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Sample records for normal endothelial function

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

    Science.gov (United States)

    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

  2. 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...

  3. 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...

  4. Increased Rho-kinase expression and activity and pulmonary endothelial dysfunction in smokers with normal lung function.

    Science.gov (United States)

    Duong-Quy, S; Dao, P; Hua-Huy, T; Guilluy, C; Pacaud, P; Dinh-Xuan, A T

    2011-02-01

    Endothelial dysfunction is one of the main consequences of the toxic effects of cigarette smoke on the vascular system. Increasing evidence suggests that the small G-protein RhoA and its downstream effectors, the Rho-kinases (ROCKs), are involved in systemic endothelial dysfunction induced by cigarette smoke. This study aimed to evaluate the role of the RhoA/ROCKs pathway in pulmonary artery endothelial function in current smokers with normal lung function. Lung tissues were obtained from nonsmokers and smokers who underwent lobectomy for lung carcinoma. Arterial relaxation in response to acetylcholine (ACh) was assessed in isolated pulmonary arterial rings. Protein expressions and activities of endothelial nitric oxide synthase (eNOS), ROCKs and the myosin phosphatase subunit 1 (MYPT-1) were sought. Relaxation in response to ACh was significantly lower in smokers as compared with nonsmokers (n = 8 in each group), consistent with reduced eNOS activity in the former compared with the latter. eNOS protein expression remained, however, the same in both groups. Expression of ROCKs, guanosine triphosphate-RhoA and phosphorylated MYPT-1 were significantly increased in smokers compared with controls. Pulmonary endothelial dysfunction is present in smokers whose lung function has not yet been impaired. Reduced activity of eNOS accounts at least in part for this endothelial dysfunction. Increased expression and activity of ROCKs accounts for another part through direct or indirect inhibition of the Rho-A/ROCKs pathway on nitric oxide synthesis and sustained pulmonary vasoconstriction through inhibition of myosin phosphatase.

  5. Normal saline influences coagulation and endothelial function after traumatic brain injury and hemorrhagic shock in pigs

    DEFF Research Database (Denmark)

    Dekker, Simone E; Sillesen, Martin; Bambakidis, Ted

    2014-01-01

    BACKGROUND: Traumatic brain injury (TBI) and hemorrhagic shock (HS) are the leading causes of trauma-related deaths. These insults disrupt coagulation and endothelial systems. This study investigated whether previously reported differences in lesion size and brain swelling during normal saline (NS...... of endothelial activation (E-selectin, Intercellular adhesion molecule [ICAM]-1), coagulation activation (prothrombin fragment 1 + 2), and natural anticoagulation (activated protein C [aPC]) were determined in serum and brain whole cell lysates. RESULTS: Serum levels of aPC were greater in the NS group (203 ± 30...... pg/mL) compared with HEX (77 ± 28 pg/mL; P = .02) and FFP (110 ± 28 pg/mL; P = .09), as was PF 1 + 2 in the brain when compared with FFP (PF 1 + 2, 89 ± 46 vs 37 ± 14 ng/mL; P = .035). Brain E-selectin was greater in the NS group compared with FFP (3.36 ± 0.02 vs 3.31 ± 0.01 ng/mL; P = .029...

  6. Serum nitrate levels as an index of endothelial function in pre-eclamsia and normal pregnancy.

    Science.gov (United States)

    Gupta, Rani; Maruthy, K N; Mhaskar, Arun M; Padmanabhan, Laxmi Devi

    2003-04-01

    The study was conducted in St. John's Medical College Hospital and Department of Physiology, with the aim of studying the serum nitrate levels in pre-eclampsia and normal pregnancy. The total number of subjects studied in various groups were 159, control (n = 55), first trimester (n = 13), second trimester normal (n = 42), second trimester pre-eclampsia/PET (n = 5), third trimester normal (n = 32), third trimester pre-eclampsia/PET (n = 12). The serum nitrate was measured by one step enzymatic assay using Nitrate reductase from Aspergillus species. The nitrate levels in the third trimester pre-eclamptic group was found to be significant lower (P = 0.02), as compared to normal subjects, however the renal functions were normal in all the subjects.

  7. Diet and Endothelial Function

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    ADA M CUEVAS

    2004-01-01

    Full Text Available Endothelial dysfunction is one of the earliest events in atherogenesis. A consequence of endothelial damage is a lower availability of nitric oxide (NO, the most potent endogenous vasodilator. NO inhibits platelet aggregation, smooth muscle cell proliferation and adhesion of monocytes to endothelial cells. Endothelial dysfunction is present in patients with cardiovascular disease and/or coronary risk factors, such as hypertension, dyslipidemia, diabetes, smoking or hyperhomocysteinemia. At present, soluble markers and high resolution ultrasound of the brachial artery, have provided simple tools for the study of endothelial function and the effects of several interventions. It has been demonstrated that dietary factors may induce significant changes on vascular reactivity. Nutrients, such as fish oil, antioxidants, L-arginine, folic acid and soy protein have shown an improvement in endothelial function that can mediate, at least partially, the cardioprotective effects of these substances. Attention has been focused on dietary patterns in populations with lower prevalence of cardiovascular disease. There is some evidence suggesting that Mediterranean diet characterized by high consumption of vegetables, fish, olive oil and moderate wine consumption may have a positive effect on endothelial function. These results give us evidence on the significant role of diet on endothelial function and its impact on the pathogenesis of atherosclerosis

  8. Endothelial RIG-I activation impairs endothelial function

    International Nuclear Information System (INIS)

    Asdonk, Tobias; Motz, Inga; Werner, Nikos; Coch, Christoph; Barchet, Winfried; Hartmann, Gunther; Nickenig, Georg; Zimmer, Sebastian

