We evaluated 21 individuals with type 1 diabetes using a capillary calibrated CGM system. Venous or arterialized-venous reference glucose samples were taken every 15 min at two separate visits and assessed per YSI 2300 STAT Plus. Arterialization was achieved by heated-hand technique. Capillary samples were collected hourly during the venous reference visit. The investigation sequence (venous or arterialized-venous) was randomized. Effectiveness of arterialization was measured by comparing free venous oxygen pressure (PO2) of both visit days. Primary endpoint was the median absolute relative difference (ARD). Median ARD using arterialized-venous reference samples was not different from venous samples (point estimated difference 0.52%, P = 0.181). When comparing the three reference methods, median ARD was also not different over the full glycemic range (venous 9.0% [n = 681], arterialized-venous 8.3% [n = 684], and capillary 8.1% [n = 205], P = 0.216), nor over the separate glucose ranges. Arterialization was successful (PO2 venous 5.4 kPa vs. arterialized-venous 8.9 kPa, P reference measurements did not significantly impact CGM accuracy. Venous reference seems preferable due to its ease of operation.

Telmisartan activates endothelial nitric oxide synthase via Ser1177 phosphorylation in vascular endothelial cells.

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Masahiro Myojo

Full Text Available Because endothelial nitric oxide synthase (eNOS has anti-inflammatory and anti-arteriosclerotic functions, it has been recognized as one of the key molecules essential for the homeostatic control of blood vessels other than relaxation of vascular tone. Here, we examined whether telmisartan modulates eNOS function through its pleiotropic effect. Administration of telmisartan to mice significantly increased the phosphorylation level of eNOS (Ser1177 in the aortic endothelium, but administration of valsartan had no effect. Similarly, telmisartan treatment of human umbilical vein endothelial cells significantly increased the phosphorylation levels of AMP-activated protein kinase (Thr172 and eNOS and the concentration of intracellular guanosine 3',5'-cyclic monophosphate (cGMP. Furthermore, pretreatment with a p38 mitogen-activated protein kinase (p38 MAPK inhibitor suppressed the increased phosphorylation level of eNOS and intracellular cGMP concentration. These data show that telmisartan increases eNOS activity through Ser1177 phosphorylation in vascular endothelial cells mainly via p38 MAPK signaling.

Flow shear stress differentially regulates endothelial uptake of nanocarriers targeted to distinct epitopes of PECAM-1.

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Han, Jingyan; Shuvaev, Vladimir V; Davies, Peter F; Eckmann, David M; Muro, Silvia; Muzykantov, Vladimir R

2015-07-28

Targeting nanocarriers (NC) to endothelial cell adhesion molecules including Platelet-Endothelial Cell Adhesion Molecule-1 (PECAM-1 or CD31) improves drug delivery and pharmacotherapy of inflammation, oxidative stress, thrombosis and ischemia in animal models. Recent studies unveiled that hydrodynamic conditions modulate endothelial endocytosis of NC targeted to PECAM-1, but the specificity and mechanism of effects of flow remain unknown. Here we studied the effect of flow on endocytosis by human endothelial cells of NC targeted by monoclonal antibodies Ab62 and Ab37 to distinct epitopes on the distal extracellular domain of PECAM. Flow in the range of 1-8dyn/cm(2), typical for venous vasculature, stimulated the uptake of spherical Ab/NC (~180nm diameter) carrying ~50 vs 200 Ab62 and Ab37 per NC, respectively. Effect of flow was inhibited by disruption of cholesterol-rich plasmalemma domains and deletion of PECAM-1 cytosolic tail. Flow stimulated endocytosis of Ab62/NC and Ab37/NC via eliciting distinct signaling pathways mediated by RhoA/ROCK and Src Family Kinases, respectively. Therefore, flow stimulates endothelial endocytosis of Ab/NC in a PECAM-1 epitope specific manner. Using ligands of binding to distinct epitopes on the same target molecule may enable fine-tuning of intracellular delivery based on the hemodynamic conditions in the vascular area of interest. Copyright © 2015 Elsevier B.V. All rights reserved.

The Role of Inflammation in Venous Thromboembolism

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Brian R. Branchford

2018-05-01

Full Text Available Venous thromboembolism (VTE, comprising deep vein thrombosis (DVT, and pulmonary embolism (PE, is becoming increasingly recognized as a cause of morbidity and mortality in pediatrics, particularly among hospitalized children. Furthermore, evidence is accumulating that suggests the inflammatory response may be a cause, as well as consequence, of VTE, but current anticoagulation treatment regimens are not designed to inhibit inflammation. In fact, many established clinical VTE risk factors such as surgery, obesity, cystic fibrosis, sepsis, systemic infection, cancer, inflammatory bowel disease, and lupus likely modulate thrombosis through inflammatory mediators. Unlike other traumatic mechanisms of thrombosis involving vascular transection and subsequent exposure of subendothelial collagen and other procoagulant extracellular matrix materials, inflammation of the vessel wall may initiate thrombosis on an intact vein. Activation of endothelial cells, platelets, and leukocytes with subsequent formation of microparticles can trigger the coagulation system through the induction of tissue factor (TF. Identification of biomarkers to evaluate VTE risk could be of great use to the clinician caring for a patient with inflammatory disease to guide decisions regarding the risk:benefit ratio of various types of potential thromboprophylaxis strategies, or suggest a role for anti-inflammatory therapy. Unfortunately, no such validated inflammatory scoring system yet exists, though research in this area is ongoing. Elevation of C-reactive protein, IL-6, IL-8, and TNF-alpha during a response to systemic inflammation have been associated with increased VTE risk. Consequent platelet activation enhances the prothrombotic state, leading to VTE development, particularly in patients with other risk factors, most notably central venous catheters.

MODERN INSIGHTS INTO THE ROLE OF HEMORHEOLOGICAL DEVIATIONS AND FUNCTIONAL STATUS OF THE ENDOTHELIAL TISSUE IN THE PATHOGENESIS OF ACUTE INFLAMMATORY LUNG AND BRONCHIAL DISEASES AMONG CHILDREN

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A.V. Mozhaev

2007-01-01

Full Text Available Disorders of the endothelial tissue and hemorheology function build up one of the pathogenic bases to form the acute inflammatory abnormality of the respiratory tract among children. The overview highlights the information on the role and disorders of the erythrocyte clumping and plasticity, blood viscosity and function of the endothelial tissue as a response to the acute respiratory infections among children.Key words: endothelial dysfunction, hemorheology, hemorheological deviations, acute respiratory infections, acute bronchopulmonary diseases, children.

Ubiquitination of basal VEGFR2 regulates signal transduction and endothelial function.

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Smith, Gina A; Fearnley, Gareth W; Abdul-Zani, Izma; Wheatcroft, Stephen B; Tomlinson, Darren C; Harrison, Michael A; Ponnambalam, Sreenivasan

2017-10-15

Cell surface receptors can undergo recycling or proteolysis but the cellular decision-making events that sort between these pathways remain poorly defined. Vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor receptor 2 (VEGFR2) regulate signal transduction and angiogenesis, but how signaling and proteolysis is regulated is not well understood. Here, we provide evidence that a pathway requiring the E1 ubiquitin-activating enzyme UBA1 controls basal VEGFR2 levels, hence metering plasma membrane receptor availability for the VEGF-A-regulated endothelial cell response. VEGFR2 undergoes VEGF-A-independent constitutive degradation via a UBA1-dependent ubiquitin-linked pathway. Depletion of UBA1 increased VEGFR2 recycling from endosome-to-plasma membrane and decreased proteolysis. Increased membrane receptor availability after UBA1 depletion elevated VEGF-A-stimulated activation of key signaling enzymes such as PLCγ1 and ERK1/2. Although UBA1 depletion caused an overall decrease in endothelial cell proliferation, surviving cells showed greater VEGF-A-stimulated responses such as cell migration and tubulogenesis. Our study now suggests that a ubiquitin-linked pathway regulates the balance between receptor recycling and degradation which in turn impacts on the intensity and duration of VEGF-A-stimulated signal transduction and the endothelial response. © 2017. Published by The Company of Biologists Ltd.

Animal study on transplantation of human umbilical vein endothelial cells for corneal endothelial decompensation

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Li Cui

2014-06-01

Full Text Available AIM: To explore the feasibility of culturing human umbilical vein endothelial cells(HUVECon acellular corneal stroma and performing the posterior lamellar endothelial keratoplasty(PLEKtreating corneal endothelial decompensation.METHODS: Thirty New-Zealand rabbits were divided into three groups randomly, 10 rabbits for experimental group, 10 for stroma group and 10 for control group. Corneal endothelial cells were removed to establish animal model of corneal endothelial failure. PLEK was performed on the rabbits of experimental group and stroma group, and nothing was transplantated onto the rabbits of control group with the deep layer excised only. Postoperative observation was taken for 3mo. The degree of corneal edema and central corneal thickness were recorded for statistical analysis.RESULTS: Corneas in experimental group were relieved in edema obviously compared with that in stroma group and the control group, and showed increased transparency 7d after the operation. The average density of endothelial cells was 2 026.4±129.3cells/mm2, and average central corneal thickness was 505.2±25.4μm in experimental group, while 1 535.6±114.5μm in stroma group and 1 493.5±70.2μm in control group 3mo after operation.CONCLUSION:We achieved preliminary success in our study that culturing HUVEC on acellular corneal stroma and performing PLEK for corneal endothelial decompensation. HUVEC transplanted could survive in vivo, and have normal biological function of keeping cornea transparent. This study provides a new idea and a new way clinically for the treatment of corneal endothelial diseases.

Flavonoid-rich apples and nitrate-rich spinach augment nitric oxide status and improve endothelial function in healthy men and women: a randomized controlled trial.

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Bondonno, Catherine P; Yang, Xingbin; Croft, Kevin D; Considine, Michael J; Ward, Natalie C; Rich, Lisa; Puddey, Ian B; Swinny, Ewald; Mubarak, Aidilla; Hodgson, Jonathan M

2012-01-01

Flavonoids and nitrates in fruits and vegetables may protect against cardiovascular disease. Dietary flavonoids and nitrates can augment nitric oxide status via distinct pathways, which may improve endothelial function and lower blood pressure. Recent studies suggest that the combination of flavonoids and nitrates can enhance nitric oxide production in the stomach. Their combined effect in the circulation is unclear. Here, our objective was to investigate the independent and additive effects of flavonoid-rich apples and nitrate-rich spinach on nitric oxide status, endothelial function, and blood pressure. A randomized, controlled, crossover trial with healthy men and women (n=30) was conducted. The acute effects of four energy-matched treatments (control, apple, spinach, and apple+spinach), administered in random order, were compared. Measurements included plasma nitric oxide status, assessed by measuring S-nitrosothiols+other nitrosylated species (RXNO) and nitrite, blood pressure, and endothelial function, measured as flow-mediated dilatation of the brachial artery. Results are means and 95% CI. Relative to control, all treatments resulted in higher RXNO (control, 33 nmol/L, 26, 42; apple, 51 nmol/L, 40, 65; spinach, 86 nmol/L, 68, 110; apple+spinach, 69 nmol/L, 54, 88; Pflow-mediated dilatation (Peffect was observed on diastolic blood pressure. The combination of apple and spinach did not result in additive effects on nitric oxide status, endothelial function, or blood pressure. In conclusion, flavonoid-rich apples and nitrate-rich spinach can independently augment nitric oxide status, enhance endothelial function, and lower blood pressure acutely, outcomes that may benefit cardiovascular health. Copyright © 2011 Elsevier Inc. All rights reserved.

Effect of Intermittent Energy Restriction on Flow Mediated Dilatation, a Measure of Endothelial Function: A Short Report

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Michelle L. Headland

2018-06-01

Full Text Available Intermittent energy restriction is a popular alternative to daily energy restriction for weight loss; however, it is unknown if endothelial function, a risk factor for cardiovascular disease, is altered by periods of severe energy restriction. The objective of the study was to determine the impact of two consecutive very low energy intake days, which is the core component of the 5:2 intermittent energy restriction diet strategy, on endothelial function compared to consecutive ad libitum eating days. The secondary objective was to explore the effects of these dietary conditions on fasting glucose concentrations. This was a 4-week randomized, single-blinded, crossover study of 35 participants. Participants consumed a very low energy diet (500 calories for women, 600 calories for men on two consecutive days per week and 5 days of habitual eating. In weeks 3 and 4 of the trial, participants had measurements of flow mediated dilatation (FMD and blood samples taken following either 2 habitual eating days or 2 energy restricted days in a randomized order. FMD values were not different after the two eating states (8.6% vs. 8.3%, p = 0.7. All other outcome variables were unchanged. Endothelial function, as measured by flow mediated dilatation, was not altered by two consecutive very low energy intake days. Further investigations assessing the impact in specific population groups as well as different testing conditions would be beneficial.

Effect of Functional Bread Rich in Potassium, γ-Aminobutyric Acid and Angiotensin-Converting Enzyme Inhibitors on Blood Pressure, Glucose Metabolism and Endothelial Function

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Becerra-Tomás, Nerea; Guasch-Ferré, Marta; Quilez, Joan; Merino, Jordi; Ferré, Raimon; Díaz-López, Andrés; Bulló, Mònica; Hernández-Alonso, Pablo; Palau-Galindo, Antoni; Salas-Salvadó, Jordi

2015-01-01

Abstract Because it has been suggested that food rich in γ-aminobutyric acid (GABA) or angiotensin-converting enzyme inhibitor (ACEI) peptides have beneficial effects on blood pressure (BP) and other cardiovascular risk factors, we tested the effects of low-sodium bread, but rich in potassium, GABA, and ACEI peptides on 24-hour BP, glucose metabolism, and endothelial function. A randomized, double-blind, crossover trial was conducted in 30 patients with pre or mild-to-moderate hypertension, comparing three 4-week nutritional interventions separated by 2-week washout periods. Patients were randomly assigned to consume 120 g/day of 1 of the 3 types of bread for each nutritional intervention: conventional wheat bread (CB), low-sodium wheat bread enriched in potassium (LSB), and low-sodium wheat bread rich in potassium, GABA, and ACEI peptides (LSB + G). For each period, 24-hour BP measurements, in vivo endothelial function, and biochemical samples were obtained. After LSB + G consumption, 24-hour ambulatory BP underwent a nonsignificant greater reduction than after the consumption of CB and LSB (0.26 mm Hg in systolic BP and −0.63 mm Hg in diastolic BP for CB; −0.71 mm Hg in systolic BP and −1.08 mm Hg in diastolic BP for LSB; and −0.75 mm Hg in systolic BP and −2.12 mm Hg in diastolic BP for LSB + G, respectively). Diastolic BP at rest decreased significantly during the LSB + G intervention, although there were no significant differences in changes between interventions. There were no significant differences between interventions in terms of changes in in vivo endothelial function, glucose metabolism, and peripheral inflammatory parameters. Compared with the consumption of CB or LSB, no greater beneficial effects on 24-hour BP, endothelial function, or glucose metabolism were demonstrated after the consumption of LSB + G in a population with pre or mild-to-moderate hypertension. Further studies are warranted to clarify the

Vascular endothelial growth factor A-stimulated signaling from endosomes in primary endothelial cells.

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Fearnley, Gareth W; Smith, Gina A; Odell, Adam F; Latham, Antony M; Wheatcroft, Stephen B; Harrison, Michael A; Tomlinson, Darren C; Ponnambalam, Sreenivasan

2014-01-01

The vascular endothelial growth factor A (VEGF-A) is a multifunctional cytokine that stimulates blood vessel sprouting, vascular repair, and regeneration. VEGF-A binds to VEGF receptor tyrosine kinases (VEGFRs) and stimulates intracellular signaling leading to changes in vascular physiology. An important aspect of this phenomenon is the spatiotemporal coordination of VEGFR trafficking and intracellular signaling to ensure that VEGFR residence in different organelles is linked to downstream cellular outputs. Here, we describe a series of assays to evaluate the effects of VEGF-A-stimulated intracellular signaling from intracellular compartments such as the endosome-lysosome system. These assays include the initial isolation and characterization of primary human endothelial cells, performing reverse genetics for analyzing protein function; methods used to study receptor trafficking, signaling, and proteolysis; and assays used to measure changes in cell migration, proliferation, and tubulogenesis. Each of these assays has been exemplified with studies performed in our laboratories. In conclusion, we describe necessary techniques for studying the role of VEGF-A in endothelial cell function. © 2014 Elsevier Inc. All rights reserved.

Characterisation of hypertensive patients with improved endothelial function after dark chocolate consumption.

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d'El-Rei, Jenifer; Cunha, Ana Rosa; Burlá, Adriana; Burlá, Marcelo; Oigman, Wille; Neves, Mario Fritsch; Virdis, Agostino; Medeiros, Fernanda

2013-01-01

Recent findings indicate an inverse relationship between cardiovascular disease and consumption of flavonoids. We aimed to identify clinical and vascular parameters of treated hypertensive who present beneficial effects of dark chocolate for one-week period on vascular function. Twenty-one hypertensive subjects, aged 40-65 years, were included in a prospective study with measurement of blood pressure (BP), brachial flow-mediated dilatation (FMD), peripheral arterial tonometry, and central hemodynamic parameters. These tests were repeated after seven days of eating dark chocolate 75 g/day. Patients were divided according to the response in FMD: responders (n = 12) and nonresponders (n = 9). The responder group presented lower age (54 ± 7 versus 61 ± 6 years, P = 0.037), Framingham risk score (FRS) (2.5 ± 1.8 versus 8.1 ± 5.1%, P = 0.017), values of peripheral (55 ± 9 versus 63 ± 5 mmHg, P = 0.041), and central pulse pressure (PP) (44 ± 10 versus 54 ± 6 mmHg, P = 0.021). FMD response showed negative correlation with FRS (r = -0.60, P = 0.014), baseline FMD (r = -0.54, P = 0.011), baseline reactive hyperemia index (RHI; r = -0.56, P = 0.008), and central PP (r = -0.43, P = 0.05). However, after linear regression analysis, only FRS and baseline RHI were associated with FMD response. In conclusion, one-week dark chocolate intake significantly improved endothelial function and reduced BP in younger hypertensive with impaired endothelial function in spite of lower cardiovascular risk.

Characterisation of Hypertensive Patients with Improved Endothelial Function after Dark Chocolate Consumption

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Jenifer d'El-Rei

2013-01-01

Full Text Available Recent findings indicate an inverse relationship between cardiovascular disease and consumption of flavonoids. We aimed to identify clinical and vascular parameters of treated hypertensive who present beneficial effects of dark chocolate for one-week period on vascular function. Twenty-one hypertensive subjects, aged 40–65 years, were included in a prospective study with measurement of blood pressure (BP, brachial flow-mediated dilatation (FMD, peripheral arterial tonometry, and central hemodynamic parameters. These tests were repeated after seven days of eating dark chocolate 75 g/day. Patients were divided according to the response in FMD: responders (n=12 and nonresponders (n=9. The responder group presented lower age (54 ± 7 versus 61 ± 6 years, P=0.037, Framingham risk score (FRS (2.5 ± 1.8 versus 8.1 ± 5.1%, P=0.017, values of peripheral (55 ± 9 versus 63 ± 5 mmHg, P=0.041, and central pulse pressure (PP (44 ± 10 versus 54 ± 6 mmHg, P=0.021. FMD response showed negative correlation with FRS (r=−0.60, P=0.014, baseline FMD (r=−0.54, P=0.011, baseline reactive hyperemia index (RHI; r=−0.56, P=0.008, and central PP (r=−0.43, P=0.05. However, after linear regression analysis, only FRS and baseline RHI were associated with FMD response. In conclusion, one-week dark chocolate intake significantly improved endothelial function and reduced BP in younger hypertensive with impaired endothelial function in spite of lower cardiovascular risk.

Characterisation of Hypertensive Patients with Improved Endothelial Function after Dark Chocolate Consumption

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d'El-Rei, Jenifer; Cunha, Ana Rosa; Burlá, Adriana; Burlá, Marcelo; Oigman, Wille

2013-01-01

Recent findings indicate an inverse relationship between cardiovascular disease and consumption of flavonoids. We aimed to identify clinical and vascular parameters of treated hypertensive who present beneficial effects of dark chocolate for one-week period on vascular function. Twenty-one hypertensive subjects, aged 40–65 years, were included in a prospective study with measurement of blood pressure (BP), brachial flow-mediated dilatation (FMD), peripheral arterial tonometry, and central hemodynamic parameters. These tests were repeated after seven days of eating dark chocolate 75 g/day. Patients were divided according to the response in FMD: responders (n = 12) and nonresponders (n = 9). The responder group presented lower age (54 ± 7 versus 61 ± 6 years, P = 0.037), Framingham risk score (FRS) (2.5 ± 1.8 versus 8.1 ± 5.1%, P = 0.017), values of peripheral (55 ± 9 versus 63 ± 5 mmHg, P = 0.041), and central pulse pressure (PP) (44 ± 10 versus 54 ± 6 mmHg, P = 0.021). FMD response showed negative correlation with FRS (r = −0.60, P = 0.014), baseline FMD (r = −0.54, P = 0.011), baseline reactive hyperemia index (RHI; r = −0.56, P = 0.008), and central PP (r = −0.43, P = 0.05). However, after linear regression analysis, only FRS and baseline RHI were associated with FMD response. In conclusion, one-week dark chocolate intake significantly improved endothelial function and reduced BP in younger hypertensive with impaired endothelial function in spite of lower cardiovascular risk. PMID:23533716

Comparative effects of enzogenol and vitamin C supplementation versus vitamin C alone on endothelial function and biochemical markers of oxidative stress and inflammation in chronic smokers.

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Young, Joanna M; Shand, Brett I; McGregor, Patrice M; Scott, Russell S; Frampton, Christopher M

2006-01-01

Chronic smoking is associated with endothelial dysfunction and inflammation, with oxidative stress contributing to both these processes. In this study, we investigated the effect of combined antioxidant treatment with Enzogenol, a flavonoid extract from the bark of Pinus radiata and vitamin C, over and above vitamin C alone, on endothelial function, plasma markers of inflammation and oxidative stress, blood pressure (BP) and anthropometrics. Forty-four chronic smokers without established cardiovascular disease were assigned randomly to receive either 480 mg Enzogenol and 60 mg vitamin C, or 60 mg vitamin C alone daily for 12 weeks. Endothelial function in the brachial artery was assessed by flow-mediated vasodilation (FMD). FMD improved in both treatment groups (p effect on macrovascular endothelial function over and above that seen in the vitamin C alone group. However, Enzogenol did demonstrate additional favourable effects on protein oxidative damage and fibrinogen levels.

Involvement of systemic venous congestion in heart failure.

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Rubio Gracia, J; Sánchez Marteles, M; Pérez Calvo, J I

2017-04-01

Systemic venous congestion has gained significant importance in the interpretation of the pathophysiology of acute heart failure, especially in the development of renal function impairment during exacerbations. In this study, we review the concept, clinical characterisation and identification of venous congestion. We update current knowledge on its importance in the pathophysiology of acute heart failure and its involvement in the prognosis. We pay special attention to the relationship between abdominal congestion, the pulmonary interstitium as filtering membrane, inflammatory phenomena and renal function impairment in acute heart failure. Lastly, we review decongestion as a new therapeutic objective and the measures available for its assessment. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Prophylaxis of Venous Thrombosis.

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Goldhaber, Samuel Z.

2001-06-01

Mechanical measures such as graduated compression stockings and intermittent compression boots are available for venous thrombosis prophylaxis, but compliance may be limited. Plantar venous pneumatic compression devices have attained widespread acceptance by both patients and nurses because of their comfort and compact size, but their track record for efficacy is poor. Inferior vena cava filters prevent pulmonary embolism, but do not halt the thrombotic process or prevent venous thrombosis. Pharmacologic prophylaxis traditionally has relied upon minidose unfractionated heparin; however, re-examination is warranted in the face of increasingly ill and complex patients. My opinion is that small, fixed doses of once-daily low molecular weight heparin will eventually replace minidose unfractionated heparin as the standard pharmacologic prophylaxis regimen for most surgical and medical patients. Prolongation of prophylaxis after hospital discharge should receive increased emphasis. Most patients being transferred to a skilled nursing facility should receive venous thromboembolism prophylaxis. Similarly, most patients undergoing total hip or knee replacement should receive prolonged preventive regimens, with at least 1 month of anticoagulation. Despite advances, certain aspects of venous thrombosis prophylaxis remain problematic. First, a surprisingly high number of hospitalized patients develop venous thrombosis because of failed (rather than omitted) prophylaxis. Second, many patients in intensive care have a combination of peripheral vascular disease and active bleeding (usually gastrointestinal) that precludes mechanical or pharmacologic prophylaxis. Third, neurosurgical patients undergoing craniotomy for brain tumors suffer a high rate of venous thrombosis and major pulmonary embolism despite the routine use of combined mechanical and pharmacologic prophylaxis. My opinion is that these three areas, in addition to the hospital culture of prophylaxis, should receive

Lack of inhibitory effects of the anti-fibrotic drug imatinib on endothelial cell functions in vitro and in vivo.

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Venalis, Paulius; Maurer, Britta; Akhmetshina, Alfiya; Busch, Nicole; Dees, Clara; Stürzl, Michael; Zwerina, Jochen; Jüngel, Astrid; Gay, Steffen; Schett, Georg; Distler, Oliver; Distler, Jörg H W

2009-10-01

Systemic sclerosis (SSc) is a systemic autoimmune disease that is characterized by microangiopathy with progressive loss of capillaries and tissue fibrosis. Imatinib exerts potent anti-fibrotic effects and is currently evaluated in clinical trials. The aim of the present study was to exclude that the anti-fibrotic effects of imatinib are complicated by inhibitory effects on endothelial cell functions, which might augment vascular disease in SSc. Endothelial cells and mice were treated with pharmacologically relevant concentrations of imatinib. The expression of markers of vascular activation was assessed with real-time PCR. Proliferation was analysed with the cell counting experiments and the MTT assay. Apoptosis was quantified with caspase 3 assays, annexin V in vitro and with TUNEL staining in vivo. Migration was studied with scratch and transwell assays. Tube forming was investigated with the matrigel assay. Imatinib did not alter the expression of markers of vascular activation. Imatinib did not increase the percentage of annexin V positive cells or the activity of caspase 3. No reduction in proliferation or metabolic activity of endothelial cells was observed. Imatinib did not affect migration of endothelial cells and did not reduce the formation of capillary tubes. Consistent with the in vitro data, no difference in the number of apoptotic endothelial cells was observed in vivo in mice treated with imatinib. Imatinib does not inhibit activation, viability, proliferation, migration or tube forming of endothelial cells in vitro and in vivo. Thus, treatment with imatinib might not augment further endothelial cell damage in SSc.

Apoptosis of Endothelial Cells by 13-HPODE Contributes to Impairment of Endothelial Barrier Integrity

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Valerie E. Ryman

2016-01-01

Full Text Available Inflammation is an essential host response during bacterial infections such as bovine mastitis. Endothelial cells are critical for an appropriate inflammatory response and loss of vascular barrier integrity is implicated in the pathogenesis of Streptococcus uberis-induced mastitis. Previous studies suggested that accumulation of linoleic acid (LA oxygenation products derived from 15-lipoxygenase-1 (15-LOX-1 metabolism could regulate vascular functions. The initial LA derivative from the 15-LOX-1 pathway, 13-hydroperoxyoctadecadienoic acid (HPODE, can induce endothelial death, whereas the reduced hydroxyl product, 13-hydroxyoctadecadienoic acid (HODE, is abundantly produced during vascular activation. However, the relative contribution of specific LA-derived metabolites on impairment of mammary endothelial integrity is unknown. Our hypothesis was that S. uberis-induced LA-derived 15-LOX-1 oxygenation products impair mammary endothelial barrier integrity by apoptosis. Exposure of bovine mammary endothelial cells (BMEC to S. uberis did not increase 15-LOX-1 LA metabolism. However, S. uberis challenge of bovine monocytes demonstrated that monocytes may be a significant source of both 13-HPODE and 13-HODE during mastitis. Exposure of BMEC to 13-HPODE, but not 13-HODE, significantly reduced endothelial barrier integrity and increased apoptosis. Changing oxidant status by coexposure to an antioxidant during 13-HPODE treatment prevented adverse effects of 13-HPODE, including amelioration of apoptosis. A better understanding of how the oxidant status of the vascular microenvironment impacts endothelial barrier properties could lead to more efficacious treatments for S. uberis mastitis.

Flavonoid-rich dark chocolate improves endothelial function and increases plasma epicatechin concentrations in healthy adults.

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Engler, Mary B; Engler, Marguerite M; Chen, Chung Y; Malloy, Mary J; Browne, Amanda; Chiu, Elisa Y; Kwak, Ho-Kyung; Milbury, Paul; Paul, Steven M; Blumberg, Jeffrey; Mietus-Snyder, Michele L

2004-06-01

Dark chocolate derived from the plant (Theobroma cacao) is a rich source of flavonoids. Cardioprotective effects including antioxidant properties, inhibition of platelet activity, and activation of endothelial nitric oxide synthase have been ascribed to the cocoa flavonoids. To investigate the effects of flavonoid-rich dark chocolate on endothelial function, measures of oxidative stress, blood lipids, and blood pressure in healthy adult subjects. The study was a randomized, double-blind, placebo-controlled design conducted over a 2 week period in 21 healthy adult subjects. Subjects were randomly assigned to daily intake of high-flavonoid (213 mg procyanidins, 46 mg epicatechin) or low-flavonoid dark chocolate bars (46 g, 1.6 oz). High-flavonoid chocolate consumption improved endothelium-dependent flow-mediated dilation (FMD) of the brachial artery (mean change = 1.3 +/- 0.7%) as compared to low-flavonoid chocolate consumption (mean change = -0.96 +/- 0.5%) (p = 0.024). No significant differences were noted in the resistance to LDL oxidation, total antioxidant capacity, 8-isoprostanes, blood pressure, lipid parameters, body weight or body mass index (BMI) between the two groups. Plasma epicatechin concentrations were markedly increased at 2 weeks in the high-flavonoid group (204.4 +/- 18.5 nmol/L, p < or = 0.001) but not in the low-flavonoid group (17.5 +/- 9 nmol/L, p = 0.99). Flavonoid-rich dark chocolate improves endothelial function and is associated with an increase in plasma epicatechin concentrations in healthy adults. No changes in oxidative stress measures, lipid profiles, blood pressure, body weight or BMI were seen.

Pancreas Transplant Venous Thrombosis: Role of Endovascular Interventions for Graft Salvage

International Nuclear Information System (INIS)

Stockland, Andrew H.; Willingham, Darrin L.; Paz-Fumagalli, Ricardo; Grewal, Hani P.; McKinney, J. Mark; Hughes, Christopher B.; Walser, Eric M.

2009-01-01

Venous thrombosis of pancreas transplant allografts often leads to graft loss. We evaluated the efficacy of emergent endovascular techniques to salvage thrombosed pancreatic allografts in a series of six patients. Of the 76 pancreas transplants performed between 2002 and 2006, six patients were diagnosed with venous thrombosis on MRI between 2 and 28 days posttransplant (mean, 9 days). Five patients were systemic-enteric (donor portal vein anastomosis to recipient iliac vein) and one patient was portal-enteric (donor portal vein anastomosis to recipient superior mesenteric vein). Conventional venography confirmed the diagnosis of venous thrombosis in all patients. One patient was treated with catheter-directed venous thrombolysis and balloon thrombectomy. Another patient was treated with rheolytic thrombectomy alone. The remaining four patients were treated with a combination of these mechanical and thrombolytic techniques. Completion venography revealed >50% clot reduction and resumption of venous drainage in all patients. One patient required additional intervention 16 days later for recurrent thrombosis. Two patients required metal stent placement for anastomotic stenoses or kinks. One patient required pancreatectomy 36 h after attempted salvage secondary to a major hemorrhage and graft necrosis. Two patients recovered pancreatic function initially but lost graft function at 8 and 14 months, respectively, from severe chronic rejection. Patient survival was 100%, long-term graft survival was 50%, rethrombosis rate was 16.6%, and graft loss from rejection was 33%. In conclusion, early recognition and treatment of venous thrombosis after pancreas transplantation has acceptable morbidity and no mortality using short-term endovascular pharmacomechanical therapy.

A novel approach for assessing the progression of deep venous thrombosis by area of venous thrombus in ultrasonic elastography.

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Wang, Chao; Wang, Lei; Zhang, Yuhui; Chen, Ming

2014-04-01

Exact age determination of deep venous thrombosis (DVT) is important for an appropriate treatment. The purpose of this present study is to assess the age of acute DVT with the area of venous thrombi in elasticity imaging during the thrombosis procession. The thrombus area is obtained from a specially designed program. It was applied to clot specimens induced in human great saphenous (n = 15) at selected time points following the initiation of thrombosis. The relative mean proportion of blood clots was 50.01% ± 12.44% at day 1; 69.94% ± 8.19% at day 3; 81.93% ± 6.15% at day 6; and 92.37% ± 4.06% at day 9. The results indicated that the thrombus area increased significantly over time, while the normalized strain values inside the thrombus changed only a little. The pathological analyses also showed the same results. Therefore, we conclude that the area of venous thrombi in elasticity imaging may be a novel function for acute DVT staging.

Assessment of coagulation function and ultrasound features after reteplase and recombinant streptokinase thrombolysis of lower extremity deep venous thrombosis

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Wei Xiong

2016-07-01

Full Text Available Objective: To assess coagulation function and ultrasound features after reteplase and recombinant streptokinase thrombolysis of lower extremity deep venous thrombosis. Methods: A total of 78 cases of patients with lower extremity deep venous thrombosis who were treated in our hospital were selected as research subjects and divided into observation group 39 cases and control group 39 cases according to different treatment regimens. Control group received recombinant streptokinase thrombolysis, observation group received reteplase thrombolysis, and then the effect of the two thrombolytic ways was evaluated by color Doppler ultrasonography and circulating blood test. Results: Ultrasound showed that complete recanalization rate of thrombus of observation group after treatment was higher than that of control group; plasma PT, APTT and TT values of observation group after thrombolysis were higher than those of control group, FIB, D-D, NO, ET, E-selectin, P-selectin, Hcy, CRP, IL-6, IL-8 and TNF-毩 values were lower than those of control group, and WBC, Nc and Mc cell number were less than those of control group. Conclusion: Reteplase for thrombolysis of lower extremity deep venous thrombosis has more distinguished effect on dissolving thrombus as well as optimizing body’s coagulation, inflammatory system state and other aspects, and is a more ideal thrombolytic drug.

Endothelial function in young women with polycystic ovary syndrome (PCOS): Implications of body mass index (BMI) and insulin resistance.

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El-Kannishy, Ghada; Kamal, Shaheer; Mousa, Amany; Saleh, Omayma; Badrawy, Adel El; Farahaty, Reham El; Shokeir, Tarek

2010-01-01

Evidence regarding endothelial function in both obese and nonobese women with PCOS is contradictory. It is unknown whether obese women with PCOS carry an increased risk related to body mass index (BMI). To identify endothelial function and investigate its relationship to body mass index and insulin resistance in young women with PCOS. Twenty-two obese women with PCOS (BMI 35.2 ± 3.2) as well as fourteen lean women (BMI 22.8 ± 2.1)with PCOS were included in the study. Fasting serum insulin, blood glucose were estimated and HOMA and Quicki index were calculated. All patients were subjected to ultrasound recording of brachial artery diameter at rest and after reactive hyperemia (FMD) for assessment of endothelial function. Ten age matched healthy females with normal BMI were chosen as a control group. There were higher basal insulin levels with lower Quicki index and higher HOMA index in women with PCOS than normal group, but the differences were significant only between obese PCOS subgroup and control. On the other hand, FMD was significantly and equally decreased in both groups of women with PCOS, compared with control subjects (3.7 ± 3.2% in the nonobese subgroup and 3.5 ± 2.8% in the obese one vs. 10.6 ± 4.1% in control subjects, P, 0.001). FMD was not correlated with BMI nor insulin resistance indices. Endothelial dysfunction is already present in young women with PCOS. In this patient group, it cannot be attributed to insulin resistance or obesity. © 2010 Asian Oceanian Association for the Study of Obesity . Published by Elsevier Ltd. All rights reserved.

Cigarette smoke extract counteracts atheroprotective effects of high laminar flow on endothelial function

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Sindy Giebe

2017-08-01

Full Text Available Tobacco smoking and hemodynamic forces are key stimuli in the development of endothelial dysfunction and atherosclerosis. High laminar flow has an atheroprotective effect on the endothelium and leads to a reduced response of endothelial cells to cardiovascular risk factors compared to regions with disturbed or low laminar flow. We hypothesize that the atheroprotective effect of high laminar flow could delay the development of endothelial dysfunction caused by cigarette smoking. Primary human endothelial cells were stimulated with increasing dosages of aqueous cigarette smoke extract (CSEaq. CSEaq reduced cell viability in a dose-dependent manner. The main mediator of cellular adaption to oxidative stress, nuclear factor erythroid 2-related factor 2 (NRF2 and its target genes heme oxygenase (decycling 1 (HMOX1 or NAD(PH quinone dehydrogenase 1 (NQO1 were strongly increased by CSEaq in a dose-dependent manner. High laminar flow induced elongation of endothelial cells in the direction of flow, activated the AKT/eNOS pathway, increased eNOS expression, phosphorylation and NO release. These increases were inhibited by CSEaq. Pro-inflammatory adhesion molecules intercellular adhesion molecule-1 (ICAM1, vascular cell adhesion molecule-1 (VCAM1, selectin E (SELE and chemokine (C-C motif ligand 2 (CCL2/MCP-1 were increased by CSEaq. Low laminar flow induced VCAM1 and SELE compared to high laminar flow. High laminar flow improved endothelial wound healing. This protective effect was inhibited by CSEaq in a dose-dependent manner through the AKT/eNOS pathway. Low as well as high laminar flow decreased adhesion of monocytes to endothelial cells. Whereas, monocyte adhesion was increased by CSEaq under low laminar flow, this was not evident under high laminar flow.This study shows the activation of major atherosclerotic key parameters by CSEaq. Within this process, high laminar flow is likely to reduce the harmful effects of CSEaq to a certain degree. The

Alcohol consumption negates estrogen-mediated myocardial repair in ovariectomized mice by inhibiting endothelial progenitor cell mobilization and function.

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Mackie, Alexander R; Krishnamurthy, Prasanna; Verma, Suresh K; Thorne, Tina; Ramirez, Veronica; Qin, Gangjian; Abramova, Tatiana; Hamada, Hiromichi; Losordo, Douglas W; Kishore, Raj

2013-06-21

We have shown previously that estrogen (estradiol, E2) supplementation enhances voluntary alcohol consumption in ovariectomized female rodents and that increased alcohol consumption impairs ischemic hind limb vascular repair. However, the effect of E2-induced alcohol consumption on post-infarct myocardial repair and on the phenotypic/functional properties of endothelial progenitor cells (EPCs) is not known. Additionally, the molecular signaling of alcohol-estrogen interactions remains to be elucidated. This study examined the effect of E2-induced increases in ethanol consumption on post-infarct myocardial function/repair. Ovariectomized female mice, implanted with 17β-E2 or placebo pellets were given access to alcohol for 6 weeks and subjected to acute myocardial infarction. Left ventricular functions were consistently depressed in mice consuming ethanol compared with those receiving only E2. Alcohol-consuming mice also displayed significantly increased infarct size and reduced capillary density. Ethanol consumption also reduced E2-induced mobilization and homing of EPCs to injured myocardium compared with the E2-alone group. In vitro, exposure of EPCs to ethanol suppressed E2-induced proliferation, survival, and migration and markedly altered E2-induced estrogen receptor-dependent cell survival signaling and gene expression. Furthermore, ethanol-mediated suppression of EPC biology was endothelial nitric oxide synthase-dependent because endothelial nitric oxide synthase-null mice displayed an exaggerated response to post-acute myocardial infarction left ventricular functions. These data suggest that E2 modulation of alcohol consumption, and the ensuing EPC dysfunction, may negatively compete with the beneficial effects of estrogen on post-infarct myocardial repair.