    2012-01-01

    Highlights: ► RIG-I activation impairs endothelial function in vivo. ► RIG-I activation alters HCAEC biology in vitro. ► EPC function is affected by RIG-I stimulation in vitro. -- Abstract: Background: Endothelial dysfunction is a crucial part of the chronic inflammatory atherosclerotic process and is mediated by innate and acquired immune mechanisms. Recent studies suggest that pattern recognition receptors (PRR) specialized in immunorecognition of nucleic acids may play an important role in endothelial biology in a proatherogenic manner. Here, we analyzed the impact of endothelial retinoic acid inducible gene I (RIG-I) activation upon vascular endothelial biology. Methods and results: Wild type mice were injected intravenously with 32.5 μg of the RIG-ligand 3pRNA (RNA with triphosphate at the 5′end) or polyA control every other day for 7 days. In 3pRNA-treated mice, endothelium-depended vasodilation was significantly impaired, vascular oxidative stress significantly increased and circulating endothelial microparticle (EMP) numbers significantly elevated compared to controls. To gain further insight in RIG-I dependent endothelial biology, cultured human coronary endothelial cells (HCAEC) and endothelial progenitor cells (EPC) were stimulated in vitro with 3pRNA. Both cells types express RIG-I and react with receptor upregulation upon stimulation. Reactive oxygen species (ROS) formation is enhanced in both cell types, whereas apoptosis and proliferation is not significantly affected in HCAEC. Importantly, HCAEC release significant amounts of proinflammatory cytokines in response to RIG-I stimulation. Conclusion: This study shows that activation of the cytoplasmatic nucleic acid receptor RIG-I leads to endothelial dysfunction. RIG-I induced endothelial damage could therefore be an important pathway in atherogenesis.

  9. Endothelial RIG-I activation impairs endothelial function

    Energy Technology Data Exchange (ETDEWEB)

    Asdonk, Tobias, E-mail: tobias.asdonk@ukb.uni-bonn.de [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Motz, Inga; Werner, Nikos [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Coch, Christoph; Barchet, Winfried; Hartmann, Gunther [Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Nickenig, Georg; Zimmer, Sebastian [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany)

    2012-03-30

    Highlights: Black-Right-Pointing-Pointer RIG-I activation impairs endothelial function in vivo. Black-Right-Pointing-Pointer RIG-I activation alters HCAEC biology in vitro. Black-Right-Pointing-Pointer EPC function is affected by RIG-I stimulation in vitro. -- Abstract: Background: Endothelial dysfunction is a crucial part of the chronic inflammatory atherosclerotic process and is mediated by innate and acquired immune mechanisms. Recent studies suggest that pattern recognition receptors (PRR) specialized in immunorecognition of nucleic acids may play an important role in endothelial biology in a proatherogenic manner. Here, we analyzed the impact of endothelial retinoic acid inducible gene I (RIG-I) activation upon vascular endothelial biology. Methods and results: Wild type mice were injected intravenously with 32.5 {mu}g of the RIG-ligand 3pRNA (RNA with triphosphate at the 5 Prime end) or polyA control every other day for 7 days. In 3pRNA-treated mice, endothelium-depended vasodilation was significantly impaired, vascular oxidative stress significantly increased and circulating endothelial microparticle (EMP) numbers significantly elevated compared to controls. To gain further insight in RIG-I dependent endothelial biology, cultured human coronary endothelial cells (HCAEC) and endothelial progenitor cells (EPC) were stimulated in vitro with 3pRNA. Both cells types express RIG-I and react with receptor upregulation upon stimulation. Reactive oxygen species (ROS) formation is enhanced in both cell types, whereas apoptosis and proliferation is not significantly affected in HCAEC. Importantly, HCAEC release significant amounts of proinflammatory cytokines in response to RIG-I stimulation. Conclusion: This study shows that activation of the cytoplasmatic nucleic acid receptor RIG-I leads to endothelial dysfunction. RIG-I induced endothelial damage could therefore be an important pathway in atherogenesis.

  10. Initial contact of glioblastoma cells with existing normal brain endothelial cells strengthen the barrier function via fibroblast growth factor 2 secretion: a new in vitro blood-brain barrier model.

    Science.gov (United States)

    Toyoda, Keisuke; Tanaka, Kunihiko; Nakagawa, Shinsuke; Thuy, Dinh Ha Duy; Ujifuku, Kenta; Kamada, Kensaku; Hayashi, Kentaro; Matsuo, Takayuki; Nagata, Izumi; Niwa, Masami

    2013-05-01

    Glioblastoma multiforme (GBM) cells invade along the existing normal capillaries in brain. Normal capillary endothelial cells function as the blood-brain barrier (BBB) that limits permeability of chemicals into the brain. To investigate whether GBM cells modulate the BBB function of normal endothelial cells, we developed a new in vitro BBB model with primary cultures of rat brain endothelial cells (RBECs), pericytes, and astrocytes. Cells were plated on a membrane with 8 μm pores, either as a monolayer or as a BBB model with triple layer culture. The BBB model consisted of RBEC on the luminal side as a bottom, and pericytes and astrocytes on the abluminal side as a top of the chamber. Human GBM cell line, LN-18 cells, or lung cancer cell line, NCI-H1299 cells, placed on either the RBEC monolayer or the BBB model increased the transendothelial electrical resistance (TEER) values against the model, which peaked within 72 h after the tumor cell application. The TEER value gradually returned to baseline with LN-18 cells, whereas the value quickly dropped to the baseline in 24 h with NCI-H1299 cells. NCI-H1299 cells invaded into the RBEC layer through the membrane, but LN-18 cells did not. Fibroblast growth factor 2 (FGF-2) strengthens the endothelial cell BBB function by increased occludin and ZO-1 expression. In our model, LN-18 and NCI-H1299 cells secreted FGF-2, and a neutralization antibody to FGF-2 inhibited LN-18 cells enhanced BBB function. These results suggest that FGF-2 would be a novel therapeutic target for GBM in the perivascular invasive front.

  11. Normal Functioning Family

    Science.gov (United States)

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Español Text Size Email Print Share Normal Functioning Family Page Content Article Body Is there any way ...

  12. Circulating humanin levels are associated with preserved coronary endothelial function.

    Science.gov (United States)

    Widmer, R J; Flammer, A J; Herrmann, J; Rodriguez-Porcel, M; Wan, J; Cohen, P; Lerman, L O; Lerman, A

    2013-02-01

    Humanin is a small endogenous antiapoptotic peptide, originally identified as protective against Alzheimer's disease, but subsequently also found on human endothelium as well as carotid artery plaques. Endothelial dysfunction is a precursor to the development of atherosclerotic plaques, which are characterized by a highly proinflammatory, reactive oxygen species, and apoptotic milieu. Previous animal studies demonstrated that humanin administration may improve endothelial function. Thus the aim of this study was to test the hypothesis that patients with coronary endothelial dysfunction have reduced systemic levels of humanin. Forty patients undergoing coronary angiography and endothelial function testing were included and subsequently divided into two groups based on coronary blood flow (CBF) response to intracoronary acetylcholine (normal ≥ 50% increase from baseline, n = 20 each). Aortic plasma samples were obtained at the time of catheterization for the analysis of humanin levels and traditional biomarkers of atherosclerosis including C-reactive protein, Lp-Pla(2), and homocysteine. Baseline characteristics were similar in both groups. Patients with coronary endothelial dysfunction (change in CBF = -33 ± 25%) had significantly lower humanin levels (1.3 ± 1.1 vs. 2.2 ± 1.5 ng/ml, P = 0.03) compared with those with normal coronary endothelial function (change in CBF = 194 ± 157%). There was a significant and positive correlation between improved CBF and humanin levels (P = 0.0091) not seen with changes in coronary flow reserve (P = 0.76). C-reactive protein, Lp-Pla(2), and homocysteine were not associated with humanin levels. Thus we observed that preserved human coronary endothelial function is uniquely associated with higher systemic humanin levels, introducing a potential diagnostic and/or therapeutic target for patients with coronary endothelial function.

  13. Mitochondria, endothelial cell function, and vascular diseases.

    Science.gov (United States)

    Tang, Xiaoqiang; Luo, Yu-Xuan; Chen, Hou-Zao; Liu, De-Pei

    2014-01-01

    Mitochondria are perhaps the most sophisticated and dynamic responsive sensing systems in eukaryotic cells. The role of mitochondria goes beyond their capacity to create molecular fuel and includes the generation of reactive oxygen species, the regulation of calcium, and the activation of cell death. In endothelial cells, mitochondria have a profound impact on cellular function under both healthy and diseased conditions. In this review, we summarize the basic functions of mitochondria in endothelial cells and discuss the roles of mitochondria in endothelial dysfunction and vascular diseases, including atherosclerosis, diabetic vascular dysfunction, pulmonary artery hypertension, and hypertension. Finally, the potential therapeutic strategies to improve mitochondrial function in endothelial cells and vascular diseases are also discussed, with a focus on mitochondrial-targeted antioxidants and calorie restriction.

  14. Mitochondria, Endothelial Cell Function and Vascular Diseases

    Directory of Open Access Journals (Sweden)

    Xiaoqiang eTang

    2014-05-01

    Full Text Available Mitochondria are perhaps the most sophisticated and dynamic responsive sensing systems in eukaryotic cells. The role of mitochondria goes beyond their capacity to create molecular fuel and includes the generation of reactive oxygen species, the regulation of calcium, and the activation of cell death. In endothelial cells, mitochondria have a profound impact on cellular function under both healthy and diseased conditions. In this review, we summarize the basic functions of mitochondria in endothelial cells and discuss the roles of mitochondria in endothelial dysfunction and vascular diseases, including atherosclerosis, diabetic vascular dysfunction, pulmonary artery hypertension and hypertension. Finally, the potential therapeutic strategies to improve mitochondrial function in endothelial cells and vascular diseases are also discussed, with a focus on mitochondrial-targeted antioxidants and calorie restriction.

  15. [Assessment of endothelial function in autoimmune diseases].

    Science.gov (United States)

    Benhamou, Y; Bellien, J; Armengol, G; Gomez, E; Richard, V; Lévesque, H; Joannidès, R

    2014-08-01

    Numerous autoimmune-inflammatory rheumatic diseases have been associated with accelerated atherosclerosis or other types of vasculopathy leading to an increase in cardiovascular disease incidence. In addition to traditional cardiovascular risk factors, endothelial dysfunction is an important early event in the pathogenesis of atherosclerosis, contributing to plaque initiation and progression. Endothelial dysfunction is characterized by a shift of the actions of the endothelium toward reduced vasodilation, a proinflammatory and a proadhesive state, and prothrombic properties. Therefore, assessment of endothelial dysfunction targets this vascular phenotype using several biological markers as indicators of endothelial dysfunction. Measurements of soluble adhesion molecules (ICAM-1, VCAM-1, E-selectin), pro-thrombotic factors (thrombomodulin, von Willebrand factor, plasminogen activator inhibitor-1) and inflammatory cytokines are most often performed. Regarding the functional assessment of the endothelium, the flow-mediated dilatation of conduit arteries is a non-invasive method widely used in pathophysiological and interventional studies. In this review, we will briefly review the most relevant information upon endothelial dysfunction mechanisms and explorations. We will summarize the similarities and differences in the biological and functional assessments of the endothelium in different autoimmune diseases. Copyright © 2013 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  16. 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.

  17. Endothelial function in postmenopausal women with nighttime systolic hypertension.

    Science.gov (United States)

    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.

  18. Arterial endothelial function measurement method and apparatus

    Science.gov (United States)

    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.

  19. Endothelial Function in a Mouse Model of Myeloperoxidase Deficiency

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    Veronika Golubinskaya

    2014-01-01

    Full Text Available Myeloperoxidase (MPO activity is suggested to reduce the function of vascular nitric oxide, thereby contributing to endothelial dysfunction, although data in rodents are inconclusive. We examined vascular contractile and relaxant responses in MPO-deficient (MPO-/- and wild-type mice to investigate the role for myeloperoxidase in the development of endothelial dysfunction. Carotid and saphenous arteries were taken from 8-month-old mice and studied in a myograph. Responses of carotid arteries to phenylephrine, high potassium, or acetylcholine (Ach were statistically not different from controls. Treatment with lipopolysaccharide (LPS; to enhance endothelial dysfunction reduced responses to Ach in MPO-/- but did not affect responses in wild-type. In response to high concentrations of Ach, carotid arteries responded with transient contractions, which were not different between the groups and not affected by LPS treatment. Saphenous arteries from MPO-/- had smaller normalized diameters and developed less contractile force. Vessels from MPO-/- were less sensitive to Ach than controls. These data suggest that mature MPO-deficient mice do not show enhanced endothelial function compared to wild-type mice, even when provoked with LPS treatment. The EDHF response appears to be reduced in MPO deficiency.