Fingertip replantations: importance of venous anastomosis and the clinical results.

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Hasuo, Takaaki; Nishi, Genzaburo; Tsuchiya, Daiji; Otsuka, Takanobu

2009-01-01

Overall survival rate for 143 digits with complete amputation of the distal phalanx was 78%. Replanted digits that underwent venous anastomosis showed a very high survival rate of 93%. Loss of the distal interphalangeal joint function in subzone IV was significantly inferior to that in subzones II and III. Protective sensation was achieved in 96% of replanted digits. Sensory recovery in the absence of nerve repair was significantly worse for avulsion injury than for crush injury. Nail deformity tended to be increased for replanted digits in subzone III or with crush-type injury. Successful venous anastomosis appears to offer the best way to promote survival of replanted digits. If venous anastomosis is infeasible, a replanted digit can survive with any methods for venous drainage in subzones II and III, but does not survive in subzone IV. To minimise nail deformity, repair of the germinal matrix is necessary.

Granulocyte colony-stimulating factor mobilizes functional endothelial progenitor cells in patients with coronary artery disease.

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Powell, Tiffany M; Paul, Jonathan D; Hill, Jonathan M; Thompson, Michael; Benjamin, Moshe; Rodrigo, Maria; McCoy, J Philip; Read, Elizabeth J; Khuu, Hanh M; Leitman, Susan F; Finkel, Toren; Cannon, Richard O

2005-02-01

Endothelial progenitor cells (EPCs) that may repair vascular injury are reduced in patients with coronary artery disease (CAD). We reasoned that EPC number and function may be increased by granulocyte colony-stimulating factor (G-CSF) used to mobilize hematopoietic progenitor cells in healthy donors. Sixteen CAD patients had reduced CD34(+)/CD133(+) (0.0224+/-0.0063% versus 0.121+/-0.038% mononuclear cells [MNCs], P<0.01) and CD133(+)/VEGFR-2(+) cells, consistent with EPC phenotype (0.00033+/-0.00015% versus 0.0017+/-0.0006% MNCs, P<0.01), compared with 7 healthy controls. Patients also had fewer clusters of cells in culture, with out-growth consistent with mature endothelial phenotype (2+/-1/well) compared with 16 healthy subjects at high risk (13+/-4/well, P<0.05) or 14 at low risk (22+/-3/well, P<0.001) for CAD. G-CSF 10 microg/kg per day for 5 days increased CD34(+)/CD133(+) cells from 0.5+/-0.2/microL to 59.5+/-10.6/microL and CD133(+)/ VEGFR-2(+) cells from 0.007+/-0.004/microL to 1.9+/-0.6/microL (both P<0.001). Also increased were CD133(+) cells that coexpressed the homing receptor CXCR4 (30.4+/-8.3/microL, P<0.05). Endothelial cell-forming clusters in 10 patients increased to 27+/-9/well after treatment (P<0.05), with a decline to 9+/-4/well at 2 weeks (P=0.06). Despite reduced EPCs compared with healthy controls, patients with CAD respond to G-CSF with increases in EPC number and homing receptor expression in the circulation and endothelial out-growth in culture. Endothelial progenitor cells (EPCs) are reduced in coronary artery disease. Granulocyte colony-stimulating factor (CSF) administered to patients increased: (1) CD133+/VEGFR-2+ cells consistent with EPC phenotype; (2) CD133+ cells coexpressing the chemokine receptor CXCR4, important for homing of EPCs to ischemic tissue; and (3) endothelial cell-forming clusters in culture. Whether EPCs mobilized into the circulation will be useful for the purpose of initiating vascular growth and myocyte repair

Long noncoding RNA LISPR1 is required for S1P signaling and endothelial cell function.

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Josipovic, Ivana; Pflüger, Beatrice; Fork, Christian; Vasconez, Andrea E; Oo, James A; Hitzel, Juliane; Seredinski, Sandra; Gamen, Elisabetta; Heringdorf, Dagmar Meyer Zu; Chen, Wei; Looso, Mario; Pullamsetti, Soni Savai; Brandes, Ralf P; Leisegang, Matthias S

2018-03-01

Sphingosine-1-Phosphate (S1P) is a potent signaling lipid. The effects of S1P are mediated by the five S1P receptors (S1PR). In the endothelium S1PR1 is the predominant receptor and thus S1PR1 abundance limits S1P signaling. Recently, lncRNAs were identified as a novel class of molecules regulating gene expression. Interestingly, the lncRNA NONHSAT004848 (LISPR1, Long intergenic noncoding RNA antisense to S1PR1), is closely positioned to the S1P1 receptors gene and in part shares its promoter region. We hypothesize that LISPR1 controls endothelial S1PR1 expression and thus S1P-induced signaling in endothelial cells. In vitro transcription and translation as well as coding potential assessment showed that LISPR1 is indeed noncoding. LISPR1 was localized in both cytoplasm and nucleus and harbored a PolyA tail at the 3'end. In human umbilical vein endothelial cells, as well as human lung tissue, qRT-PCR and RNA-Seq revealed high expression of LISPR1. S1PR1 and LISPR1 were downregulated in human pulmonary diseases such as COPD. LISPR1 but also S1PR1 were induced by inflammation, shear stress and statins. Knockdown of LISPR1 attenuated endothelial S1P-induced migration and spheroid outgrowth of endothelial cells. LISPR1 knockdown decreased S1PR1 expression, which was paralleled by an increase of the binding of the transcriptional repressor ZNF354C to the S1PR1 promoter and a reduction of the recruitment of RNA Polymerase II to the S1PR1 5'end. This resulted in attenuated S1PR1 expression and attenuated S1P downstream signaling. Collectively, the disease relevant lncRNA LISPR1 acts as a novel regulatory unit important for S1PR1 expression and endothelial cell function. Copyright © 2018 Elsevier Ltd. All rights reserved.

Dietary saturated and unsaturated fats as determinants of blood pressure and vascular function.

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Hall, Wendy L

2009-06-01

The amount and type of dietary fat have long been associated with the risk of CVD. Arterial stiffness and endothelial dysfunction are important risk factors in the aetiology of CHD. A range of methods exists to assess vascular function that may be used in nutritional science, including clinic and ambulatory blood pressure monitoring, pulse wave analysis, pulse wave velocity, flow-mediated dilatation and venous occlusion plethysmography. The present review focuses on the quantity and type of dietary fat and effects on blood pressure, arterial compliance and endothelial function. Concerning fat quantity, the amount of dietary fat consumed habitually appears to have little influence on vascular function independent of fatty acid composition, although single high-fat meals postprandially impair endothelial function compared with low-fat meals. The mechanism is related to increased circulating lipoproteins and NEFA which may induce pro-inflammatory pathways and increase oxidative stress. Regarding the type of fat, cross-sectional data suggest that saturated fat adversely affects vascular function whereas polyunsaturated fat (mainly linoleic acid (18 : 2n-6) and n-3 PUFA) are beneficial. EPA (20 : 5n-3) and DHA (22 : 6n-3) can reduce blood pressure, improve arterial compliance in type 2 diabetics and dyslipidaemics, and augment endothelium-dependent vasodilation. The mechanisms for this vascular protection, and the nature of the separate physiological effects induced by EPA and DHA, are priorities for future research. Since good-quality observational or interventional data on dietary fatty acid composition and vascular function are scarce, no further recommendations can be suggested in addition to current guidelines at the present time.

The effect of diet and exercise on markers of endothelial function in overweight and obese women with polycystic ovary syndrome.

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Thomson, R L; Brinkworth, G D; Noakes, M; Clifton, P M; Norman, R J; Buckley, J D

2012-07-01

Women with polycystic ovary syndrome (PCOS) present with vascular abnormalities, including elevated markers of endothelial dysfunction. There is limited evidence for the effect of lifestyle modification and weight loss on these markers. The aim of this study was to determine if 20 weeks of a high-protein energy-restricted diet with or without exercise in women with PCOS could improve endothelial function. This is a secondary analysis of a subset of 50 overweight/obese women with PCOS (age: 30.3 ± 6.3 years; BMI: 36.5 ± 5.7 kg/m(2)) from a previous study. Participants were randomly assigned by computer generation to one of three 20-week interventions: diet only (DO; n = 14, ≈ 6000 kJ/day), diet and aerobic exercise (DA; n = 16, ≈ 6000 kJ/day and five walking sessions/week) and diet and combined aerobic-resistance exercise (DC; n = 20, ≈ 6000 kJ/day, three walking and two strength sessions/week). At Weeks 0 and 20, weight, markers of endothelial function [vascular cell adhesion molecule-1 (sVCAM-1), inter-cellular adhesion molecule-1 (sICAM-1), plasminogen activator inhibitor-1 (PAI-1) and asymmetric dimethylarginine (ADMA)], insulin resistance and hormonal profile were assessed. All three treatments resulted in significant weight loss (DO 7.9 ± 1.2%, DA 11.0 ± 1.6%, DC 8.8 ± 1.1; P Exercise training provided no additional benefit to following a high-protein, hypocaloric diet on markers of endothelial function in overweight/obese women with PCOS.

GPER Mediates Functional Endothelial Aging in Renal Arteries.

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Meyer, Matthias R; Rosemann, Thomas; Barton, Matthias; Prossnitz, Eric R

2017-01-01

Aging is associated with impaired renal artery function, which is partly characterized by arterial stiffening and a reduced vasodilatory capacity due to excessive generation of reactive oxygen species by NADPH oxidases (Nox). The abundance and activity of Nox depends on basal activity of the heptahelical transmembrane receptor GPER; however, whether GPER contributes to age-dependent functional changes in renal arteries is unknown. This study investigated the effect of aging and Nox activity on renal artery tone in wild-type and GPER-deficient (Gper-/-) mice (4 and 24 months old). In wild-type mice, aging markedly impaired endothelium-dependent, nitric oxide (NO)-mediated relaxations to acetylcholine, which were largely preserved in renal arteries of aged Gper-/- mice. The Nox inhibitor gp91ds-tat abolished this difference by greatly enhancing relaxations in wild-type mice, while having no effect in Gper-/- mice. Contractions to angiotensin II and phenylephrine in wild-type mice were partly sensitive to gp91ds-tat but unaffected by aging. Again, deletion of GPER abolished effects of Nox inhibition on contractile responses. In conclusion, basal activity of GPER is required for the age-dependent impairment of endothelium-dependent, NO-mediated relaxation in the renal artery. Restoration of relaxation by a Nox inhibitor in aged wild-type but not Gper-/- mice strongly supports a role for Nox-derived reactive oxygen species as the underlying cause. Pharmacological blockers of GPER signaling may thus be suitable to inhibit functional endothelial aging of renal arteries by reducing Nox-derived oxidative stress and, possibly, the associated age-dependent deterioration of kidney function. © 2017 S. Karger AG, Basel.

Dehydroepiandrosterone substitution in female adrenal failure: no impact on endothelial function and cardiovascular parameters despite normalization of androgen status

DEFF Research Database (Denmark)

Christiansen, Jens Juel; Andersen, Niels Holmark; Sørensen, Keld E

2007-01-01

because of skin side effects and anxiety, respectively. All patients had low circulating androgens baseline and normal range androgens during DHEA treatment. We examined patients with noninvasive endothelial cell function, magnetic resonance imaging (MRI)-based cardiac output, echocardiography, ambulatory...... 24-h blood pressure and maximal oxygen consumption. RESULTS: DHEA treatment normalized androgen status to levels seen in healthy women. DHEA and placebo treatment had no effect on echocardiographic parameters of myocardial dimensions or systolic and diastolic function, noninvasive endothelial cell...... in vascular endothelium has been described and in vitro studies have shown involvement of DHEA in NO dependent pathways. AIM: To evaluate effects of DHEA substitution on cardiovascular parameters. DESIGN: Six months randomized, double-blind, placebo-controlled crossover study. Treatment consisted of DHEA 50...

Endothelial arginine resynthesis contributes to the maintenance of vasomotor function in male diabetic mice.

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Ramesh Chennupati

Full Text Available Argininosuccinate synthetase (ASS is essential for recycling L-citrulline, the by-product of NO synthase (NOS, to the NOS substrate L-arginine. Here, we assessed whether disturbed arginine resynthesis modulates endothelium-dependent vasodilatation in normal and diabetic male mice.Endothelium-selective Ass-deficient mice (Assfl/fl/Tie2Cretg/- = Ass-KOTie2 were generated by crossing Assfl/fl mice ( = control with Tie2Cre mice. Gene ablation in endothelial cells was confirmed by immunohistochemistry. Blood pressure (MAP was recorded in 34-week-old male mice. Vasomotor responses were studied in isolated saphenous arteries of 12- and 34-week-old Ass-KOTie2 and control animals. At the age of 10 weeks, diabetes was induced in control and Ass-KOTie2 mice by streptozotocin injections. Vasomotor responses of diabetic animals were studied 10 weeks later. MAP was similar in control and Ass-KOTie2 mice. Depletion of circulating L-arginine by arginase 1 infusion or inhibition of NOS activity with L-NAME resulted in an increased MAP (10 and 30 mmHg, respectively in control and Ass-KOTie2 mice. Optimal arterial diameter, contractile responses to phenylephrine, and relaxing responses to acetylcholine and sodium nitroprusside were similar in healthy control and Ass-KOTie2 mice. However, in diabetic Ass-KOTie2 mice, relaxation responses to acetylcholine and endothelium-derived NO (EDNO were significantly reduced when compared to diabetic control mice.Absence of endothelial citrulline recycling to arginine did not affect blood pressure and systemic arterial vasomotor responses in healthy mice. EDNO-mediated vasodilatation was significantly more impaired in diabetic Ass-KOTie2 than in control mice demonstrating that endothelial arginine recycling becomes a limiting endothelial function in diabetes.

Complications of central venous stenosis due to permanent central venous catheters in children on hemodialysis.

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Rinat, Choni; Ben-Shalom, Efrat; Becker-Cohen, Rachel; Feinstein, Sofia; Frishberg, Yaacov

2014-11-01

Central venous catheters are frequently used as access for hemodialysis (HD) in children. One of the known complications is central venous stenosis. Although this complication is not rare, it is often asymptomatic and therefore unacknowledged. Superior vena cava (SVC) stenosis is obviously suspected in the presence of upper body edema, but several other signs and symptoms are often unrecognized as being part of this syndrome. We describe four patients with various manifestations of central venous stenosis and SVC syndrome. These sometimes life- or organ-threatening conditions include obstructive sleep apnea, unresolving stridor, increased intracranial pressure, increased intraocular pressure, right-sided pleural effusion, protein-losing enteropathy and lymphadenopathy. The temporal relationship of these complications associated with the use of central venous catheters and documentation of venous stenosis, together with their resolution after alleviation of high venous pressure, points to a causal role. We suggest pathophysiological mechanisms for the formation of each of these complications. In patients with occlusion of the SVC, various unexpected clinical entities can be caused by high central venous pressure. As often the etiology is not obvious, a high index of suspicion is needed as in some cases prompt alleviation of the high pressure is mandatory.

Ultrastructural investigations for reducing endothelial cell damage of vein grafts during CABG-operation and practical consequences.

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Hickethier, T; Dämmrich, J; Silber, R E; Finster, S; Elert, O

1999-02-01

In the present study the influence of different storage solutions on endothelial integrity or damage was investigated with direct methods particularly with transmission electron microscopy (TEM), scanning electron microscopy (SEM) and immunohistochemistry. Saphenous vein segments of 10 cm in length were taken surgically from 6 male CABG-patients (aged 60-70) under standardized conditions. Each vein segment was cut into rings, which were incubated at room temperature for 45 minutes in different storage solutions, particularly in 0.9% sodium chloride solution and in buffered solution (M 199) with 5% human serum albumin respectively. Then, the vein segments were fixed in 3.5% glutaraldehyde and prepared for scanning and transmission electron microscopy to evaluate the endothelial damage. In addition, immunohistochemical staining (CD34, PECAM and Factor VIII) was performed. When using 0.9% sodium chloride solution, the SEM-examination revealed that 55% of the cell population was destroyed. In comparison to these findings only 26% of the endothelial cell population was damaged when the venous segment was stored in buffered solution with 5% albumin (p<0.01). In immunohistochemistry (CD34, PECAM, Factor VIII) these findings were supported. This study demonstrates the importance of storage solutions in regard to endothelial integrity. For best preservation of endothelium it is necessary to modify conventional storage methods. So, storage in buffered solution with albumin has shown much better endothelial cell preservation compared with physiological saline which might reduce the obliteration rate of CABG in future.

Ionizing radiation activates vascular endothelial growth factor-A transcription in human umbilical vein endothelial cells

Energy Technology Data Exchange (ETDEWEB)

Lee, Hyounji; Kim, Kwang Seok; Jeong, Jae Hoon; Lim, Young Bin [Radiation Cancer Biology Team, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

2016-12-15

Vascular endothelial growth factor (VEGF) is an essential paracrine factor for developmental and pathological angiogenesis. VEGF also exerts its effects in an autocrine manner in VEGF-producing cells. For instance, autocrine VEGF signaling occurs in tumor cells and contributes to key aspects of tumorigenesis, such as in the function of cancer stem cells and tumor initiation, which are independent of angiogenesis. In addition to tumors cells, non-transformed cells also express VEGF. For example, a VEGF dependent intracellular autocrine mechanism is crucial for the survival of hematopoietic stem cells and hematopoiesis. Stereotactic body radiation therapy (SBRT) is a novel treatment modality for early primary cancer and oligometastatic disease. SBRT delivers high-dose hypofractionated radiation, such as 20-60 Gy, to tumors in a single fraction or 2-5 fractions. As VEGF is a critical regulator of functional integrity and viability of vascular endothelial cells, we examined whether high-dose irradiation alters VEGF signaling by measuring the expression levels of VEGFA transcript. It is generally believed that endothelial cells do not produce VEGF in response to radiation. In present study, however, we provide the first demonstration of transcriptional regulation of VEGFA in human vascular endothelial cells by IR treatment. Irradiation with doses higher than 10 Gy in a single exposure triggers up-regulation of VEGFA transcription within 2 hours in HUVECs, whereas irradiation with 10 Gy does not alter VEGFA levels. Our data have shown that high-dose irradiation triggers immediate transactivation of VEGFA in human vascular endothelial cells.

Role of protein kinase C in regulation of Na+- and K +-dependent ATPase activity and pump function in corneal endothelial cells.

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Hatou, Shin; Yamada, Masakazu; Mochizuki, Hiroshi; Nishida, Teruo

2009-05-01

Na+- and K+-dependent ATPase (Na,K-ATPase) plays an important role in the pump function of the corneal endothelium. We investigated the possible role of protein kinase C (PKC) in regulation of Na,K-ATPase activity and pump function in corneal endothelial cells. Confluent monolayers of mouse corneal endothelial cells were exposed to phorbol 12,13-dibutyrate (PDBu) to induce activation of PKC. ATPase activity of the cells was evaluated by using ammonium molybdate in spectrophotometric measurement of phosphate released from ATP, with Na,K-ATPase activity being defined as the portion of total ATPase activity sensitive to ouabain. Pump function of the cells was measured with a Ussing chamber, with the pump function attributable to Na,K-ATPase activity being defined as the portion of the total short-circuit current sensitive to ouabain. PDBu (10(-7) M) increased the Na,K-ATPase activity and pump function of the cultured cells. These effects of PDBu were potentiated by the cyclooxygenase inhibitor indomethacin and the cytochrome P(450) inhibitor resorufin and were blocked by okadaic acid, an inhibitor of protein phosphatases 1 and 2A. Our results suggest that PKC bidirectionally regulates Na,K-ATPase activity in mouse corneal endothelial cells: it inhibits Na,K-ATPase activity in a cyclooxygenase- and cytochrome P(450)-dependent manner, whereas it stimulates such activity by activating protein phosphatases 1 or 2A.