  20. Homocyst(e)ine impairs endocardial endothelial function.

    Science.gov (United States)

    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.

  1. Endothelial cells stimulate growth of normal and cancerous breast epithelial cells in 3D culture

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    Magnusson Magnus K

    2010-07-01

    Full Text Available Abstract Background Epithelial-stromal interaction provides regulatory signals that maintain correct histoarchitecture and homeostasis in the normal breast and facilitates tumor progression in breast cancer. However, research on the regulatory role of the endothelial component in the normal and malignant breast gland has largely been neglected. The aim of the study was to investigate the effects of endothelial cells on growth and differentiation of human breast epithelial cells in a three-dimensional (3D co-culture assay. Methods Breast luminal and myoepithelial cells and endothelial cells were isolated from reduction mammoplasties. Primary cells and established normal and malignant breast cell lines were embedded in reconstituted basement membrane in direct co-culture with endothelial cells and by separation of Transwell filters. Morphogenic and phenotypic profiles of co-cultures was evaluated by phase contrast microscopy, immunostaining and confocal microscopy. Results In co-culture, endothelial cells stimulate proliferation of both luminal- and myoepithelial cells. Furthermore, endothelial cells induce a subpopulation of luminal epithelial cells to form large acini/ducts with a large and clear lumen. Endothelial cells also stimulate growth and cloning efficiency of normal and malignant breast epithelial cell lines. Transwell and gradient co-culture studies show that endothelial derived effects are mediated - at least partially - by soluble factors. Conclusion Breast endothelial cells - beside their role in transporting nutrients and oxygen to tissues - are vital component of the epithelial microenvironment in the breast and provide proliferative signals to the normal and malignant breast epithelium. These growth promoting effects of endothelial cells should be taken into consideration in breast cancer biology.

  2. Circulating vascular endothelial growth factor during the normal menstrual cycle

    NARCIS (Netherlands)

    Kusumanto, YH; Hospers, GAP; Sluiter, WJ; Dam, WA; Meijer, C; Mulder, NH

    2004-01-01

    Background: The purpose of the study was to investigate whether cycle-related variations in circulating Vascular Endothelial Growth Factor (VEGF) levels would increase the metastatic potential at specific times during the menstrual cycle. Materials and Methods: VEGF levels in serum and whole blood

  3. Endothelial Function in Migraine With Aura – A Systematic Review

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND: An increased risk of ischemic stroke is repeatedly reported in young subjects with migraine with aura (MA). Such may be caused by changes in endothelial function. The present review evaluates current evidence on endothelial function in MA patients. METHODS: A systematic search...... in patients indicating a possible subtle change in the endothelium. Further investigations on larger groups of patients combining testing of endothelial dysfunction as well as biomarkers are warranted to identify whether or not endothelial changes may play a role in the increased risk of stroke in young MA...

  4. 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 ...

  5. 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

  6. Cytoskeleton, cytoskeletal interactions, and vascular endothelial function

    Directory of Open Access Journals (Sweden)

    Wang J

    2012-12-01

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

  7. Curcumin and Endothelial Function: Evidence and Mechanisms of Protective Effects.

    Science.gov (United States)

    Karimian, Maryam S; Pirro, Matteo; Johnston, Thomas P; Majeed, Muhammed; Sahebkar, Amirhossein

    2017-01-01

    The endothelium is a large paracrine organ regulating cell growth, vascular tone and thrombogenicity as well as platelet and leukocyte interactions. Endothelial function can be assessed by noninvasive techniques [e.g. flow-mediated vasodilation, nitroglycerin-mediated dilation and pulse wave velocity] and measuring specific circulating biomarkers [cell adhesion molecules, endothelial microparticles and endothelial progenitor cells]. Impaired endothelial function plays a key role in the development of atherosclerosis, arterial hypertension, heart failure, ischemia-reperfusion injury, Alzheimer's disease and other conditions. Endothelial function is also involved in growth and proliferation of tumor cells. We performed a literature review and assessed the role of the natural polyphenol, curcumin, as a potential inexpensive, well-tolerated, and safe agent for improving endothelial function. Curcumin exerts several positive pharmacological effects; these include anti-inflammatory, antioxidant, anti-hypertensive, anti-cancer, antiviral, anti-infective and wound-healing properties. Specifically, curcumin's anti-inflammatory effects are thought to be caused by reducing trans-endothelial monocyte migration by reduction of mRNA and protein expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and P-selectin and by modulating NFκB, JNK, p38 and STAT-3 in endothelial cells. Dietary curcumin supplementation can also increase antioxidant activity through the induction of heme oxygenase-1, a scavenger of free radicals, and by reduction of reactive oxygen species and Nox-2. Curcumin appears to improve endothelial function but additional research is needed to determine the precise mechanism(s) and biomarkers involved in curcumin's therapeutic effects on endothelial dysfunction. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. 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...

  9. Regulation of brain endothelial barrier function by microRNAs in health and neuroinflammation.

    Science.gov (United States)

    Lopez-Ramirez, Miguel Alejandro; Reijerkerk, Arie; de Vries, Helga E; Romero, Ignacio Andres

    2016-08-01

    Brain endothelial cells constitute the major cellular element of the highly specialized blood-brain barrier (BBB) and thereby contribute to CNS homeostasis by restricting entry of circulating leukocytes and blood-borne molecules into the CNS. Therefore, compromised function of brain endothelial cells has serious consequences for BBB integrity. This has been associated with early events in the pathogenesis of several disorders that affect the CNS, such as multiple sclerosis, HIV-associated neurologic disorder, and stroke. Recent studies demonstrate that brain endothelial microRNAs play critical roles in the regulation of BBB function under normal and neuroinflammatory conditions. This review will focus on emerging evidence that indicates that brain endothelial microRNAs regulate barrier function and orchestrate various phases of the neuroinflammatory response, including endothelial activation in response to cytokines as well as restoration of inflamed endothelium into a quiescent state. In particular, we discuss novel microRNA regulatory mechanisms and their contribution to cellular interactions at the neurovascular unit that influence the overall function of the BBB in health and during neuroinflammation.-Lopez-Ramirez, M. A., Reijerkerk, A., de Vries, H. E., Romero, I. A. Regulation of brain endothelial barrier function by microRNAs in health and neuroinflammation. © The Author(s).

  10. Postprandial lipaemia, oxidative stress and endothelial function: a review.

    Science.gov (United States)

    Wallace, J P; Johnson, B; Padilla, J; Mather, K

    2010-02-01

    Postprandial lipaemia-induced endothelial dysfunction is felt to be mediated by increases in oxidative stress. In this review, we have examined the cross-sectional relationships found among these three variables. We found 20 studies conducted by 16 independent investigative teams through a Medline search from 1980 to 2008; studies were required to report correlations between at least two of the three variables of interest in studies of humans. This review is divided into (i) discussions on the biomarkers and other measures of postprandial lipaemia, oxidative stress and endothelial function; (ii) associations reported among the three variables; and (iii) other considerations including alternative intervention studies. Triglycerides and free fatty acids are robust and well-standardised biomarkers of lipaemia. Measures of oxidative stress ranged from electron spin techniques to measures of lipid peroxidation and are limited by lack of standardisation. Brachial artery flow-mediated dilatation is the most commonly used measure of endothelial function. The associations between postprandial lipaemia and oxidative stress and between postprandial lipaemia and endothelial function are strong and consistent. However, the association between postprandial oxidative stress and endothelial function appears weak, at least using current approaches to measurement of oxidative stress. These observations are consistent with the proposed concept that oxidative stress mediates the adverse effects of postprandial lipaemia on endothelial function; they are limited by the difficulties in measuring oxidative stress. Efforts directed at optimising and standardising the measurement of oxidative stress will be of value in future works in this area.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. 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.

  13. 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

  14. Folic acid supplementation normalizes the endothelial progenitor cell transcriptome of patients with type 1 diabetes: a case-control pilot study

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    Stubbs Andrew

    2009-08-01

    Full Text Available Abstract Background Endothelial progenitor cells play an important role in vascular wall repair. Patients with type 1 diabetes have reduced levels of endothelial progenitor cells of which their functional capacity is impaired. Reduced nitric oxide bioavailability and increased oxidative stress play a role in endothelial progenitor cell dysfunction in these patients. Folic acid, a B-vitamin with anti-oxidant properties, may be able to improve endothelial progenitor cell function. In this study, we investigated the gene expression profiles of endothelial progenitor cells from patients with type 1 diabetes compared to endothelial progenitor cells from healthy subjects. Furthermore, we studied the effect of folic acid on gene expression profiles of endothelial progenitor cells from patients with type 1 diabetes. Methods We used microarray analysis to investigate the gene expression profiles of endothelial progenitor cells from type 1 diabetes patients before (n = 11 and after a four week period of folic acid supplementation (n = 10 compared to the gene expression profiles of endothelial progenitor cells from healthy subjects (n = 11. The probability of genes being differentially expressed among the classes was computed using a random-variance t-test. A multivariate permutation test was used to identify genes that were differentially expressed among the two classes. Functional classification of differentially expressed genes was performed using the biological process ontology in the Gene Ontology database. Results Type 1 diabetes significantly modulated the expression of 1591 genes compared to healthy controls. These genes were found to be involved in processes regulating development, cell communication, cell adhesion and localization. After folic acid treatment, endothelial progenitor cell gene expression profiles from diabetic patients were similar to those from healthy controls. Genes that were normalized by folic acid played a prominent role in

  15. Torcetrapib impairs endothelial function in hypertension.

    Science.gov (United States)

    Simic, Branko; Hermann, Matthias; Shaw, Sidney G; Bigler, Laurent; Stalder, Urs; Dörries, Carola; Besler, Christian; Lüscher, Thomas F; Ruschitzka, Frank

    2012-07-01

    A marked increase in HDL notwithstanding, the cholesterol ester transfer protein (CETP) inhibitor torcetrapib was associated with an increase in all-cause mortality in the ILLUMINATE trial. As underlying mechanisms remain elusive, the present study was designed to delineate potential off-target effects of torcetrapib. Spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats were treated with torcetrapib (100 mg/kg/day; SHR-T and WKY-T) or placebo (SHR-P and WKY-P) for 3 weeks. Blood pressure transiently increased during the first 3 days of torcetrapib administration in SHRs and returned to baseline thereafter despite continued drug administration. Acetylcholine-induced endothelium-dependent relaxations of aortic rings were markedly impaired, and endothelial nitric oxide synthase (eNOS) mRNA and protein were down-regulated after 3 weeks of torcetrapib treatment in SHR (P risk is exposed to these compounds.

  16. 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

  17. Caveolae, caveolins, cavins and endothelial cell function: new insights

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    Grzegorz eSowa

    2012-01-01

    Full Text Available Caveolae are cholesterol and glycosphingolipid-rich flask-shaped invaginations of the plasma membrane which are particularly abundant in vascular endothelium and present in all other cell types of the cardiovascular system, including vascular smooth muscle cells, macrophages, cardiac myocytes, and fibroblasts. Caveolins and the more recently discovered cavins are the major protein components of caveolae. When caveolae were discovered, their functional role was believed to be limited to transport across the endothelial cell barrier. Since then, however, a large body of evidence has accumulated, suggesting that these microdomains are very important in regulating many other important endothelial cell functions, mostly due to their ability to concentrate and compartmentalize various signaling molecules. Over the course of several years, multiple studies involving knockout mouse and small interfering RNA approaches have considerably enhanced our understanding of the role of caveolae and caveolin-1 in regulating many cardiovascular functions. New findings have been reported implicating other caveolar protein components in endothelial cell signaling and function, such as the understudied caveolin-2 and newly discovered cavin proteins. The aim of this review is to focus primarily on molecular and cellular aspects of the role of caveolae, caveolins, and cavins in endothelial cell signaling and function. In addition, where appropriate, the possible implications for the cardiovascular and pulmonary physiology and pathophysiology will be discussed.