Femoral venous oxygen saturation is no surrogate for central venous oxygen saturation

NARCIS (Netherlands)

van Beest, Paul A.; van der Schors, Alice; Liefers, Henriëtte; Coenen, Ludo G. J.; Braam, Richard L.; Habib, Najib; Braber, Annemarije; Scheeren, Thomas W. L.; Kuiper, Michaël A.; Spronk, Peter E.

2012-01-01

Objective: The purpose of our study was to determine if central venous oxygen saturation and femoral venous oxygen saturation can be used interchangeably during surgery and in critically ill patients. Design: Prospective observational controlled study. Setting: Nonacademic university-affiliated

Effect of Uric Acid-Lowering Agents on Endothelial Function: A Randomized, Double-Blind, Placebo-Controlled Trial.

Science.gov (United States)

Borgi, Lea; McMullan, Ciaran; Wohlhueter, Ann; Curhan, Gary C; Fisher, Naomi D; Forman, John P

2017-02-01

Higher levels of serum uric acid are independently associated with endothelial dysfunction, a mechanism for incident hypertension. Overweight/obese individuals are more prone to endothelial dysfunction than their lean counterparts. However, the effect of lowering serum uric acid on endothelial dysfunction in these individuals has not been examined thoroughly. In this randomized, double-blind, placebo-controlled trial of nonhypertensive, overweight, or obese individuals with higher serum uric acid (body mass index ≥25 kg/m 2 and serum uric acid ≥5.0 mg/dL), we assigned subjects to probenecid (500-1000 mg/d), allopurinol (300-600 mg/d), or matching placebo. The primary outcome was endothelium-dependent vasodilation measured by brachial artery ultrasound at baseline and 8 weeks. By the end of the trial, 47, 49, and 53 participants had been allocated to receive probenecid, allopurinol, and placebo, respectively. Mean serum uric acid levels significantly decreased in the probenecid (from 6.1 to 3.5 mg/dL) and allopurinol groups (from 6.1 to 2.9 mg/dL) but not in the placebo group (6.1 to 5.6 mg/dL). None of the interventions produced any significant change in endothelium-dependent vasodilation (probenecid, 7.4±5.1% at baseline and 8.3±5.1% at 8 weeks; allopurinol, 7.6±6.0% at baseline and 6.2±4.8% at 8 weeks; and placebo, 6.5±3.8% at baseline and 7.1±4.9% at 8 weeks). In this randomized, double-blind, placebo-controlled trial, uric acid lowering did not affect endothelial function in overweight or obese nonhypertensive individuals. These data do not support the hypothesis that uric acid is causally related to endothelial dysfunction, a potential mechanism for development of hypertension. © 2016 American Heart Association, Inc.

Effect of Yixinkangtai Capsule combined with diltiazem on endothelial function, blood viscosity and lipid metabolism in patients with unstable angina pectoris

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Yu-Feng Yuan

2017-10-01

Full Text Available Objective: To discuss the effect of Yixinkangtai Capsule combined with diltiazem on endothelial function, blood viscosity and lipid metabolism in patients with unstable angina pectoris. Methods: A total of 150 patients with unstable angina pectoris who were treated in the hospital between February 2014 and February 2017 were divided into the control group (n=75 and the research group (n=75 according to the random number table method. Control group received clinical conventional therapy, research group received Yixinkangtai Capsule combined with diltiazem therapy on the basis of conventional therapy, and both groups received 3 months of treatment. Differences in endothelial function, blood viscosity and lipid metabolism were compared between the two groups of patients before and after treatment. Results: Before treatment, the differences in serum levels of endothelial function indexes, blood viscosity indexes and lipid metabolism indexes were not statistically significant between the two groups. After 3 months of treatment, serum NO level of research group was higher than that of control group while ET-1 level was lower than that of control group; serum blood viscosity index TXB2 content of research group was lower than that of control group while PGI2 content was higher than that of control group; serum lipid metabolism indexes TG, TC and LDL-C contents of research group were lower than those of control group while HDL-C content was higher than that of control group. Conclusion: Yixinkangtai Capsule combined with diltiazem therapy can effectively optimize the endothelial function, reduce the blood viscosity and balance the lipid metabolism in patients with unstable angina pectoris.

Red meat intake, insulin resistance, and markers of endothelial function among Iranian women.

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Barak, Farzaneh; Falahi, Ebrahim; Keshteli, Ammar Hassanzadeh; Yazdannik, Ahmadreza; Saneei, Parvane; Esmaillzadeh, Ahmad

2015-02-01

Few data, with conflicting findings, are available linking red meat consumption to indicators of insulin resistance and endothelial dysfunction. This study aimed to investigate the association of red meat consumption with insulin resistance and endothelial dysfunction among a sample of female nurses in Isfahan, Iran. This cross-sectional study was carried out among 420 female nurses who were selected by a multistage cluster random sampling method. Usual dietary intakes were assessed using a validated food frequency questionnaire. Red meat intake was calculated by summing up the consumption of all kinds of red meat in foods and processed meat in sausages and fast foods. To measure serum concentrations of adhesion molecules and glycemic indexes, a fasting blood sample was taken. After adjustment for potential confounders, high red meat intake was significantly associated with higher fasting plasma glucose, homeostasis model assessment of insulin resistance, and lower quantitative insulin sensitivity check index. Although high red meat intake was significantly associated with higher serum insulin levels and lower homeostasis model assessment of beta-cell function in the crude model, after controlling for BMI, the association was no longer significant. Red meat consumption was associated with high concentrations of E-selectin, soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble intercellular adhesion molecule-1 (sICAM-1) after adjustment for different potential confounders. We found that increased red meat intake was associated with high concentrations of plasma endothelial dysfunction biomarkers and abnormal glucose homeostasis among Iranian women. Prospective studies are required to confirm these findings. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Peripheral Venous Access Ports: Outcomes Analysis in 109 Patients

International Nuclear Information System (INIS)

Bodner, Leonard J.; Nosher, John L.; Patel, Kaushik M.; Siegel, Randall L.; Biswal, Rajiv; Gribbin, Christopher E.; Tokarz, Robert

2000-01-01

Purpose: To perform a retrospective outcomes analysis of central venous catheters with peripheral venous access ports, with comparison to published data.Methods: One hundred and twelve central venous catheters with peripherally placed access ports were placed under sonographic guidance in 109 patients over a 4-year period. Ports were placed for the administration of chemotherapy, hyperalimentation, long-term antibiotic therapy, gamma-globulin therapy, and frequent blood sampling. A vein in the upper arm was accessed in each case and the catheter was passed to the superior vena cava or right atrium. Povidone iodine skin preparation was used in the first 65 port insertions. A combination of Iodophor solution and povidone iodine solution was used in the last 47 port insertions. Forty patients received low-dose (1 mg) warfarin sodium beginning the day after port insertion. Three patients received higher doses of warfarin sodium for preexistent venous thrombosis. Catheter performance and complications were assessed and compared with published data.Results: Access into the basilic or brachial veins was obtained in all cases. Ports remained functional for a total of 28,936 patient days. The port functioned in 50% of patients until completion of therapy, or the patient's expiration. Ports were removed prior to completion of therapy in 18% of patients. Eleven patients (9.9% of ports placed) suffered an infectious complication (0.38 per thousand catheter-days)-in nine, at the port implantation site, in two along the catheter. In all 11 instances the port was removed. Port pocket infection in the early postoperative period occurred in three patients (4.7%) receiving a Betadine prep vs two patients (4.2%) receiving a standard O.R. prep. This difference was not statistically significant (p = 0.9). Venous thrombosis occurred in three patients (6.8%) receiving warfarin sodium and in two patients (3%) not receiving warfarin sodium. This difference was not statistically significant

Endothelial dysfunction in metabolic and vascular disorders.

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Polovina, Marija M; Potpara, Tatjana S

2014-03-01

Vascular endothelium has important regulatory functions in the cardiovascular system and a pivotal role in the maintenance of vascular health and metabolic homeostasis. It has long been recognized that endothelial dysfunction participates in the pathogenesis of atherosclerosis from early, preclinical lesions to advanced, thrombotic complications. In addition, endothelial dysfunction has been recently implicated in the development of insulin resistance and type 2 diabetes mellitus (T2DM). Considering that states of insulin resistance (eg, metabolic syndrome, impaired fasting glucose, impaired glucose tolerance, and T2DM) represent the most prevalent metabolic disorders and risk factors for atherosclerosis, it is of considerable scientific and clinical interest that both metabolic and vascular disorders have endothelial dysfunction as a common background. Importantly, endothelial dysfunction has been associated with adverse outcomes in patients with established cardiovascular disease, and a growing body of evidence indicates that endothelial dysfunction also imparts adverse prognosis in states of insulin resistance. In this review, we discuss the association of insulin resistance and T2DM with endothelial dysfunction and vascular disease, with a focus on the underlying mechanisms and prognostic implications of the endothelial dysfunction in metabolic and vascular disorders. We also address current therapeutic strategies for the improvement of endothelial dysfunction.

Femoral venous oxygen saturation is no surrogate for central venous oxygen saturation

NARCIS (Netherlands)

van Beest, Paul A.; van der Schors, Alice; Liefers, Henriette; Coenen, Ludo G. J.; Braam, Richard L.; Habib, Najib; Braber, Annemarije; Scheeren, Thomas W. L.; Kuiper, Michael A.; Spronk, Peter E.

2012-01-01

Objective:  The purpose of our study was to determine if central venous oxygen saturation and femoral venous oxygen saturation can be used interchangeably during surgery and in critically ill patients. Design:  Prospective observational controlled study. Setting:  Nonacademic university-affiliated

Increased endothelial cell-leukocyte interaction in murine schistosomiasis: possible priming of endothelial cells by the disease.

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Suellen D S Oliveira

Full Text Available BACKGROUND AND AIMS: Schistosomiasis is an intravascular parasitic disease associated with inflammation. Endothelial cells control leukocyte transmigration and vascular permeability being modulated by pro-inflammatory mediators. Recent data have shown that endothelial cells primed in vivo in the course of a disease keep the information in culture. Herein, we evaluated the impact of schistosomiasis on endothelial cell-regulated events in vivo and in vitro. METHODOLOGY AND PRINCIPAL FINDINGS: The experimental groups consisted of Schistosoma mansoni-infected and age-matched control mice. In vivo infection caused a marked influx of leukocytes and an increased protein leakage in the peritoneal cavity, characterizing an inflamed vascular and cellular profile. In vitro leukocyte-mesenteric endothelial cell adhesion was higher in cultured cells from infected mice as compared to controls, either in the basal condition or after treatment with the pro-inflammatory cytokine tumor necrosis factor (TNF. Nitric oxide (NO donation reduced leukocyte adhesion to endothelial cells from control and infected groups; however, in the later group the effect was more pronounced, probably due to a reduced NO production. Inhibition of control endothelial NO synthase (eNOS increased leukocyte adhesion to a level similar to the one observed in the infected group. Besides, the adhesion of control leukocytes to endothelial cells from infected animals is similar to the result of infected animals, confirming that schistosomiasis alters endothelial cells function. Furthermore, NO production as well as the expression of eNOS were reduced in cultured endothelial cells from infected animals. On the other hand, the expression of its repressor protein, namely caveolin-1, was similar in both control and infected groups. CONCLUSION/SIGNIFICANCE: Schistosomiasis increases vascular permeability and endothelial cell-leukocyte interaction in vivo and in vitro. These effects are partially

Effects of abdominal pressure on venous return: abdominal vascular zone conditions.

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Takata, M; Wise, R A; Robotham, J L

1990-12-01

The effects of changes in abdominal pressure (Pab) on inferior vena cava (IVC) venous return were analyzed using a model of the IVC circulation based on a concept of abdominal vascular zone conditions analogous to pulmonary vascular zone conditions. We hypothesized that an increase in Pab would increase IVC venous return when the IVC pressure at the level of the diaphragm (Pivc) exceeds the sum of Pab and the critical closing transmural pressure (Pc), i.e., zone 3 conditions, but reduce IVC venous return when Pivc is below the sum of Pab and Pc, i.e., zone 2 conditions. The validity of the model was tested in 12 canine experiments with an open-chest IVC bypass. An increase in Pab produced by phrenic stimulation increased the IVC venous return when Pivc-Pab was positive but decreased the IVC venous return when Pivc - Pab was negative. The value of Pivc - Pab that separated net increases from decreases in venous return was 1.00 +/- 0.72 (SE) mmHg (n = 6). An increase in Pivc did not influence the femoral venous pressure when Pivc was lower than the sum of Pab and a constant, 0.96 +/- 0.70 mmHg (n = 6), consistent with presence of a waterfall. These results agreed closely with the predictions of the model and its computer simulation. The abdominal venous compartment appears to function with changes in Pab either as a capacitor in zone 3 conditions or as a collapsible Starling resistor with little wall tone in zone 2 conditions.

Validation of Repeated Endothelial Function Measurements Using EndoPAT in Stroke

DEFF Research Database (Denmark)

Hansen, Aina S; Butt, Jawad H; Holm-Yildiz, Sonja

2017-01-01

BACKGROUND: Decreased endothelial function (EF) may be a prognostic marker for stroke. Measuring pharmacological effects on EF may be of interest in the development of personalized medicine for stroke prevention. In this study, we assessed the reliability of repeated EF measurements using a pulse......%, mean age 35.85 ± 3.47 years) and 21 stroke patients (men 52%, mean age 66.38 ± 2.85 years, and mean NIHSS 4.09 ± 0.53) under standardized conditions. EF was measured as the reactive hyperemia index (RHI), logarithm of RHI (lnRHI), and Framingham RHI (fRHI). Measurements were separated by 1.5 and 24 h...

Vascular endothelial growth factors: multitasking functionality in metabolism, health and disease.

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Smith, Gina A; Fearnley, Gareth W; Harrison, Michael A; Tomlinson, Darren C; Wheatcroft, Stephen B; Ponnambalam, Sreenivasan

2015-07-01

Vascular endothelial growth factors (VEGFs) bind to VEGF receptor tyrosine kinases (VEGFRs). The VEGF and VEGFR gene products regulate diverse regulatory pathways in mammalian development, health and disease. The interaction between a particular VEGF and its cognate VEGFR activates multiple signal transduction pathways which regulate different cellular responses including metabolism, gene expression, proliferation, migration, and survival. The family of VEGF isoforms regulate vascular physiology and promote tissue homeostasis. VEGF dysfunction is implicated in major chronic disease states including atherosclerosis, diabetes, and cancer. More recent studies implicate a strong link between response to VEGF and regulation of vascular metabolism. Understanding how this family of multitasking cytokines regulates cell and animal function has implications for treating many different diseases.

Protocol for the realization of venous mapping by chronic venous insufficiency in lower limbs under sonographic guide

International Nuclear Information System (INIS)

Blanco Rojas, Diego Jose

2013-01-01

The current state of knowledge is reviewed with respect to the realization of lower limbs venous mapping. Venous mapping is obtained by the use of color and spectral Doppler ultrasound. Doppler ultrasound has provided a precise graphical representation of the superficial and deep venous systems. The performance of the venous mapping is considered essential for the correct handling of venous diseases. The anatomical and pathophysiological basic concepts are defined to realize the sonographic assessment of the veins of the lower limbs. The required technical aspects are revised for the realization of sonographic exploration of the patient with venous insufficiency. Sonographic findings are characterized to support the diagnostic of venous insufficiency of the lower limbs. The CEAP (clinical-etiologic-anatomic-pathophysiologic) classification is utilized to differentiate forms and degrees of severity of the disorder, and has allowed an interinstitutional comparison in clinical studies, the evaluation of treatment and monitoring of patients. A proposal is designed to perform reports that have served of guide surgical to vascular surgeons [es

Human cerebral venous outflow pathway depends on posture and central venous pressure

DEFF Research Database (Denmark)

Gisolf, J; van Lieshout, J J; van Heusden, K

2004-01-01

Internal jugular veins are the major cerebral venous outflow pathway in supine humans. In upright humans the positioning of these veins above heart level causes them to collapse. An alternative cerebral outflow pathway is the vertebral venous plexus. We set out to determine the effect of posture...... and during a Valsalva manoeuvre in both body positions, correlate highly with model simulation of the jugular cross-sectional area (R(2) = 0.97). The results suggest that the cerebral venous flow distribution depends on posture and CVP: in supine humans the internal jugular veins are the primary pathway...

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

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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.

Weight loss improves biomarkers endothelial function and systemic ...

African Journals Online (AJOL)

loskeletal disorders, and intake of medications affect the endothelial ... tion (4 patients had work related schedule problems and. 2 patient ... was measured on a calibrated balance scale to the nearest ... ing program was performed at 70% of the individual age- ... their ordinary life style and received no exercise and diet.

Colorectal cancer with venous tumor thrombosis

OpenAIRE

Kensuke Otani; Soichiro Ishihara; Keisuke Hata; Koji Murono; Kazuhito Sasaki; Koji Yasuda; Takeshi Nishikawa; Toshiaki Tanaka; Tomomichi Kiyomatsu; Kazushige Kawai; Hiroaki Nozawa; Hironori Yamaguchi; Toshiaki Watanabe

2018-01-01

Summary: Colorectal cancer is seldom accompanied by venous tumor thrombosis, and little is known about the features of venous tumor thrombosis in colorectal cancer. However, some reports show that colorectal cancer patients can develop venous tumor thrombosis and warn clinicians not to overlook this complication. In this report, we perform a review of 43 previously reported cases and investigate the characteristics of colorectal cancer accompanied by venous tumor thrombosis. The histological ...

Sympathetic Innervation Promotes Arterial Fate by Enhancing Endothelial ERK Activity.

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Pardanaud, Luc; Pibouin-Fragner, Laurence; Dubrac, Alexandre; Mathivet, Thomas; English, Isabel; Brunet, Isabelle; Simons, Michael; Eichmann, Anne

2016-08-19

Arterial endothelial cells are morphologically, functionally, and molecularly distinct from those found in veins and lymphatic vessels. How arterial fate is acquired during development and maintained in adult vessels is incompletely understood. We set out to identify factors that promote arterial endothelial cell fate in vivo. We developed a functional assay, allowing us to monitor and manipulate arterial fate in vivo, using arteries isolated from quails that are grafted into the coelom of chick embryos. Endothelial cells migrate out from the grafted artery, and their colonization of host arteries and veins is quantified. Here we show that sympathetic innervation promotes arterial endothelial cell fate in vivo. Removal of sympathetic nerves decreases arterial fate and leads to colonization of veins, whereas exposure to sympathetic nerves or norepinephrine imposes arterial fate. Mechanistically, sympathetic nerves increase endothelial ERK (extracellular signal-regulated kinase) activity via adrenergic α1 and α2 receptors. These findings show that sympathetic innervation promotes arterial endothelial fate and may lead to novel approaches to improve arterialization in human disease. © 2016 American Heart Association, Inc.

Endothelial cell preservation at hypothermic to normothermic conditions using clinical and experimental organ preservation solutions

NARCIS (Netherlands)

Post, Ivo C. J. H.; de Boon, Wadim M. I.; Heger, Michal; van Wijk, Albert C. W. A.; Kroon, Jeffrey; van Buul, Jaap D.; van Gulik, Thomas M.

2013-01-01

Endothelial barrier function is pivotal for the outcome of organ transplantation. Since hypothermic preservation (gold standard) is associated with cold-induced endothelial damage, endothelial barrier function may benefit from organ preservation at warmer temperatures. We therefore assessed

Lipid rafts regulate PCB153-induced disruption of occludin and brain endothelial barrier function through protein phosphatase 2A and matrix metalloproteinase-2

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Eum, Sung Yong, E-mail: seum@miami.edu; Jaraki, Dima; András, Ibolya E.; Toborek, Michal

2015-09-15

Occludin is an essential integral transmembrane protein regulating tight junction (TJ) integrity in brain endothelial cells. Phosphorylation of occludin is associated with its localization to TJ sites and incorporation into intact TJ assembly. The present study is focused on the role of lipid rafts in polychlorinated biphenyl (PCB)-induced disruption of occludin and endothelial barrier function. Exposure of human brain endothelial cells to 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB153) induced dephosphorylation of threonine residues of occludin and displacement of occludin from detergent-resistant membrane (DRM)/lipid raft fractions within 1 h. Moreover, lipid rafts modulated the reduction of occludin level through activation of matrix metalloproteinase 2 (MMP-2) after 24 h PCB153 treatment. Inhibition of protein phosphatase 2A (PP2A) activity by okadaic acid or fostriecin markedly protected against PCB153-induced displacement of occludin and increased permeability of endothelial cells. The implication of lipid rafts and PP2A signaling in these processes was further defined by co-immunoprecipitation of occludin with PP2A and caveolin-1, a marker protein of lipid rafts. Indeed, a significant MMP-2 activity was observed in lipid rafts and was increased by exposure to PCB153. The pretreatment of MMP-2 inhibitors protected against PCB153-induced loss of occludin and disruption of lipid raft structure prevented the increase of endothelial permeability. Overall, these results indicate that lipid raft-associated processes, such as PP2A and MMP-2 activation, participate in PCB153-induced disruption of occludin function in brain endothelial barrier. This study contributes to a better understanding of the mechanisms leading to brain endothelial barrier dysfunction in response to exposure to environmental pollutants, such as ortho-substituted PCBs. - Highlights: • PCB153 disturbed human brain endothelial barrier through disruption of occludin. • Lipid raft-associated PP

Endothelial Function as a Possible Significant Determinant of Cardiac Function during Exercise in Patients with Structural Heart Disease

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Bonpei Takase

2009-01-01

Full Text Available This study was investigated the role that endothelial function and systemic vascular resistance (SVR play in determining cardiac function reserve during exercise by a new ambulatory radionuclide monitoring system (VEST in patients with heart disease. The study population consisted of 32 patients. The patients had cardiopulmonary stress testing using the treadmill Ramp protocol and the VEST. The anaerobic threshold (AT was autodetermined using the V-slope method. The SVR was calculated by determining the mean blood pressure/cardiac output. Flow-mediated vasodilation (FMD was measured in the brachial artery to evaluate endotheilial function. FMD and the percent change f'rom rest to AT in SVR correlated with those from rest to AT in ejection fraction and peak ejection ratio by VEST, respectively. Our findings suggest that FMD in the brachial artery and the SVR determined by VEST in patients with heart disease can possibly reflect cardiac function reserve during aerobic exercise.

Diagnosis and endovascular treatment of multiple cerebral venous and venous sinuses thrombosis

International Nuclear Information System (INIS)

Li Baomin; Zhang Ji; Yin Ling; Huang Xusheng; Jiang Jinli; Liu Jun; Lang Senyang; Zhou Dingbiao; Zhu Ke

2000-01-01

Objective: Eighty-five cases with multiple cerebral venous and venous sinuses thrombosis including the diagnosis and endovascular therapy were reported. Methods: The long T2 and short T1 signals in the related regions of multiple venous sinuses on MRI and prolonged blood circulation time of the brain with tortuous dilatation of vein in angiography were the important characteristics for the diagnosis. Of the 85 cases, the treatment procedures were consisted of injecting urokinase intermittently via common carotid artery and intra-sinus contact thrombolysis as well as warfarin intake orally. Results: Intracranial pressure of 80 cases reduced down between 230 and 300 mm H 2 O, and clinical deficits were markedly improved within 10 days. Re-angiography of 18 cases revealed recanalization partly in 5 cases and circulation time appeared near normal i 8 cases during one week after therapy. Conclusions: Combined intraarterial thrombolysis consecutively with general anticoagulation for the treatment of multiple thrombosis in cerebral venous sinuses may be one of the effective means

Abrogation of Antibody-Induced Arthritis in Mice by a Self-Activating Viridin Prodrug and Association With Impaired Neutrophil and Endothelial Cell Function

Science.gov (United States)

Stangenberg, Lars; Ellson, Chris; Cortez-Retamozo, Virna; Ortiz-Lopez, Adriana; Yuan, Hushan; Blois, Joseph; Smith, Ralph A.; Yaffe, Michael B.; Weissleder, Ralph; Benoist, Christophe; Mathis, Diane; Josephson, Lee; Mahmood, Umar

2009-01-01

Objective To test a novel self-activating viridin (SAV) prodrug that slowly releases wortmannin, a potent phosphoinositide 3-kinase inhibitor, in a model of antibody-mediated inflammatory arthritis. Methods The SAV prodrug was administered to K/BxN mice or to C57BL/6 (B6) mice that had been injected with K/BxN serum. Ankle thickness was measured, and histologic changes were scored after a 10-day disease course (serum-transfer arthritis). Protease activity was measured by a near-infrared imaging approach using a cleavable cathepsin–selective probe. Further near-infrared imaging techniques were used to analyze early changes in vascular permeability after serum injection, as well as neutrophil–endothelial cell interactions. Neutrophil functions were assessed using an oxidative burst assay as well as a degranulation assay. Results SAV prevented ankle swelling in mice with serum-transfer arthritis in a dose-dependent manner. It also markedly reduced the extent of other features of arthritis, such as protease activity and histology scores for inflammation and joint erosion. Moreover, SAV was an effective therapeutic agent. The underlying mechanisms for the antiinflammatory activity were manifold. Endothelial permeability after serum injection was reduced, as was firm neutrophil attachment to endothelial cells. Endothelial cell activation by tumor necrosis factor α was impeded by SAV, as measured by the expression of vascular cell adhesion molecule. Crucial neutrophil functions, such as generation of reactive oxygen species and degranulation of protease-laden vesicles, were decreased by SAV administration. Conclusion A novel SAV prodrug proved strongly antiinflammatory in a murine model of antibody-induced inflammatory arthritis. Its activity could be attributed, at least in part, to the inhibition of neutrophil and endothelial cell functions. PMID:19644878

Endothelial glycocalyx integrity is preserved in young, healthy men during a single bout of strenuous physical exercise.

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Majerczak, J; Duda, K; Chlopicki, S; Bartosz, G; Zakrzewska, A; Balcerczyk, A; Smoleński, R T; Zoladz, J A

2016-06-20

In the present study we aimed to evaluate whether oxidative stress and inflammation induced by strenuous exercise affect glycocalyx integrity and endothelial function. Twenty one young, untrained healthy men performed a maximal incremental cycling exercise - until exhaustion. Markers of glycocalyx shedding (syndecan-1, heparan sulfate and hyaluronic acid), endothelial status (nitric oxide and prostacyclin metabolites - nitrate, nitrite, 6-keto-prostaglandin F(1alpha)), oxidative stress (8-oxo-2'-deoxyguanosine) and antioxidant capacity (uric acid, non-enzymatic antioxidant capacity) as well as markers of inflammation (sVCAM-1 and sICAM-1) were analyzed in venous blood samples taken at rest and at the end of exercise. The applied strenuous exercise caused a 5-fold increase in plasma lactate and hypoxanthine concentrations (p<0.001), a fall in plasma uric acid concentration and non-enzymatic antioxidant capacity (p<10(-4)), accompanied by an increase (p=0.003) in sVCAM-1 concentration. Plasma 6-keto-prostaglandin F(1alpha) concentration increased (p=0.006) at exhaustion, while nitrate and nitrite concentrations were not affected. Surprisingly, no significant changes in serum syndecan-1 and heparan sulfate concentrations were observed. We have concluded, that a single bout of severe-intensity exercise is well accommodated by endothelium in young, healthy men as it neither results in evident glycocalyx disruption nor in the impairment of nitric oxide and prostacyclin production.

Regional differences in endothelial cell cytoskeleton, junctional proteins and phosphorylated tyrosine labeling in the porcine vortex vein system.

Science.gov (United States)

Tan, Priscilla Ern Zhi; Yu, Paula K; Yang, Hongfang; Cringle, Stephen J; Yu, Dao-Yi

2018-07-01

We previously demonstrated endothelial phenotype heterogeneity in the vortex vein system. This study is to further determine whether regional differences are present in the cytoskeleton, junctional proteins and phosphorylated tyrosine labeling within the system. The vortex vein system of twenty porcine eyes was perfused with labels for f-actin, claudin-5, VE-Cadherin, phosphorylated tyrosine and nucleic acid. The endothelial cells of eight different regions (choroidal veins, pre-ampulla, anterior ampulla, mid-ampulla, posterior ampulla, post-ampulla, intra-scleral canal and the extra-ocular vortex vein) were studied using confocal microscopy. There were regional differences in the endothelial cell structures. Cytoskeleton labeling was relatively even in intensity throughout Regions 1 to 6. Overall VE-Cadherin had a non-uniform distribution and thicker width endothelial cell border staining than claudin-5. Progressing downstream there was an increased variation in thickness of VE-cadherin labeling. There was an overlap in phosphorylated tyrosine and VE-Cadherin labeling in the post-ampulla, intra-scleral canal and extra-ocular vortex vein. Intramural cells were observed that were immune-positive for VE-Cadherin and phosphorylated tyrosine. There were significant differences in the number of intramural cells in different regions. Significant regional differences with endothelial cell labeling of cytoskeleton, junction proteins, and phosphorylated tyrosine were found within the vortex vein system. These findings support existing data on endothelial cell phenotype heterogeneity, and may aid in the knowledge of venous pathologies by understanding regions of vulnerability to endothelial damage within the vortex vein system. It could be valuable to further investigate and characterize the VE-cadherin and phosphotyrosine immune-positive intramural cells. Copyright © 2018. Published by Elsevier Ltd.

Role of glutathione biosynthesis in endothelial dysfunction and fibrosis

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Cristina Espinosa-Díez

2018-04-01

Full Text Available Glutathione (GSH biosynthesis is essential for cellular redox homeostasis and antioxidant defense. The rate-limiting step requires glutamate-cysteine ligase (GCL, which is composed of the catalytic (GCLc and the modulatory (GCLm subunits. To evaluate the contribution of GCLc to endothelial function we generated an endothelial-specific Gclc haplo-insufficient mouse model (Gclc e/+ mice. In murine lung endothelial cells (MLEC derived from these mice we observed a 50% reduction in GCLc levels compared to lung fibroblasts from the same mice. MLEC obtained from haplo-insufficient mice showed significant reduction in GSH levels as well as increased basal and stimulated ROS levels, reduced phosphorylation of eNOS (Ser 1177 and increased eNOS S-glutathionylation, compared to MLEC from wild type (WT mice. Studies in mesenteric arteries demonstrated impaired endothelium-dependent vasodilation in Gclc(e/+ male mice, which was corrected by pre-incubation with GSH-ethyl-ester and BH4. To study the contribution of endothelial GSH synthesis to renal fibrosis we employed the unilateral ureteral obstruction model in WT and Gclc(e/+ mice. We observed that obstructed kidneys from Gclc(e/+ mice exhibited increased deposition of fibrotic markers and reduced Nrf2 levels. We conclude that the preservation of endothelial GSH biosynthesis is not only critical for endothelial function but also in anti-fibrotic responses. Keywords: Glutamate-cysteine ligase, ROS, Glutathione, Endothelial dysfunction, Kidney Fibrosis

Chronic aerobic exercise training attenuates aortic stiffening and endothelial dysfunction through preserving aortic mitochondrial function in aged rats.

Science.gov (United States)

Gu, Qi; Wang, Bing; Zhang, Xiao-Feng; Ma, Yan-Ping; Liu, Jian-Dong; Wang, Xiao-Ze

2014-08-01

Aging leads to large vessel arterial stiffening and endothelial dysfunction, which are important determinants of cardiovascular risk. The aim of present work was to assess the effects of chronic aerobic exercise training on aortic stiffening and endothelial dysfunction in aged rats and investigate the underlying mechanism about mitochondrial function. Chronic aerobic exercise training attenuated aortic stiffening with age marked by reduced collagen concentration, increased elastin concentration and reduced pulse wave velocity (PWV), and prevented aging-related endothelial dysfunction marked by improved endothelium-mediated vascular relaxation of aortas in response to acetylcholine. Chronic aerobic exercise training abated oxidative stress and nitrosative stress in aortas of aged rats. More importantly, we found that chronic aerobic exercise training in old rats preserved aortic mitochondrial function marked by reduced reactive oxygen species (ROS) formation and mitochondrial swelling, increased ATP formation and mitochondrial DNA content, and restored activities of complexes I and III and electron-coupling capacity between complexes I and III and between complexes II and III. In addition, it was found that chronic aerobic exercise training in old rats enhanced protein expression of uncoupling protein 2 (UCP-2), peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α), manganese superoxide dismutase (Mn-SOD), aldehyde dehydrogenase 2 (ALDH-2), prohibitin (PHB) and AMP-activated kinase (AMPK) phosphorylation in aortas. In conclusion, chronic aerobic exercise training preserved mitochondrial function in aortas, which, at least in part, explained the aorta-protecting effects of exercise training in aging. Copyright © 2014 Elsevier Inc. All rights reserved.

Endothelial cell seeding on crosslinked collagen : Effects of crosslinking on endothelial cell proliferation and functional parameters

NARCIS (Netherlands)

Wissink, MJB; van Luyn, MJA; Dijk, F; Poot, AA; Engbers, GHM; Beugeling, T; van Aken, WG; Feijen, J

Endothelial cell seeding, a promising method to improve the performance of small-diameter vascular grafts, requires a suitable substrate, such as crosslinked collagen. Commonly used crosslinking agents such as glutaraldehyde and formaldehyde cause, however, cytotoxic reactions and thereby hamper

Transposition of cephalic vein to rescue hemodialysis access arteriovenous fistula and treat symptomatic central venous obstruction

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Felipe Jose Skupien

2014-03-01

Full Text Available It is known that stenosis or central venous obstruction affects 20 to 50% of patients who undergo placement of catheters in central veins. For patients who are given hemodialysis via upper limbs, this problem causes debilitating symptoms and increases the risk of loss of hemodialysis access. We report an atypical case of treatment of a dialysis patient with multiple comorbidities, severe swelling and pain in the right upper limb (RUL, few alternative sites for hemodialysis vascular access, a functioning brachiobasilic fistula in the RUL and severe venous hypertension in the same limb, secondary to central vein occlusion of the internal jugular vein and right brachiocephalic trunk. The alternative surgical treatment chosen was to transpose the RUL cephalic vein, forming a venous necklace at the anterior cervical region, bypassing the site of venous occlusion. In order to achieve this, we dissected the cephalic vein in the right arm to its junction with the axillary vein, devalved the cephalic vein and anastomosed it to the contralateral external jugular vein, providing venous drainage to the RUL, alleviating symptoms of venous hypertension and preserving function of the brachiobasilic fistula.

Nutraceuticals in cardiovascular prevention: lessons from studies on endothelial function.

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Zuchi, Cinzia; Ambrosio, Giuseppe; Lüscher, Thomas F; Landmesser, Ulf

2010-08-01

An "unhealthy" diet is considered as a main cause of increased atherosclerotic cardiovascular disease in the industrialized countries. There is a substantial interest in the potential cardiovascular protective effects of "nutraceuticals," that is food-derived substances that exert beneficial health effects. The correct understanding of cardiovascular effects of these compounds will have important implications for cardiovascular prevention strategies. Endothelial dysfunction is thought to play an important role in development and progression of atherosclerosis, and the characterization of the endothelial effects of several nutraceuticals may provide important insights into their potential role in cardiovascular prevention. At the same time, the analysis of the endothelial effects of nutraceuticals may also provide valuable insights into mechanisms of why certain nutraceuticals may not be effective in cardiovascular prevention, and it may aid in the identification of food-derived substances that may have detrimental cardiovascular effects. These findings further support the notion that nutraceuticals do need support from large clinical outcome trials with respect to their efficacy and safety profile for cardiovascular prevention, before their widespread use can be recommended. In fact, the term nutraceutical was coined to encourage an extensive and profound research activity in this field, and numerous large-scale clinical outcome trials to examine the effects of nutraceuticals on cardiovascular events have now been performed or are still ongoing. Whereas it is possible that single nutraceuticals may be effective in cardiovascular prevention, this field of research provides also valuable insights into which food components may be particularly important for cardiovascular prevention, to further advice the composition of a particularly healthy diet. The present review summarizes recent studies on the endothelial effects of several nutraceuticals, that have been

Cardiac microvascular endothelial cells express a functional Ca+ -sensing receptor.

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Berra Romani, Roberto; Raqeeb, Abdul; Laforenza, Umberto; Scaffino, Manuela Federica; Moccia, Francesco; Avelino-Cruz, Josè Everardo; Oldani, Amanda; Coltrini, Daniela; Milesi, Veronica; Taglietti, Vanni; Tanzi, Franco

2009-01-01

The mechanism whereby extracellular Ca(2+) exerts the endothelium-dependent control of vascular tone is still unclear. In this study, we assessed whether cardiac microvascular endothelial cells (CMEC) express a functional extracellular Ca(2+)-sensing receptor (CaSR) using a variety of techniques. CaSR mRNA was detected using RT-PCR, and CaSR protein was identified by immunocytochemical analysis. In order to assess the functionality of the receptor, CMEC were loaded with the Ca(2+)-sensitive fluorochrome, Fura-2/AM. A number of CaSR agonists, such as spermine, Gd(3+), La(3+) and neomycin, elicited a heterogeneous intracellular Ca(2+) signal, which was abolished by disruption of inositol 1,4,5-trisphosphate (InsP(3)) signaling and by depletion of intracellular stores with cyclopiazonic acid. The inhibition of the Na(+)/Ca(2+) exchanger upon substitution of extracellular Na(+) unmasked the Ca(2+) signal triggered by an increase in extracellular Ca(2+) levels. Finally, aromatic amino acids, which function as allosteric activators of CaSR, potentiated the Ca(2+) response to the CaSR agonist La(3+). These data provide evidence that CMEC express CaSR, which is able to respond to physiological agonists by mobilizing Ca(2+) from intracellular InsP(3)-sensitive stores. Copyright 2008 S. Karger AG, Basel.

Significance of venous anastomosis in fingertip replantation.

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Hattori, Yasunori; Doi, Kazuteru; Ikeda, Keisuke; Abe, Yukio; Dhawan, Vikas

2003-03-01

Adequate venous outflow is the most important factor for successful fingertip replantation. The authors have attempted venous anastomosis in all cases of fingertip replantation to overcome postoperative congestion. In this article, the significance of venous repair for fingertip replantation is described from the authors' results of 64 complete fingertip amputations in 55 consecutive patients, which were replanted from January of 1996 to June of 2001. The overall survival rate was 86 percent. Of the 44 replantations in zone I, 37 survived, and the success rate was 84 percent. Of the 20 replantations in zone II, 18 survived, and the success rate was 90 percent. Venous anastomosis was attempted in all cases, but it was possible in 39 zone I and in all zone II replantations. For arterial repair, vein grafts were necessary in 17 of the 44 zone I and in one of the 20 zone II replantations; for venous repair, they were necessary in six zone I replantations and one zone II replantation. Postoperative vascular complications occurred in 15 replantations. There were five cases of arterial thrombosis and 10 cases of venous congestion. Venous congestion occurred in nine zone I and one zone II replantations. In five of these 10 replantations, venous anastomosis was not possible. In another five replantations, venous outflow was established at the time of surgery, but occlusion occurred subsequently. Except for the five failures resulting from arterial thrombosis, successful venous repair was possible in 49 of 59 replantations (83 percent). Despite the demand for skillful microsurgical technique and longer operation time, the authors' results using venous anastomosis in successful fingertip replantations are encouraging. By performing venous anastomosis, external bleeding can be avoided and a higher survival rate can be achieved. Venous anastomosis for fingertip replantation is a reliable and worthwhile procedure.