  18. Influence of abdominal obesity on vascular endothelial function in overweight/obese adult men.

    Science.gov (United States)

    Weil, Brian R; Stauffer, Brian L; Mestek, Michael L; DeSouza, Christopher A

    2011-09-01

    It has been suggested that body fat distribution may be an important determinant of the impact of adiposity on endothelial function. We tested the hypothesis that overweight/obese adults with abdominal adiposity exhibit worse endothelial vasodilator and fibrinolytic function than overweight/obese adults without abdominal adiposity. Sixty adult men were studied: 20 normal weight (BMI: 22.3 ± 0.7 kg/m2; waist circumference (WC): 84.9 ± 2.0 cm); 20 overweight/obese with WC obese with WC ≥102 cm (30.0 ± 0.4 kg/m2; 106.7 ± 1.0 cm). Forearm blood flow (FBF) responses to intra-arterial acetylcholine and sodium nitroprusside (SNP) were measured. Additionally, net endothelial release of tissue-type plasminogen activator (t-PA) was determined in response to bradykinin (BK) and SNP. Overweight/obese men demonstrated lower (~30%; P obese men with (4.1 ± 0.3-10.8 ± 1.3 ml/100 ml tissue/min) and without (4.5 ± 0.3-11.6 ± 0.8 ml/100 ml tissue/min) abdominal adiposity. Similarly, endothelial t-PA release to BK was lower (~40%; P obese men compared with normal weight controls; however, t-PA release was not different between the overweight/obese men with (-0.7 ± 0.4-40.4 ± 6.2 ng/100 ml tissue/min) and without (-0.3 ± 0.6-48 ± 7.5 ng/100 ml tissue/min) abdominal adiposity. These results indicate that abdominal obesity is not associated with greater impairment in endothelial vasodilation and fibrinolytic capacity in overweight/obese men. Excess adiposity, regardless of anatomical distribution pattern, is associated with impaired endothelial function.

  19. Weight loss improves biomarkers endothelial function and systemic ...

    African Journals Online (AJOL)

    Weight loss improves biomarkers endothelial function and systemic inflammation in obese postmenopausal Saudi women. Shehab Mahmoud Abd El- Kader1, Mohammed H Saiem Al-Dahr2. 1. Department of Physical Therapy, Faculty of Applied Medical Sciences, King Abdulaziz University. 2. Department of Medical ...

  20. 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

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

    Science.gov (United States)

    Sverrisdóttir, Yrsa Bergmann; Jansson, Linda Marie; Hägg, Ulrika; Gan, Li-Ming

    2010-02-17

    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. 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). 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 health.

  2. Endothelial Function in Distinct Phenotypes of Obesity

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    Şule Temizkan

    2016-12-01

    Full Text Available Purpose: In our study, we aimed to determine whether metabolically healthy subjects with obesity would show endothelial dysfunction (ED when compared with insulin-resistant subjects with obesity. Material and Method: We enrolled 231 subjects with obesity (83% female in this cross-sectional study. Brachial artery flow-mediated dilation was performed by Doppler ultrasonography and a standard 75-g oral glucose tolerance test were carried out in all participants. The subjects were stratified into tertiles based on their insulin sensitivity index values and defined as having insulin-resistant obesity if the values were in the lower tertile (n=77 or metabolically healthy obesity if the values were in the upper tertile (n=77. ED was defined as Δ flow-mediated dilation <4.5%. Results: Metabolically healthy obesity and insulin-resistant obesity groups had similar ages (39±9 vs. 40±10 years; p=0.59 and body mass index (38±5 vs. 39±5 kg/m2; p=0.09. Waist circumference (101±11 vs. 106±13 cm; p=0.01, fasting blood glucose (87±9 vs. 97±13 mg/dL; p<0.001, diastolic blood pressure (79±11 vs. 82±12 mmHg; p=0.04 and uric acid levels (4.6±1.0 vs. 5.3±1.3 mg/dL; p<0.001 were lower in metabolically healthy obesity subjects, however, the incidence of ED was similar in both metabolically healthy obesity and insulin-resistant obesity subjects (80% vs. 71%; p=0.25, respectively. Discussion: The incidence of ED, assessed by flow-mediated dilation, was similar both in metabolically healthy obesity and insulin-resistant obesity subjects. In this study, we showed that subjects with obesity as defined as metabolically healthy obesity might also show ED.

  3. Atorvastatin affects negatively respiratory function of isolated endothelial mitochondria.

    Science.gov (United States)

    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.

  4. 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

  5. Deleterious effects of phosphate on vascular and endothelial function via disruption to the nitric oxide pathway.

    Science.gov (United States)

    Stevens, Kathryn K; Denby, Laura; Patel, Rajan K; Mark, Patrick B; Kettlewell, Sarah; Smith, Godfrey L; Clancy, Marc J; Delles, Christian; Jardine, Alan G

    2017-10-01

    Hyperphosphataemia is an independent risk factor for accelerated cardiovascular disease in chronic kidney disease (CKD), although the mechanism for this is poorly understood. We investigated the effects of sustained exposure to a high-phosphate environment on endothelial function in cellular and preclinical models, as well as in human subjects. Resistance vessels from rats and humans (± CKD) were incubated in a normal (1.18 mM) or high (2.5 mM) phosphate concentration solution and cells were cultured in normal- (0.5 mM) or high-phosphate (3 mM) concentration media. A single-blind crossover study was performed in healthy volunteers, receiving phosphate supplements or a phosphate binder (lanthanum), and endothelial function measured was by flow-mediated dilatation. Endothelium-dependent vasodilatation was impaired when resistance vessels were exposed to high phosphate; this could be reversed in the presence of a phosphodiesterase-5-inhibitor. Vessels from patients with CKD relaxed normally when incubated in normal-phosphate conditions, suggesting that the detrimental effects of phosphate may be reversible. Exposure to high-phosphate disrupted the whole nitric oxide pathway with reduced nitric oxide and cyclic guanosine monophosphate production and total and phospho endothelial nitric oxide synthase expression. In humans, endothelial function was reduced by chronic phosphate loading independent of serum phosphate, but was associated with higher urinary phosphate excretion and serum fibroblast growth factor 23. These directly detrimental effects of phosphate, independent of other factors in the uraemic environment, may explain the increased cardiovascular risk associated with phosphate in CKD.

  6. XIAP reverses various functional activities of FRNK in endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Sunyoung; Kim, Hyun Jeong [Department of Molecular Biology and Institute of Nanosensor and Biotechnology, BK21 Graduate Program for RNA Biology, Dankook Univiersity, 126, Jukjeon-dong, Suji-gu, Yongin-si, Gyeonggi-do 448-701 (Korea, Republic of); Chi, Sung-Gil [School of Life Sciences and Biotechnology, Korea University, Seoul 136-701 (Korea, Republic of); Park, Heonyong, E-mail: heonyong@dankook.ac.kr [Department of Molecular Biology and Institute of Nanosensor and Biotechnology, BK21 Graduate Program for RNA Biology, Dankook Univiersity, 126, Jukjeon-dong, Suji-gu, Yongin-si, Gyeonggi-do 448-701 (Korea, Republic of)

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer FRNK domain is recruited into focal adhesion (FA), controlling endothelial cell adhesion. Black-Right-Pointing-Pointer XIAP binds the FRNK domain of FAK. Black-Right-Pointing-Pointer XIAP inhibits recruitment of FRNK into Fas and FRNK-promoted cell adhesion. Black-Right-Pointing-Pointer 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.

  7. 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 ch...... in hypercholesterolemic patients. Also, the increased level of plasma endothelial markers found in HIV patients was not related to hypercholesterolemia....

  8. Endothelial cell senescence with aging in healthy humans: prevention by habitual exercise and relation to vascular endothelial function.

    Science.gov (United States)

    Rossman, Matthew J; Kaplon, Rachelle E; Hill, Sierra D; McNamara, Molly N; Santos-Parker, Jessica R; Pierce, Gary L; Seals, Douglas R; Donato, Anthony J

    2017-11-01

    Cellular senescence is emerging as a key mechanism of age-related vascular endothelial dysfunction, but evidence in healthy humans is lacking. Moreover, the influence of lifestyle factors such as habitual exercise on endothelial cell (EC) senescence is unknown. We tested the hypothesis that EC senescence increases with sedentary, but not physically active, aging and is associated with vascular endothelial dysfunction. Protein expression (quantitative immunofluorescence) of p53, a transcription factor related to increased cellular senescence, and the cyclin-dependent kinase inhibitors p21 and p16 were 116%, 119%, and 128% greater (all P 0.05) in venous ECs from older exercising adults (57 ± 1 yr, n = 13). Furthermore, venous EC protein levels of p53 ( r  = -0.49, P = 0.003), p21 ( r  = -0.38, P = 0.03), and p16 ( r  = -0.58, P = 0.002) were inversely associated with vascular endothelial function (brachial artery flow-mediated dilation). Similarly, protein expression of p53 and p21 was 26% and 23% higher (both P 0.05) in older habitually exercising adults (59 ± 1 yr, n = 14). These data indicate that EC senescence is associated with sedentary aging and is linked to endothelial dysfunction. Moreover, these data suggest that prevention of EC senescence may be one mechanism by which aerobic exercise protects against endothelial dysfunction with age. NEW & NOTEWORTHY Our study provides novel evidence in humans of increased endothelial cell senescence with sedentary aging, which is associated with impaired vascular endothelial function. Furthermore, our data suggest an absence of age-related increases in endothelial cell senescence in older exercising adults, which is linked with preserved vascular endothelial function. Copyright © 2017 the American Physiological Society.

  9. Olive oil polyphenols decrease blood pressure and improve endothelial function in young women with mild hypertension.

    Science.gov (United States)

    Moreno-Luna, Rafael; Muñoz-Hernandez, Rocio; Miranda, Maria L; Costa, Alzenira F; Jimenez-Jimenez, Luis; Vallejo-Vaz, Antonio J; Muriana, Francisco J G; Villar, Jose; Stiefel, Pablo

    2012-12-01

    Olive oil polyphenols have been associated with several cardiovascular health benefits. This study aims to examine the influence of a polyphenol-rich olive oil on blood pressure (BP) and endothelial function in 24 young women with high-normal BP or stage 1 essential hypertension. We conducted a double-blind, randomized, crossover dietary-intervention study. After a run-in period of 4 months (baseline values), two diets were used, one with polyphenol-rich olive oil (∼30 mg/day), the other with polyphenol-free olive oil. Each dietary period lasted 2 months with a 4-week washout between diets. Systolic and diastolic BP, serum or plasma biomarkers of endothelial function, oxidative stress, and inflammation, and ischemia-induced hyperemia in the forearm were measured. When compared to baseline values, only the polyphenol-rich olive oil diet led to a significant (P olive oil diet also elicited an increase in plasma nitrites/nitrates (+4.7 ± 6.6 µmol/l, P olive oil can decrease BP and improve endothelial function in young women with high-normal BP or stage 1 essential hypertension.