Obesity suppresses circulating level and function of endothelial progenitor cells and heart function

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Tsai Tzu-Hsien

2012-07-01

Full Text Available Abstract Background and aim This study tested the hypothesis that obesity suppresses circulating number as well as the function of endothelial progenitor cells (EPCs and left ventricular ejection fraction (LVEF. Methods High fat diet (45 Kcal% fat was given to 8-week-old C57BL/6 J mice (n = 8 for 20 weeks to induce obesity (group 1. Another age-matched group (n = 8 were fed with control diet for 20 weeks as controls (group 2. The animals were sacrificed at the end of 20 weeks after obesity induction. Results By the end of study period, the heart weight, body weight, abdominal fat weight, serum levels of total cholesterol and fasting blood sugar were remarkably higher in group 1 than in group 2 (all p Conclusions Obesity diminished circulating EPC level, impaired the recovery of damaged endothelium, suppressed EPC angiogenesis ability and LVEF, and increased LV remodeling.

Retrograde shear rate in formerly preeclamptic and healthy women before and after exercise training: relationship with endothelial function.

NARCIS (Netherlands)

Scholten, R.R.; Spaanderman, M.E.A.; Green, D.J.; Hopman, M.T.E.; Thijssen, D.H.J.

2014-01-01

Blood flow patterns in conduit arteries characterized by high levels of retrograde shear stress can be detrimental for vascular health. In this study we examined whether retrograde shear rate and endothelial function are related in healthy and formerly preeclamptic (PE) women and whether this

Neuronal sFlt1 and Vegfaa determine venous sprouting and spinal cord vascularization

DEFF Research Database (Denmark)

Wild, Raphael; Klems, Alina; Takamiya, Masanari

2017-01-01

Formation of organ-specific vasculatures requires cross-talk between developing tissue and specialized endothelial cells. Here we show how developing zebrafish spinal cord neurons coordinate vessel growth through balancing of neuron-derived Vegfaa, with neuronal sFlt1 restricting Vegfaa......-Kdrl mediated angiogenesis at the neurovascular interface. Neuron-specific loss of flt1 or increased neuronal vegfaa expression promotes angiogenesis and peri-neural tube vascular network formation. Combining loss of neuronal flt1 with gain of vegfaa promotes sprout invasion into the neural tube. On loss...... of neuronal flt1, ectopic sprouts emanate from veins involving special angiogenic cell behaviours including nuclear positioning and a molecular signature distinct from primary arterial or secondary venous sprouting. Manipulation of arteriovenous identity or Notch signalling established that ectopic sprouting...

Sickle erythrocytes inhibit human endothelial cell DNA synthesis

International Nuclear Information System (INIS)

Weinstein, R.; Zhou, M.A.; Bartlett-Pandite, A.; Wenc, K.

1990-01-01

Patients with sickle cell anemia experience severe vascular occlusive phenomena including acute pain crisis and cerebral infarction. Obstruction occurs at both the microvascular and the arterial level, and the clinical presentation of vascular events is heterogeneous, suggesting a complex etiology. Interaction between sickle erythrocytes and the endothelium may contribute to vascular occlusion due to alteration of endothelial function. To investigate this hypothesis, human vascular endothelial cells were overlaid with sickle or normal erythrocytes and stimulated to synthesize DNA. The erythrocytes were sedimented onto replicate monolayers by centrifugation for 10 minutes at 17 g to insure contact with the endothelial cells. Incorporation of 3H-thymidine into endothelial cell DNA was markedly inhibited during contact with sickle erythrocytes. This inhibitory effect was enhanced more than twofold when autologous sickle plasma was present during endothelial cell labeling. Normal erythrocytes, with or without autologous plasma, had a modest effect on endothelial cell DNA synthesis. When sickle erythrocytes in autologous sickle plasma were applied to endothelial monolayers for 1 minute, 10 minutes, or 1 hour and then removed, subsequent DNA synthesis by the endothelial cells was inhibited by 30% to 40%. Although adherence of sickle erythrocytes to the endothelial monolayers was observed under these experimental conditions, the effect of sickle erythrocytes on endothelial DNA synthesis occurred in the absence of significant adherence. Hence, human endothelial cell DNA synthesis is partially inhibited by contact with sickle erythrocytes. The inhibitory effect of sickle erythrocytes occurs during a brief (1 minute) contact with the endothelial monolayers, and persists for at least 6 hours of 3H-thymidine labeling

Pentoxifylline, inflammation, and endothelial function in HIV-infected persons: a randomized, placebo-controlled trial.

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Samir K Gupta

Full Text Available Untreated HIV may increase the risk of cardiovascular events. Our preliminary in vitro and in vivo research suggests that pentoxifylline (PTX reduces vascular inflammation and improves endothelial function in HIV-infected persons not requiring antiretroviral therapy.We performed a randomized, placebo-controlled trial of PTX 400 mg orally thrice daily for 8 weeks in 26 participants. The primary endpoint was change in flow-mediated dilation (FMD of the brachial artery after 8 weeks. Nitroglycerin-mediated dilation (NTGMD and circulating markers of inflammation, cellular immune activation, coagulation, and metabolism were also assessed.The difference in mean absolute change (SD in FMD after 8 weeks between the placebo [-1.06 (1.45%] and PTX [-1.93 (3.03%] groups was not significant (P = 0.44. No differences in NTGMD were observed. The only significant between-group difference in the changes in biomarkers from baseline to week 8 was in soluble tumor necrosis factor receptor-1 (sTNFRI [-83.2 pg/mL in the placebo group vs. +65.9 pg/mL in the PTX group; P = 0.03]. PTX was generally well-tolerated.PTX did not improve endothelial function and unexpectedly increased the inflammatory biomarker sTNFRI in HIV-infected participants not requiring antiretroviral therapy. Additional interventional research is needed to reduce inflammation and cardiovascular risk in this population.ClinicalTrials.gov NCT00796822.

Venous abnormalities demonstrated by computed tomography

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Ishikawa, T; Tsukune, Y; Ashida, H; Tokuda, M; Oyama, Y [St. Marianna Univ., Kawasaki, Kanagawa (Japan). School of Medicine

1980-05-01

CT is capable of demonstrating various venous changes. However, little have been described on this subject in the literature. Examples of various venous abnormalities such as obstructed jugular vein, superior and inferior vena cava (IVC), tumor invasion of IVC and renal vein and venous changes in portal hypertension were presented. It was stressed that noninvasive CT is a good tool in diagnosis of some of venous changes and may be able to eliminate angiography in such cases.

Human Brain Microvascular Endothelial Cells and Umbilical Vein Endothelial Cells Differentially Facilitate Leukocyte Recruitment and Utilize Chemokines for T Cell Migration

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Shumei Man

2008-01-01

Full Text Available Endothelial cells that functionally express blood brain barrier (BBB properties are useful surrogates for studying leukocyte-endothelial cell interactions at the BBB. In this study, we compared two different endothelial cellular models: transfected human brain microvascular endothelial cells (THBMECs and human umbilical vein endothelial cells (HUVECs. With each grow under optimal conditions, confluent THBMEC cultures showed continuous occludin and ZO-1 immunoreactivity, while HUVEC cultures exhibited punctate ZO-1 expression at sites of cell-cell contact only. Confluent THBMEC cultures on 24-well collagen-coated transwell inserts had significantly higher transendothelial electrical resistance (TEER and lower solute permeability than HUVECs. Confluent THBMECs were more restrictive for mononuclear cell migration than HUVECs. Only THBMECs utilized abluminal CCL5 to facilitate T-lymphocyte migration in vitro although both THBMECs and HUVECs employed CCL3 to facilitate T cell migration. These data establish baseline conditions for using THBMECs to develop in vitro BBB models for studying leukocyte-endothelial interactions during neuroinflammation.

[Echo-tracking technology for evaluating femoral artery endothelial function in patients with Grave's disease].

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Wei, Wei; Wang, Jingyuan; Zhao, Qiaoling; Yang, Jinru

2012-10-01

To assess the value of echo-tracking technology in evaluating endothelial function of the femoral artery in patients with Grave's disease. Thirty-four patients with Grave's disease patients and 30 normal adults as controls were recruited in this study. The intima-media thickness (IMT), arterial stiffness (β), pressure strain elastic modulus (Ep), arterial compliance (AC), pulse wave conducting velocity (PWVβ) and augmentation index (AI) parameters were examined using echo-tracking technology for evaluating the right femoral arterial elasticity. Compared with the control subjects, the patients with Grave's disease showed significantly increased β, Ep, and PWVβ and significantly decreased AC (P0.05). In patients with Grave's disease, β and Ep were positively correlated with FT3, FT4, TT3, TT4, and PWVβ was positively correlated with FT3 and FT4. Echo-tracking technology can provide more accurate quantitative evidences for early diagnosis of femoral artery endothelial dysfunction in patients with Grave's disease, but the influence of procedural factors on the measurement accuracy should be considered in the evaluation.

Low Immunogenic Endothelial Cells Maintain Morphological and Functional Properties Required for Vascular Tissue Engineering.

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Lau, Skadi; Eicke, Dorothee; Carvalho Oliveira, Marco; Wiegmann, Bettina; Schrimpf, Claudia; Haverich, Axel; Blasczyk, Rainer; Wilhelmi, Mathias; Figueiredo, Constança; Böer, Ulrike

2018-03-01

The limited availability of native vessels suitable for the application as hemodialysis shunts or bypass material demands new strategies in cardiovascular surgery. Tissue-engineered vascular grafts containing autologous cells are considered ideal vessel replacements due to the low risk of rejection. However, endothelial cells (EC), which are central components of natural blood vessels, are difficult to obtain from elderly patients of poor health. Umbilical cord blood represents a promising alternative source for EC, but their allogeneic origin corresponds with the risk of rejection after allotransplantation. To reduce this risk, the human leukocyte antigen class I (HLA I) complex was stably silenced by lentiviral vector-mediated RNA interference (RNAi) in EC from peripheral blood and umbilical cord blood and vein. EC from all three sources were transduced by 93.1% ± 4.8% and effectively, HLA I-silenced by up to 67% compared to nontransduced (NT) cells or transduced with a nonspecific short hairpin RNA, respectively. Silenced EC remained capable to express characteristic endothelial surface markers such as CD31 and vascular endothelial cadherin important for constructing a tight barrier, as well as von Willebrand factor and endothelial nitric oxide synthase important for blood coagulation and vessel tone regulation. Moreover, HLA I-silenced EC were still able to align under unidirectional flow, to take up acetylated low-density lipoprotein, and to form capillary-like tube structures in three-dimensional fibrin gels similar to NT cells. In particular, addition of adipose tissue-derived mesenchymal stem cells significantly improved tube formation capability of HLA I-silenced EC toward long and widely branched vascular networks necessary for prevascularizing vascular grafts. Thus, silencing HLA I by RNAi represents a promising technique to reduce the immunogenic potential of EC from three different sources without interfering with EC-specific morphological and

The Expression Profiles of Lysophospholipid Receptors (LPLRs in Different Endothelial Cells

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Yu-Wei Lee

2006-03-01

Full Text Available Sphingosine-1-phosphate (S1P and lysophosphatidic acid (LPA are two bioactive lysophospholipids (LPLs, stored primarily in platelets and released during platelet activation. Both LPLs are capable of regulating endothelial cell functions. The physiological functions of S1P and LPA are mediated by interacting with eight different G-protein coupled receptors: S1P1 through 5 and LPA1 through 3, which activate three different heterotrimeric GTP proteins－including Gi、Gq and G(12/13. The expression of LPL receptors in endothelial cells would affect the responses of S1P and LPA to these cells. There is no previous report discussing the expression profiles of LPL receptors in different endothelial cells from various species. In this study, we aim to investigate the expression profiles of S1P and LPA receptors in different endothelial cells isolated from human, rat, mouse and bovine origin. We used RT-PCR to determine LPLs receptors expression profiles in different endothelial cells. Our results indicated that endothelial cells from various species express different LPL receptors. Endothelial cells isolated from the same source of different species also had different LPLs receptors expression profiles. Therefore, different endothelial cells should respond to LPLs in different manners.

Endothelial glycocalyx dysfunction in disease: albuminuria and increased microvascular permeability.

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Salmon, Andrew H J; Satchell, Simon C

2012-03-01

Appreciation of the glomerular microcirculation as a specialized microcirculatory bed, rather than as an entirely separate entity, affords important insights into both glomerular and systemic microvascular pathophysiology. In this review we compare regulation of permeability in systemic and glomerular microcirculations, focusing particularly on the role of the endothelial glycocalyx, and consider the implications for disease processes. The luminal surface of vascular endothelium throughout the body is covered with endothelial glycocalyx, comprising surface-anchored proteoglycans, supplemented with adsorbed soluble proteoglycans, glycosaminoglycans and plasma constituents. In both continuous and fenestrated microvessels, this endothelial glycocalyx provides resistance to the transcapillary escape of water and macromolecules, acting as an integral component of the multilayered barrier provided by the walls of these microvessels (ie acting in concert with clefts or fenestrae across endothelial cell layers, basement membranes and pericytes). Dysfunction of any of these capillary wall components, including the endothelial glycocalyx, can disrupt normal microvascular permeability. Because of its ubiquitous nature, damage to the endothelial glycocalyx alters the permeability of multiple capillary beds: in the glomerulus this is clinically apparent as albuminuria. Generalized damage to the endothelial glycocalyx can therefore manifest as both albuminuria and increased systemic microvascular permeability. This triad of altered endothelial glycocalyx, albuminuria and increased systemic microvascular permeability occurs in a number of important diseases, such as diabetes, with accumulating evidence for a similar phenomenon in ischaemia-reperfusion injury and infectious disease. The detection of albuminuria therefore has implications for the function of the microcirculation as a whole. The importance of the endothelial glycocalyx for other aspects of vascular function

The Deletion of Endothelial Sodium Channel α (αENaC Impairs Endothelium-Dependent Vasodilation and Endothelial Barrier Integrity in Endotoxemia in Vivo

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Magdalena Sternak

2018-04-01

Full Text Available The role of epithelial sodium channel (ENaC activity in the regulation of endothelial function is not clear. Here, we analyze the role of ENaC in the regulation of endothelium-dependent vasodilation and endothelial permeability in vivo in mice with conditional αENaC subunit gene inactivation in the endothelium (endo-αENaCKO mice using unique MRI-based analysis of acetylcholine-, flow-mediated dilation and vascular permeability. Mice were challenged or not with lipopolysaccharide (LPS, from Salmonella typhosa, 10 mg/kg, i.p.. In addition, changes in vascular permeability in ex vivo organs were analyzed by Evans Blue assay, while changes in vascular permeability in perfused mesenteric artery were determined by a FITC-dextran-based assay. In basal conditions, Ach-induced response was completely lost, flow-induced vasodilation was inhibited approximately by half but endothelial permeability was not changed in endo-αENaCKO vs. control mice. In LPS-treated mice, both Ach- and flow-induced vasodilation was more severely impaired in endo-αENaCKO vs. control mice. There was also a dramatic increase in permeability in lungs, brain and isolated vessels as evidenced by in vivo and ex vivo analysis in endotoxemic endo-αENaCKO vs. control mice. The impaired endothelial function in endotoxemia in endo-αENaCKO was associated with a decrease of lectin and CD31 endothelial staining in the lung as compared with control mice. In conclusion, the activity of endothelial ENaC in vivo contributes to endothelial-dependent vasodilation in the physiological conditions and the preservation of endothelial barrier integrity in endotoxemia.

Viability and proliferation of endothelial cells upon exposure to GaN nanoparticles.

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Braniste, Tudor; Tiginyanu, Ion; Horvath, Tibor; Raevschi, Simion; Cebotari, Serghei; Lux, Marco; Haverich, Axel; Hilfiker, Andres

2016-01-01

Nanotechnology is a rapidly growing and promising field of interest in medicine; however, nanoparticle-cell interactions are not yet fully understood. The goal of this work was to examine the interaction between endothelial cells and gallium nitride (GaN) semiconductor nanoparticles. Cellular viability, adhesion, proliferation, and uptake of nanoparticles by endothelial cells were investigated. The effect of free GaN nanoparticles versus the effect of growing endothelial cells on GaN functionalized surfaces was examined. To functionalize surfaces with GaN, GaN nanoparticles were synthesized on a sacrificial layer of zinc oxide (ZnO) nanoparticles using hydride vapor phase epitaxy. The uptake of GaN nanoparticles by porcine endothelial cells was strongly dependent upon whether they were fixed to the substrate surface or free floating in the medium. The endothelial cells grown on surfaces functionalized with GaN nanoparticles demonstrated excellent adhesion and proliferation, suggesting good biocompatibility of the nanostructured GaN.

Combined oral contraceptives: venous thrombosis.

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de Bastos, Marcos; Stegeman, Bernardine H; Rosendaal, Frits R; Van Hylckama Vlieg, Astrid; Helmerhorst, Frans M; Stijnen, Theo; Dekkers, Olaf M

2014-03-03

Combined oral contraceptive (COC) use has been associated with venous thrombosis (VT) (i.e., deep venous thrombosis and pulmonary embolism). The VT risk has been evaluated for many estrogen doses and progestagen types contained in COC but no comprehensive comparison involving commonly used COC is available. To provide a comprehensive overview of the risk of venous thrombosis in women using different combined oral contraceptives. Electronic databases (Pubmed, Embase, Web of Science, Cochrane, CINAHL, Academic Search Premier and ScienceDirect) were searched in 22 April 2013 for eligible studies, without language restrictions. We selected studies including healthy women taking COC with VT as outcome. The primary outcome of interest was a fatal or non-fatal first event of venous thrombosis with the main focus on deep venous thrombosis or pulmonary embolism. Publications with at least 10 events in total were eligible. The network meta-analysis was performed using an extension of frequentist random effects models for mixed multiple treatment comparisons. Unadjusted relative risks with 95% confidence intervals were reported.Two independent reviewers extracted data from selected studies. 3110 publications were retrieved through a search strategy; 25 publications reporting on 26 studies were included. Incidence of venous thrombosis in non-users from two included cohorts was 0.19 and 0.37 per 1 000 person years, in line with previously reported incidences of 0,16 per 1 000 person years. Use of combined oral contraceptives increased the risk of venous thrombosis compared with non-use (relative risk 3.5, 95% confidence interval 2.9 to 4.3). The relative risk of venous thrombosis for combined oral contraceptives with 30-35 μg ethinylestradiol and gestodene, desogestrel, cyproterone acetate, or drospirenone were similar and about 50-80% higher than for combined oral contraceptives with levonorgestrel. A dose related effect of ethinylestradiol was observed for gestodene

Percutaneous Placement of Central Venous Catheters: Comparing the Anatomical Landmark Method with the Radiologically Guided Technique for Central Venous Catheterization Through the Internal Jugular Vein in Emergent Hemodialysis Patients

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Koroglu, M.; Demir, M.; Koroglu, B.K.; Sezer, M.T.; Akhan, O.; Yildiz, H.; Yavuz, L.; Baykal, B.; Oyar, O. [Suleyman Demirel Univ., Isparta (Turkey). Depts. of Radiology, Internal Medicine and Anesthesiology

2006-02-15

Purpose: To compare the success and immediate complication rates of the anatomical landmark method (group 1) and the radiologically (combined real-time ultrasound and fluoroscopy) guided technique (group 2) in the placement of central venous catheters in emergent hemodialysis patients. Material and Methods: The study was performed prospectively in a randomized manner. The success and immediate complication rates of radiologically guided placement of central venous access catheters through the internal jugular vein (n = 40) were compared with those of the anatomical landmark method (n 40). The success of placement, the complications, the number of passes required, and whether a single or double-wall puncture occurred were also noted and compared. Results: The groups were comparable in age and sex. The indication for catheter placement was hemodialysis access in all patients. Catheter placement was successful in all patients in group 2 and unsuccessful in 1 (2.5%) patient in group 1. All catheters functioned adequately and immediately after the placement (0% initial failure rate) in group 2, but 3 catheters (7.5% initial failure rate) were non-functional just after placement in group 1. The total number of needle passes, double venous wall puncture, and complication rate were significantly lower in group 2. Conclusion: Percutaneous central venous catheterization via the internal jugular vein can be performed by interventional radiologists with better technical success rates and lower immediate complications. In conclusion, central venous catheterization for emergent dialysis should be performed under both real-time ultrasound and fluoroscopic guidance.

Venous chest anatomy: clinical implications

International Nuclear Information System (INIS)

Chasen, M.H.; Charnsangavej, C.

1998-01-01

This article provides a practical approach to the clinical implications and importance of understanding the collateral venous anatomy of the thorax. Routine radiography, conventional venography, computed tomography (CT), and magnetic resonance (MR) imaging studies provide correlative anatomic models for the demonstration of how interconnecting collateral vascular networks within the thorax maintain venous stability at all times. Five major systems comprise the collateral venous network of the thorax ( Fig. 1 ). These include the paravertebral, azygos-hemiazygos, internal mammary, lateral thoracic, and anterior jugular venous systems (AJVS). The five systems are presented in the following sequence: (a) a brief introduction to the importance of catheter position and malposition in understanding access to the thoracic venous system, (b) the anatomy of the azygos-hemiazygos systems and their relationship with the paravertebral plexus, (c) the importance of the AJVS, (d) 'loop' concepts interconnecting the internal mammary and azygos-hemiazygos systems by means of the lateral thoracic and intercostal veins, and (e) the interconnecting venous networks on the thoracic side of the thoracoabdominal junction. Certain aspects of the venous anatomy of the thorax will not be discussed in this chapter and include (a) the intra-abdominal anastomoses between the superior and inferior vena cavae (IVC) via the internal mammary, lateral thoracic, and azygos-hemiazygos systems (beyond the scope of this article), (b) potential collateral vessels involving vertebral, parascapular, thyroidal, thymic, and other smaller veins that might anastomose with the major systems, and (c) anatomic variants and pitfalls that may mimic pathologic conditions (space limitations). (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

Sonographic detection of portal venous gas

International Nuclear Information System (INIS)

Lee, Wang Yul; Lee, S. K.; Cho, O. K.

1989-01-01

Portal venous gas suggests underlying bowel disease such as strangulating intestinal obstruction and its demonstration carries with it an important implications with respect to patient management. Radiography has been the gold standard for the detection of portal venous gas. We have experienced two cases of portal venous gas diagnosed by ultrasound. Sonographic findings were floating echoes in the main portal vein and highly echogenic linear or patchy echoes within the hepatic parenchyma. Simple abdominal films of those cases failed to demonstrate gas in the portal venous system

Venous pump of the calf: a study of venous and muscular pressures.

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Alimi, Y S; Barthelemy, P; Juhan, C

1994-11-01

Little data are available concerning the relation between the muscular pumping mechanism and the variation of superficial and deep venous pressure during normal action of the calf pump; therefore we undertook this study to determine the pressure values in three compartments of the calf and in the deep and the superficial venous system and to establish correlation between muscular and venous pressure. Nine healthy young women with a mean age of 23 years (range 19 to 28 years) were examined. In the same calf, a muscular catheter was placed in the deep posterior compartment (DPC), in the superficial posterior compartment (SPC), and in the anterior tibial compartment (ATC), and a vascular catheter was placed in the popliteal vein and in the greater saphenous vein (GSV). The five lines of pressure were simultaneously recorded in the following situations: at rest, during Valsalva maneuver, foot flexion, and foot extension. The situation was studied with the patient in the following positions: decubitus, sitting, standing, and squatting. A final continuous recording was carried out after the patient had been walking for 5 minutes. Mean values with standard errors of muscular and venous pressure were established in each situation. At rest and during Valsalva maneuver, the muscular pressures did not vary, whereas venous pressures increased significantly when the patient was sitting and standing. On the other hand, squatting was associated with a rise in the muscular and vein pressures. Foot flexion entailed a significant increase in the ATC pressure and a rise in the GSV pressure, whereas foot extension caused the DPC pressure to rise without venous pressure modifications. Walking was associated with an alternating increase in the DPC, SPC, GSV and popliteal vein pressures when the foot was compressed to floor followed by a significant decrease when the foot pressure was released. The variations in the deep and superficial venous pressures when the patient is sitting and

Circulating endothelial cells as marker of endothelial damage in male hypogonadism.

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Milardi, Domenico; Grande, Giuseppe; Giampietro, Antonella; Vendittelli, Francesca; Palumbo, Sara; Tartaglione, Linda; Marana, Riccardo; Pontecorvi, Alfredo; de Marinis, Laura; Zuppi, Cecilia; Capoluongo, Ettore

2012-01-01

Testosterone deficiency has become a frequently diagnosed condition in today's society affected by epidemic obesity, and is associated with cardiovascular risk. Recent studies have established the importance of altered vascular endothelium function in cardiovascular disease. The damage to the endothelium might also cause endothelial cell detachment, resulting in increased numbers of circulating endothelial cells (CEC) within the bloodstream. To evaluate whether hypogonadism could modify CEC count in peripheral bloodstream, we investigated peripheral blood CEC count using the CellSearch System, a semiautomatic method to accurately and reliably enumerate CECs, which are sorted based on a CD146(+), CD105(+), DAPI(+), CD45(-) phenotype, in a population of 20 patients with hypogonadism. The control group comprised 10 age- and sex-matched healthy participants. CEC count per milliliter was significantly increased in patients with hypogonadism vs the control group. In the group with hypogonadism, an inverse exponential correlation was present between testosterone levels and CEC count per milliliter. A direct linear correlation was present between waist circumference and CECs and between body mass index and CECs. The regression analysis showed that testosterone was the significant independent determinant of CECs. Our results underline that male hypogonadism is associated with endothelial dysfunction. The correlation between CEC and waist circumference underlines that visceral obesity may be synergically implicated in this regulation. Future studies are required to unveil the mechanisms involved in the pathogenesis of testosterone-induced endothelial disfunction, which may provide novel therapeutic targets to be incorporated in the management of hypogonadism.

A new approach to improve the specificity of flow-mediated dilation for indicating endothelial function in cardiovascular research.

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Atkinson, Greg; Batterham, Alan M; Thijssen, Dick H J; Green, Daniel J

2013-02-01

Flow-mediated dilation (FMD) is a noninvasive indicator of endothelial function and is routinely expressed as the percentage change in arterial diameter (FMD%) from a resting baseline (Dbase) to a postischemic peak (Dpeak). This expression is equivalent to the ratio of Dpeak/Dbase and is, therefore, dependent on important statistical assumptions, which have never been analysed in the context of FMD%. We aimed to investigate these assumptions, via a comparison of FMD between samples of children and adults, as well as to explore other approaches to scaling diameter change for Dbase. We found that FMD% did not scale accurately for interindividual differences in Dbase but, as expected, overestimated endothelial function for low Dbase and vice versa. We argue that this imprecise scaling of FMD% is predictable, not explained by physiology and is probably common. This problem is resolved by applying scaling principles, whereby the difference in diameter is the outcome and Dbase is a covariate in a logarithmic-linked generalized linear model. A specific allometric expression of FMD can be derived and we found this to be Dpeak/Dbase rather than a simple ratio in our particular dataset. We found that sample differences in endothelial function were inaccurate with FMD% versus our new allometric approach, and that FMD% misclassified participants into 'high' and 'low'cohorts, which has implications for prognostic-type studies. We conclude that the general use of FMD% could have led to biased comparisons of different conditions and/or populations in past studies. Our new approach to scaling FMD is flexible for different datasets and is not based on the current assumption that a percentage change is appropriate in all circumstances.

Endothelial disruptive proinflammatory effects of nicotine and e-cigarette vapor exposures.

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Schweitzer, Kelly S; Chen, Steven X; Law, Sarah; Van Demark, Mary; Poirier, Christophe; Justice, Matthew J; Hubbard, Walter C; Kim, Elena S; Lai, Xianyin; Wang, Mu; Kranz, William D; Carroll, Clinton J; Ray, Bruce D; Bittman, Robert; Goodpaster, John; Petrache, Irina

2015-07-15

The increased use of inhaled nicotine via e-cigarettes has unknown risks to lung health. Having previously shown that cigarette smoke (CS) extract disrupts the lung microvasculature barrier function by endothelial cell activation and cytoskeletal rearrangement, we investigated the contribution of nicotine in CS or e-cigarettes (e-Cig) to lung endothelial injury. Primary lung microvascular endothelial cells were exposed to nicotine, e-Cig solution, or condensed e-Cig vapor (1-20 mM nicotine) or to nicotine-free CS extract or e-Cig solutions. Compared with nicotine-containing extract, nicotine free-CS extract (10-20%) caused significantly less endothelial permeability as measured with electric cell-substrate impedance sensing. Nicotine exposures triggered dose-dependent loss of endothelial barrier in cultured cell monolayers and rapidly increased lung inflammation and oxidative stress in mice. The endothelial barrier disruptive effects were associated with increased intracellular ceramides, p38 MAPK activation, and myosin light chain (MLC) phosphorylation, and was critically mediated by Rho-activated kinase via inhibition of MLC-phosphatase unit MYPT1. Although nicotine at sufficient concentrations to cause endothelial barrier loss did not trigger cell necrosis, it markedly inhibited cell proliferation. Augmentation of sphingosine-1-phosphate (S1P) signaling via S1P1 improved both endothelial cell proliferation and barrier function during nicotine exposures. Nicotine-independent effects of e-Cig solutions were noted, which may be attributable to acrolein, detected along with propylene glycol, glycerol, and nicotine by NMR, mass spectrometry, and gas chromatography, in both e-Cig solutions and vapor. These results suggest that soluble components of e-Cig, including nicotine, cause dose-dependent loss of lung endothelial barrier function, which is associated with oxidative stress and brisk inflammation.

Evaluation of factor for one-point venous blood sampling method based on the causality model

International Nuclear Information System (INIS)

Matsutomo, Norikazu; Onishi, Hideo; Kobara, Kouichi; Sasaki, Fumie; Watanabe, Haruo; Nagaki, Akio; Mimura, Hiroaki

2009-01-01

One-point venous blood sampling method (Mimura, et al.) can evaluate the regional cerebral blood flow (rCBF) value with a high degree of accuracy. However, the method is accompanied by complexity of technique because it requires a venous blood Octanol value, and its accuracy is affected by factors of input function. Therefore, we evaluated the factors that are used for input function to determine the accuracy input function and simplify the technique. The input function which uses the time-dependent brain count of 5 minutes, 15 minutes, and 25 minutes from administration, and the input function in which an objective variable is used as the artery octanol value to exclude the venous blood octanol value are created. Therefore, a correlation between these functions and rCBF value by the microsphere (MS) method is evaluated. Creation of a high-accuracy input function and simplification of technique are possible. The rCBF value obtained by the input function, the factor of which is a time-dependent brain count of 5 minutes from administration, and the objective variable is artery octanol value, had a high correlation with the MS method (y=0.899x+4.653, r=0.842). (author)

Evaluation of hepatic venous pulsatility and portal venous velocity with doppler ultrasonography during the puerperium

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Pekindil, Goekhan [Department of Radiology, Trakya University School of Medicine, 22030 Edirne (Turkey); Varol, Fuesun G. [Department of Obstetrics and Gynecology, Trakya University School of Medicine, 22030 Edirne (Turkey); Ali Yuece, M. [Department of Obstetrics and Gynecology, Trakya University School of Medicine, 22030 Edirne (Turkey); Yardim, Turgut [Department of Obstetrics and Gynecology, Trakya University School of Medicine, 22030 Edirne (Turkey)

1999-03-01

Objective: The aim of this study is to evaluate pregnancy-induced changes of hepatic venous pulsatility and portal venous velocity in the puerperium and to determine if these changes disappeared by the end of the puerperium. Methods and material: Healthy normal volunteers (90) were examined on the 2nd and 7th days of puerperium and between the 6th and 8th weeks postpartum. Doppler waveform patterns were obtained in the middle hepatic vein and main portal vein. The hepatic venous pulsatility was named as normal, damped or flat. Results: On the 2nd day postpartum, the hepatic vein pulsatility was shown as normal in 8 (26%), damped in 11 (37%) and flat in 11 (37%) cases. On the 7th day postpartum, 15 (50%) cases had normal, 9 (30%) cases had dampened, and 6 (20%) cases had still flat pattern. The majority of the cases (60%) displayed normal hepatic venous pulsatility in the 6th and 8th weeks of puerperium, whereas 23% had still dampened and 17% had flat patterns. There was a trend toward normal pulsatility with increasing puerperal age. The mean portal venous velocity was still higher than the non-pregnant levels and did not showed significant alterations during puerperium. Conclusion: This study emphasised that, since pregnancy-induced alterations in hepatic venous pulsatility and portal venous velocity had not completely returned to normal in most cases until the end of the puerperium, these physiological changes should be considered whenever hepatic and portal systems are interpreted with Doppler sonography during the puerperal period.

Evaluation of hepatic venous pulsatility and portal venous velocity with doppler ultrasonography during the puerperium

International Nuclear Information System (INIS)

Pekindil, Goekhan; Varol, Fuesun G.; Ali Yuece, M.; Yardim, Turgut

1999-01-01

Objective: The aim of this study is to evaluate pregnancy-induced changes of hepatic venous pulsatility and portal venous velocity in the puerperium and to determine if these changes disappeared by the end of the puerperium. Methods and material: Healthy normal volunteers (90) were examined on the 2nd and 7th days of puerperium and between the 6th and 8th weeks postpartum. Doppler waveform patterns were obtained in the middle hepatic vein and main portal vein. The hepatic venous pulsatility was named as normal, damped or flat. Results: On the 2nd day postpartum, the hepatic vein pulsatility was shown as normal in 8 (26%), damped in 11 (37%) and flat in 11 (37%) cases. On the 7th day postpartum, 15 (50%) cases had normal, 9 (30%) cases had dampened, and 6 (20%) cases had still flat pattern. The majority of the cases (60%) displayed normal hepatic venous pulsatility in the 6th and 8th weeks of puerperium, whereas 23% had still dampened and 17% had flat patterns. There was a trend toward normal pulsatility with increasing puerperal age. The mean portal venous velocity was still higher than the non-pregnant levels and did not showed significant alterations during puerperium. Conclusion: This study emphasised that, since pregnancy-induced alterations in hepatic venous pulsatility and portal venous velocity had not completely returned to normal in most cases until the end of the puerperium, these physiological changes should be considered whenever hepatic and portal systems are interpreted with Doppler sonography during the puerperal period

Functional Differences Between Placental Micro- and Macrovascular Endothelial Colony-Forming Cells

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Solomon, Ioana; O’Reilly, Megan; Ionescu, Lavinia; Alphonse, Rajesh S.; Rajabali, Saima; Zhong, Shumei; Vadivel, Arul; Shelley, W. Chris; Yoder, Mervin C.

2016-01-01

Alterations in the development of the placental vasculature can lead to pregnancy complications, such as preeclampsia. Currently, the cause of preeclampsia is unknown, and there are no specific prevention or treatment strategies. Further insight into the placental vasculature may aid in identifying causal factors. Endothelial colony-forming cells (ECFCs) are a subset of endothelial progenitor cells capable of self-renewal and de novo vessel formation in vitro. We hypothesized that ECFCs exist in the micro- and macrovasculature of the normal, term human placenta. Human placentas were collected from term pregnancies delivered by cesarean section (n = 16). Placental micro- and macrovasculature was collected from the maternal and fetal side of the placenta, respectively, and ECFCs were isolated and characterized. ECFCs were CD31+, CD105+, CD144+, CD146+, CD14−, and CD45−, took up 1,1′-dioctadecyl-3,3,3′,3′-tetramethyl-indocarbocyanine perchlorate-labeled acetylated low-density lipoprotein, and bound Ulex europaeus agglutinin 1. In vitro, macrovascular ECFCs had a greater potential to generate high-proliferative colonies and formed more complex capillary-like networks on Matrigel compared with microvascular ECFCs. In contrast, in vivo assessment demonstrated that microvascular ECFCs had a greater potential to form vessels. Macrovascular ECFCs were of fetal origin, whereas microvascular ECFCs were of maternal origin. ECFCs exist in the micro- and macrovasculature of the normal, term human placenta. Although macrovascular ECFCs demonstrated greater vessel and colony-forming potency in vitro, this did not translate in vivo, where microvascular ECFCs exhibited a greater vessel-forming ability. These important findings contribute to the current understanding of normal placental vascular development and may aid in identifying factors involved in preeclampsia and other pregnancy complications. Significance This research confirms that resident endothelial colony

RhoA GTPase regulates radiation-induced alterations in endothelial cell adhesion and migration

International Nuclear Information System (INIS)

Rousseau, Matthieu; Gaugler, Marie-Hélène; Rodallec, Audrey; Bonnaud, Stéphanie; Paris, François; Corre, Isabelle

2011-01-01

Highlights: ► We explore the role of RhoA in endothelial cell response to ionizing radiation. ► RhoA is rapidly activated by single high-dose of radiation. ► Radiation leads to RhoA/ROCK-dependent actin cytoskeleton remodeling. ► Radiation-induced apoptosis does not require the RhoA/ROCK pathway. ► Radiation-induced alteration of endothelial adhesion and migration requires RhoA/ROCK. -- Abstract: Endothelial cells of the microvasculature are major target of ionizing radiation, responsible of the radiation-induced vascular early dysfunctions. Molecular signaling pathways involved in endothelial responses to ionizing radiation, despite being increasingly investigated, still need precise characterization. Small GTPase RhoA and its effector ROCK are crucial signaling molecules involved in many endothelial cellular functions. Recent studies identified implication of RhoA/ROCK in radiation-induced increase in endothelial permeability but other endothelial functions altered by radiation might also require RhoA proteins. Human microvascular endothelial cells HMEC-1, either treated with Y-27632 (inhibitor of ROCK) or invalidated for RhoA by RNA interference were exposed to 15 Gy. We showed a rapid radiation-induced activation of RhoA, leading to a deep reorganisation of actin cytoskeleton with rapid formation of stress fibers. Endothelial early apoptosis induced by ionizing radiation was not affected by Y-27632 pre-treatment or RhoA depletion. Endothelial adhesion to fibronectin and formation of focal adhesions increased in response to radiation in a RhoA/ROCK-dependent manner. Consistent with its pro-adhesive role, ionizing radiation also decreased endothelial cells migration and RhoA was required for this inhibition. These results highlight the role of RhoA GTPase in ionizing radiation-induced deregulation of essential endothelial functions linked to actin cytoskeleton.

Effects of Acute Active Video Games on Endothelial Function Following a High-Fat Meal in Overweight Adolescents.

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Park, Soo Hyun; Yoon, Eun Sun; Lee, Yong Hee; Kim, Chul-Ho; Bunsawat, Kanokwan; Heffernan, Kevin S; Fernall, Bo; Jae, Sae Young

2015-06-01

We tested the hypothesis that an active video game following a high-fat meal would partially prevent the unfavorable effect of a high-fat meal on vascular function in overweight adolescents. Twenty-four overweight adolescents were randomized to either a 60-minute active video game (AVG) group (n = 12) or seated rest (SR) as a control group (n = 12) after a high-fat meal. Blood parameters were measured, and vascular function was measured using brachial artery flow-mediated dilation (FMD) at baseline and 3 hours after a high-fat meal. No significant interaction was found in any blood parameter. A high-fat meal significantly increased blood triglyceride and glucose concentrations in both groups in a similar manner. Brachial artery FMD significantly decreased in the SR group (13.8 ± 3.2% to 11.8 ± 2.5), but increased in the AVG group (11.4 ± 4.0% to 13.3 ± 3.5), with a significant interaction (P = .034). These findings show that an active video game attenuated high-fat meal-induced endothelial dysfunction. This suggests that an active video game may have a cardioprotective effect on endothelial function in overweight adolescents when exposed to a high-fat meal.

[An update on the treatment of venous insufficiency in pregnancy].

Science.gov (United States)

Rodríguez-Nora, B; Álvarez-Silvares, E

Chronic venous insufficiency is a long-term pathological condition resulting from anatomical or functional alterations of the venous system. This leads to the appearance of symptoms and physical signs that affect a large part of the population and particularly pregnant women, due to the physiology of pregnancy. The few published studies on the use of pharmacological treatments of venous insufficiency in this group of the population, often makes the management of this condition difficult in routine clinical practice. A review is presented in this article, with all the latest updates in the treatment of this condition during pregnancy. There are numerous general, and some pharmacological, recommendations, that we can safely offer the pregnant patient. Copyright © 2017 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Morpho-functional characterization of the systemic venous pole of the reptile heart

NARCIS (Netherlands)

Jensen, Bjarke; Vesterskov, Signe; Boukens, Bastiaan J.; Nielsen, Jan M.; Moorman, Antoon F. M.; Christoffels, Vincent M.; Wang, Tobias

2017-01-01

Mammals evolved from reptile-like ancestors, and while the mammalian heart is driven by a distinct sinus node, a sinus node is not apparent in reptiles. We characterized the myocardial systemic venous pole, the sinus venosus, in reptiles to identify the dominant pacemaker and to assess whether the

Changes in endothelial function, arterial stiffness and blood pressure in pregnant women after consumption of high-flavanol and high-theobromine chocolate: a double blind randomized clinical trial.

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Babar, Asma; Bujold, Emmanuel; Leblanc, Vicky; Lavoie-Lebel, Élise; Paquette, Joalee; Bazinet, Laurent; Lemieux, Simone; Marc, Isabelle; Abdous, Belkacem; Dodin, Sylvie

2018-04-16

The aim of this 2-group, parallel, double blind single-centre RCT was to evaluate the acute and chronic impacts of high flavanol high theobromine (HFHT) chocolate consumption on endothelial function, arterial stiffness and blood pressure (BP) in women at risk of preeclampsia. 131 pregnant women considered at risk of preeclampsia based on uterine artery Doppler ultrasound were divided into two groups (HFHT or low flavanol and theobromine chocolate (LFLT). Acute changes in plasma flavanol and theobromine, peripheral arterial tonometry and BP were evaluated at randomization (0, 60 and 120 min after a single 40-g dose of chocolate) and again 6 and 12 weeks after daily 30-g chocolate intake. The EndoPAT 2000 provided reactive hyperemia index (RHI) and adjusted augmentation index (AIx) as markers for endothelial function and arterial stiffness, respectively. Compared with LFLT, acute HFHT intake significantly increased plasma epicatechin and theobromine (p theobromine (p theobromine concentrations and decreased arterial stiffness, with no effect on endothelial function and a marginal increase in diastolic BP. Chronic HFHT intake increased plasma theobromine, though it did not have positive impacts on endothelial function, arterial stiffness or BP when compared to LFLT in pregnant women at risk of PE.

Endothelium-dependent vasodilatation, plasma markers of endothelial function, and adrenergic vasoconstrictor responses in type 1 diabetes under near-normoglycemic conditions

NARCIS (Netherlands)

Huvers, F C; De Leeuw, P W; Houben, A J; De Haan, C H; Hamulyak, K; Schouten, H; Wolffenbuttel, B H; Schaper, N C

It is unknown whether and to what extent changes in various endothelial functions and adrenergic responsiveness are related to the development of microvascular complications in type 1 diabetes. Therefore, endothelium-dependent and endothelium-independent vasodilatation, endothelium-dependent

Expression of Vascular Endothelial Growth Factor Receptors in Benign Vascular Lesions of the Orbit: A Case Series.

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Atchison, Elizabeth A; Garrity, James A; Castillo, Francisco; Engman, Steven J; Couch, Steven M; Salomão, Diva R

2016-01-01

Vascular lesions of the orbit, although not malignant, can cause morbidity because of their location near critical structures in the orbit. For the same reason, they can be challenging to remove surgically. Anti-vascular endothelial growth factor (VEGF) drugs are increasingly being used to treat diseases with prominent angiogenesis. Our study aimed to determine to what extent VEGF receptors and their subtypes are expressed on selected vascular lesions of the orbit. Retrospective case series of all orbital vascular lesions removed by one of the authors (JAG) at the Mayo Clinic. A total of 52 patients who underwent removal of vascular orbital lesions. The pathology specimens from the patients were retrieved, their pathologic diagnosis was confirmed, demographic and clinical information were gathered, and sections from vascular tumors were stained with vascular endothelial growth factor receptor (VEGFR), vascular endothelial growth factor receptor type 1 (VEGFR1), vascular endothelial growth factor receptor type 2 (VEGFR2), and vascular endothelial growth factor receptor type 3 (VEGFR3). The existence and pattern of staining with VEGF and its subtypes on these lesions. There were 28 specimens of venous malformations, 4 capillary hemangiomas, 7 lymphatic malformations, and 6 lymphaticovenous malformations. All samples stained with VEGF, 55% stained with VEGFR1, 98% stained with VEGFR2, and 96% stained with VEGFR3. Most (94%) of the VEGFR2 staining was diffuse. Most orbital vascular lesions express VEGF receptors, which may suggest a future target for nonsurgical treatment. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

A Novel Stretch Sensor to Measure Venous Hemodynamics

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Syrpailyne Wankhar

2018-07-01

Full Text Available Chronic venous insufficiency is a debilitating condition causing varicose veins and venous ulcers. The pathophysiology includes reflux and venous obstruction. The diagnosis is often made by clinical examination and confirmed by Venous Doppler studies. Plethysmography helps to quantitatively examine the reflux and diagnose the burden of deep venous pathology to better understand venous hemodynamics, which is not elicited by venous duplex examination alone. However, most of these tests are qualitative, expensive, and not easily available. In this paper, we demonstrate the potential use of a novel stretch sensor in the assessment of venous hemodynamics during different maneuvers by measuring the change in calf circumference. We designed the stretch sensor by using semiconductor strain gauges pasted onto a small metal bar to form a load cell. The elastic and Velcro material attached to the load cell form a belt. It converts the change in limb circumference to a proportional tension (force of distension when placed around the calf muscle. We recorded the change in limb circumference from arrays of stretch sensors by using an in-house data acquisition system. We calculated the venous volume (VV, venous filling index (VFI, ejection fraction (EF and residual venous volume (RVV on two normal subjects and on two patients to assess venous hemodynamics. The values (VV > 60 ml, VFI 60%, RVV 2ml/s, EF 35% in patients were comparable to those reported in the literature.

Role of glutathione biosynthesis in endothelial dysfunction and fibrosis.

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Espinosa-Díez, Cristina; Miguel, Verónica; Vallejo, Susana; Sánchez, Francisco J; Sandoval, Elena; Blanco, Eva; Cannata, Pablo; Peiró, Concepción; Sánchez-Ferrer, Carlos F; Lamas, Santiago

2018-04-01

Glutathione (GSH) biosynthesis is essential for cellular redox homeostasis and antioxidant defense. The rate-limiting step requires glutamate-cysteine ligase (GCL), which is composed of the catalytic (GCLc) and the modulatory (GCLm) subunits. To evaluate the contribution of GCLc to endothelial function we generated an endothelial-specific Gclc haplo-insufficient mouse model (Gclc e/+ mice). In murine lung endothelial cells (MLEC) derived from these mice we observed a 50% reduction in GCLc levels compared to lung fibroblasts from the same mice. MLEC obtained from haplo-insufficient mice showed significant reduction in GSH levels as well as increased basal and stimulated ROS levels, reduced phosphorylation of eNOS (Ser 1177) and increased eNOS S-glutathionylation, compared to MLEC from wild type (WT) mice. Studies in mesenteric arteries demonstrated impaired endothelium-dependent vasodilation in Gclc(e/+) male mice, which was corrected by pre-incubation with GSH-ethyl-ester and BH 4 . To study the contribution of endothelial GSH synthesis to renal fibrosis we employed the unilateral ureteral obstruction model in WT and Gclc(e/+) mice. We observed that obstructed kidneys from Gclc(e/+) mice exhibited increased deposition of fibrotic markers and reduced Nrf2 levels. We conclude that the preservation of endothelial GSH biosynthesis is not only critical for endothelial function but also in anti-fibrotic responses. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

PECAM-1 polymorphism affects monocyte adhesion to endothelial cells.

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Goodman, Reyna S; Kirton, Christopher M; Oostingh, Gertie J; Schön, Michael P; Clark, Michael R; Bradley, J Andrew; Taylor, Craig J

2008-02-15

Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) plays an important role in leukocyte-endothelial cell adhesion and transmigration. Single nucleotide polymorphisms of PECAM-1 encoding amino acid substitutions at positions 98 leucine/valine (L/V), 536 serine/asparagine (S/N), and 643 arginine/glycine (R/G) occur in strong genetic linkage resulting in two common haplotypes (LSR and VNG). These PECAM-1 polymorphisms are associated with graft-versus-host disease after hematopoietic stem cell transplantation and with cardiovascular disease, but whether they influence PECAM-1 function is unknown. We examined the effect of homozygous and heterozygous expression of the PECAM-1 LSR and VNG genotypes on the adhesive interactions of peripheral blood monocytes and activated endothelial cell monolayers under shear stress in a flow-based cell adhesion assay. There was no difference in monocyte adhesion between the two homozygous genotypes of PECAM-1 but when monocytes expressed both alleles in heterozygous form, firm adhesion of monocytes to endothelial cells was markedly increased. PECAM-1 polymorphism expressed in homozygous or heterozygous form by endothelial cells did not influence monocyte adhesion. This is, to our knowledge, the first demonstration that PECAM-1 genotype can alter the level of monocyte binding to endothelial cells and a demonstration that heterozygous expression of a polymorphic protein may lead to altered function.

Advanced glycation end products impair function of late endothelial progenitor cells through effects on protein kinase Akt and cyclooxygenase-2

International Nuclear Information System (INIS)

Chen Qin; Dong Li; Wang Lian; Kang Lina; Xu Biao

2009-01-01

Endothelial progenitor cells (EPCs) exhibit impaired function in the context of diabetes, and advanced glycation end products (AGEs), which accumulate in diabetes, may contribute to this. In the present study, we investigated the mechanism by which AGEs impair late EPC function. EPCs from human umbilical cord blood were isolated, and incubated with AGE-modified albumin (AGE-albumin) at different concentrations found physiologically in plasma. Apoptosis, migration, and tube formation assays were used to evaluate EPC function including capacity for vasculogenesis, and expression of the receptor for AGEs (RAGE), Akt, endothelial nitric oxide synthase (eNOS), and cycloxygenase-2 (COX-2) were determined. Anti-RAGE antibody was used to block RAGE function. AGE-albumin concentration-dependently enhanced apoptosis and depressed migration and tube formation, but did not affect proliferation, of late EPCs. High AGE-albumin increased RAGE mRNA and protein expression, and decreased Akt and COX-2 protein expression, whilst having no effect on eNOS mRNA or protein in these cells. These effects were inhibited by co-incubation with anti-RAGE antibody. These results suggest that RAGE mediates the AGE-induced impairment of late EPC function, through down-regulation of Akt and COX-2 in these cells.

Impedance analysis of GPCR-mediated changes in endothelial barrier function: overview and fundamental considerations for stable and reproducible measurements.

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Stolwijk, Judith A; Matrougui, Khalid; Renken, Christian W; Trebak, Mohamed

2015-10-01

The past 20 years has seen significant growth in using impedance-based assays to understand the molecular underpinning of endothelial and epithelial barrier function in response to physiological agonists and pharmacological and toxicological compounds. Most studies on barrier function use G protein-coupled receptor (GPCR) agonists which couple to fast and transient changes in barrier properties. The power of impedance-based techniques such as electric cell-substrate impedance sensing (ECIS) resides in its ability to detect minute changes in cell layer integrity label-free and in real-time ranging from seconds to days. We provide a comprehensive overview of the biophysical principles, applications, and recent developments in impedance-based methodologies. Despite extensive application of impedance analysis in endothelial barrier research, little attention has been paid to data analysis and critical experimental variables, which are both essential for signal stability and reproducibility. We describe the rationale behind common ECIS data presentation and interpretation and illustrate practical guidelines to improve signal intensity by adapting technical parameters such as electrode layout, monitoring frequency, or parameter (resistance versus impedance magnitude). Moreover, we discuss the impact of experimental parameters, including cell source, liquid handling, and agonist preparation on signal intensity and kinetics. Our discussions are supported by experimental data obtained from human microvascular endothelial cells challenged with three GPCR agonists, thrombin, histamine, and sphingosine-1-phosphate.

Topographic characteristics after Descemet's membrane endothelial keratoplasty and Descemet's stripping automated endothelial keratoplasty.

Directory of Open Access Journals (Sweden)

Takahiko Hayashi

Full Text Available To investigate the topographic characteristics of the posterior corneal surface after Descemet's endothelial membrane keratoplasty (DMEK and Descemet's stripping automated endothelial keratoplasty (DSAEK and their effects on postoperative visual acuity.Nineteen eyes of 19 patients after DMEK, 23 eyes of 23 patients after DSAEK, and 18 eyes of 18 control subjects were retrospectively analyzed. Best spectacle-corrected visual acuity (BSCVA, aberration factors (higher-order aberrations [HOAs], spherical aberrations [SAs], and coma aberrations [Comas] at 6.0 mm were evaluated preoperatively and at 1, 3, and 6 months postoperatively. The posterior refractive pattern of the topography map was classified into 5 grades (0-5 (posterior color grade using anterior segment optical coherence tomography. Correlations between BSCVA and some factors (abbreviation factors, posterior color grade were analyzed.BSCVA was significantly better after DMEK than after DSAEK (P < 0.001. Posterior HOAs, SAs, and Comas after each type of endothelial keratoplasty were significantly greater compared to control (P < 0.01. Posterior HOAs, total/anterior/posterior SAs, and posterior color grade were significantly lower in the DMEK group than in the DSAEK group at 3 months (P < 0.024 [posterior HOAs], P = 0.047 [total SA], P < 0.001 [anterior SAs], P = 0.021 [posterior SAs], and P < 0.001 [posterior color grade] and 6 months postoperatively (P = 0.034 [posterior HOAs], P < 0.001 [total SAs], P < 0.001 [anterior SAs], P = 0.013 [posterior SAs], and P = 0.004 [posterior color grade]. BSCVA was significantly correlated with HOAs, SAs, and posterior color grade (P < 0.001 for all except anterior HOAs [P = 0.004].High posterior color grades were associated with larger aberration factors and had a negative effect on visual function after endothelial keratoplasty. Rapid improvement of visual function after DMEK may be attributed to less change at the posterior surface.

Endothelial dysfunction: a comprehensive appraisal

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Vilariño Jorge O

2006-02-01

Full Text Available Abstract The endothelium is a thin monocelular layer that covers all the inner surface of the blood vessels, separating the circulating blood from the tissues. It is not an inactive organ, quite the opposite. It works as a receptor-efector organ and responds to each physical or chemical stimulus with the release of the correct substance with which it may maintain vasomotor balance and vascular-tissue homeostasis. It has the property of producing, independently, both agonistic and antagonistic substances that help to keep homeostasis and its function is not only autocrine, but also paracrine and endocrine. In this way it modulates the vascular smooth muscle cells producing relaxation or contraction, and therefore vasodilatation or vasoconstriction. The endothelium regulating homeostasis by controlling the production of prothrombotic and antithrombotic components, and fibrynolitics and antifibrynolitics. Also intervenes in cell proliferation and migration, in leukocyte adhesion and activation and in immunological and inflammatory processes. Cardiovascular risk factors cause oxidative stress that alters the endothelial cells capacity and leads to the so called endothelial "dysfunction" reducing its capacity to maintain homeostasis and leads to the development of pathological inflammatory processes and vascular disease. There are different techniques to evaluate the endothelium functional capacity, that depend on the amount of NO produced and the vasodilatation effect. The percentage of vasodilatation with respect to the basal value represents the endothelial functional capacity. Taking into account that shear stress is one of the most important stimulants for the synthesis and release of NO, the non-invasive technique most often used is the transient flow-modulate "endothelium-dependent" post-ischemic vasodilatation, performed on conductance arteries such as the brachial, radial or femoral arteries. This vasodilatation is compared with the

Endothelial progenitor cells in chronic obstructive pulmonary disease and emphysema

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Tracy, Russell P.; Parikh, Megha A.; Hoffman, Eric A.; Shimbo, Daichi; Austin, John H. M.; Smith, Benjamin M.; Hueper, Katja; Vogel-Claussen, Jens; Lima, Joao; Gomes, Antoinette; Watson, Karol; Kawut, Steven; Barr, R. Graham

2017-01-01

Endothelial injury is implicated in the pathogenesis of COPD and emphysema; however the role of endothelial progenitor cells (EPCs), a marker of endothelial cell repair, and circulating endothelial cells (CECs), a marker of endothelial cell injury, in COPD and its subphenotypes is unresolved. We hypothesized that endothelial progenitor cell populations would be decreased in COPD and emphysema and that circulating endothelial cells would be increased. Associations with other subphenotypes were examined. The Multi-Ethnic Study of Atherosclerosis COPD Study recruited smokers with COPD and controls age 50–79 years without clinical cardiovascular disease. Endothelial progenitor cell populations (CD34+KDR+ and CD34+KDR+CD133+ cells) and circulating endothelial cells (CD45dimCD31+CD146+CD133-) were measured by flow cytometry. COPD was defined by standard spirometric criteria. Emphysema was assessed qualitatively and quantitatively on CT. Full pulmonary function testing and expiratory CTs were measured in a subset. Among 257 participants, both endothelial progenitor cell populations, and particularly CD34+KDR+ endothelial progenitor cells, were reduced in COPD. The CD34+KDR+CD133+ endothelial progenitor cells were associated inversely with emphysema extent. Both endothelial progenitor cell populations were associated inversely with extent of panlobular emphysema and positively with diffusing capacity. Circulating endothelial cells were not significantly altered in COPD but were inversely associated with pulmonary microvascular blood flow on MRI. There was no consistent association of endothelial progenitor cells or circulating endothelial cells with measures of gas trapping. These data provide evidence that endothelial repair is impaired in COPD and suggest that this pathological process is specific to emphysema. PMID:28291826

The adaptor CRADD/RAIDD controls activation of endothelial cells by proinflammatory stimuli.

Science.gov (United States)

Qiao, Huan; Liu, Yan; Veach, Ruth A; Wylezinski, Lukasz; Hawiger, Jacek

2014-08-08

A hallmark of inflammation, increased vascular permeability, is induced in endothelial cells by multiple agonists through stimulus-coupled assembly of the CARMA3 signalosome, which contains the adaptor protein BCL10. Previously, we reported that BCL10 in immune cells is targeted by the "death" adaptor CRADD/RAIDD (CRADD), which negatively regulates nuclear factor κB (NFκB)-dependent cytokine and chemokine expression in T cells (Lin, Q., Liu, Y., Moore, D. J., Elizer, S. K., Veach, R. A., Hawiger, J., and Ruley, H. E. (2012) J. Immunol. 188, 2493-2497). This novel anti-inflammatory CRADD-BCL10 axis prompted us to analyze CRADD expression and its potential anti-inflammatory action in non-immune cells. We focused our study on microvascular endothelial cells because they play a key role in inflammation. We found that CRADD-deficient murine endothelial cells display heightened BCL10-mediated expression of the pleotropic proinflammatory cytokine IL-6 and chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2) in response to LPS and thrombin. Moreover, these agonists also induce significantly increased permeability in cradd(-/-), as compared with cradd(+/+), primary murine endothelial cells. CRADD-deficient cells displayed more F-actin polymerization with concomitant disruption of adherens junctions. In turn, increasing intracellular CRADD by delivery of a novel recombinant cell-penetrating CRADD protein (CP-CRADD) restored endothelial barrier function and suppressed the induction of IL-6 and MCP-1 evoked by LPS and thrombin. Likewise, CP-CRADD enhanced barrier function in CRADD-sufficient endothelial cells. These results indicate that depletion of endogenous CRADD compromises endothelial barrier function in response to inflammatory signals. Thus, we define a novel function for CRADD in endothelial cells as an inducible suppressor of BCL10, a key mediator of responses to proinflammatory agonists. © 2014 by The American Society for Biochemistry and Molecular Biology

Improved endothelial cell seeding with cultured cells and fibronectin-coated grafts