  10. Ingestion of broccoli sprouts does not improve endothelial function in humans with hypertension

    DEFF Research Database (Denmark)

    Christiansen, Buris; Bellostas Muguerza, Natalia; Petersen, Atheline Major

    2010-01-01

    UNLABELLED: Ingestion of glucosinolates has previously been reported to improve endothelial function in spontaneously hypertensive rats, possibly because of an increase in NO availability in the endothelium due to an attenuation of oxidative stress; in our study we tried to see if this also would...... be the case in humans suffering from essential hypertension. METHODS: 40 hypertensive individuals without diabetes and with normal levels of cholesterol were examined. The participants were randomized either to ingest 10 g dried broccoli sprouts, a natural donor of glucosinolates with high in vitro...... antioxidative potential, for a 4 week period or to continue their ordinary diet and act as controls. Blood pressure, endothelial function measured by flow mediated dilation (FMD) and blood samples were obtained from the participants every other week and the content of glucosinolates was measured before...

  11. Heavy Alcohol Consumption is Associated with Impaired Endothelial Function.

    Science.gov (United States)

    Tanaka, Aoi; Cui, Renzhe; Kitamura, Akihiko; Liu, Keyang; Imano, Hironori; Yamagishi, Kazumasa; Kiyama, Masahiko; Okada, Takeo; Iso, Hiroyasu

    2016-09-01

    Previous studies have reported that moderate alcohol consumption is protective against cardiovascular disease, but heavy alcohol consumption increases its risk. Endothelial dysfunction is hypothesized to contribute to the development of atherosclerosis and cardiovascular disease. However, few population-based studies have examined a potential effect of alcohol consumption on endothelial function. This study included 404 men aged 30-79 years who were recruited from residents in 2 communities under the Circulatory Risk in Communities Study in 2013 and 2014. We asked the individuals about the frequency and volume of alcohol beverages and converted the data into grams of ethanol per day. Endothelial function was assessed by brachial artery flow-mediated dilation (FMD) measurements during reactive hyperemia. We performed cross-sectional analysis of alcohol consumption and %FMD by logistic regression analysis, adjusting for age, baseline brachial artery diameter, body mass index, systolic blood pressure, low-density lipoprotein cholesterol, HbA1c, smoking, antihypertensive medication use, and community. Individuals who drank ≥ 46 g/day ethanol had a lower age-adjusted mean %FMD than non-drinkers (p<0.01). Compared with non-drinkers, the age-adjusted odds ratios (ORs) (95% confidence interval) of low %FMD (<5.3%) for former, light (<23.0 g/day ethanol), moderate (23.0-45.9 g/day ethanol), and heavy (≥ 46.0 g/day ethanol) drinkers were 1.61 (0.67-3.89), 0.84 (0.43-1.66), 1.09 (0.52-2.25), and 2.99 (1.56-5.70), respectively. The corresponding multivariable-adjusted ORs were 1.76 (0.69-4.50), 0.86 (0.42-1.76), 0.98 (0.45-2.12), and 2.39 (1.15-4.95), respectively. Heavy alcohol consumption may be an independent risk factor of endothelial dysfunction in Japanese men.

  12. Functional Definition of Progenitors Versus Mature Endothelial Cells Reveals Key SoxF-Dependent Differentiation Process.

    Science.gov (United States)

    Patel, Jatin; Seppanen, Elke J; Rodero, Mathieu P; Wong, Ho Yi; Donovan, Prudence; Neufeld, Zoltan; Fisk, Nicholas M; Francois, Mathias; Khosrotehrani, Kiarash

    2017-02-21

    During adult life, blood vessel formation is thought to occur via angiogenic processes involving branching from existing vessels. An alternate proposal suggests that neovessels form from endothelial progenitors able to assemble the intimal layers. We here aimed to define vessel-resident endothelial progenitors in vivo in a variety of tissues in physiological and pathological situations such as normal aorta, lungs, and wound healing, tumors, and placenta, as well. Based on protein expression levels of common endothelial markers using flow cytometry, 3 subpopulations of endothelial cells could be identified among VE-Cadherin+ and CD45- cells. Lineage tracing by using Cdh5cre ERt2 /Rosa-YFP reporter strategy demonstrated that the CD31-/loVEGFR2lo/intracellular endothelial population was indeed an endovascular progenitor (EVP) of an intermediate CD31intVEGFR2lo/intracellular transit amplifying (TA) and a definitive differentiated (D) CD31hiVEGFR2hi/extracellular population. EVP cells arose from vascular-resident beds that could not be transferred by bone marrow transplantation. Furthermore, EVP displayed progenitor-like status with a high proportion of cells in a quiescent cell cycle phase as assessed in wounds, tumors, and aorta. Only EVP cells and not TA and D cells had self-renewal capacity as demonstrated by colony-forming capacity in limiting dilution and by transplantation in Matrigel plugs in recipient mice. RNA sequencing revealed prominent gene expression differences between EVP and D cells. In particular, EVP cells highly expressed genes related to progenitor function including Sox9 , Il33 , Egfr , and Pdfgrα. Conversely, D cells highly expressed genes related to differentiated endothelium including Ets1&2 , Gata2 , Cd31 , Vwf , and Notch . The RNA sequencing also pointed to an essential role of the Sox18 transcription factor. The role of SOX18 in the differentiation process was validated by using lineage-tracing experiments based on S ox18Cre ERt2 /Rosa

  13. 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.

  14. Regulation and function of endothelial glycocalyx layer in vascular diseases.

    Science.gov (United States)

    Sieve, Irina; Münster-Kühnel, Anja K; Hilfiker-Kleiner, Denise

    2018-01-01

    In the vascular system, the endothelial surface layer (ESL) as the inner surface of blood vessels affects mechanotransduction, vascular permeability, rheology, thrombogenesis, and leukocyte adhesion. It creates barriers between endothelial cells and blood and neighbouring cells. The glycocalyx, composed of glycoconjugates and proteoglycans, is an integral component of the ESL and a key element in inter- and intracellular communication and tissue homeostasis. In pathophysiological conditions (atherosclerosis, infection, ischemia/reperfusion injury, diabetes, trauma and acute lung injury) glycocalyx-degrading factors, i.e. reactive oxygen and nitrogen species, matrix metalloproteinases, heparanase and sialidases, damage the ESL, thereby impairing endothelial functions. This leads to increased capillary permeability, leucocyte-endothelium interactions, thrombosis and vascular inflammation, the latter further driving glycocalyx destruction. The present review highlights current knowledge on the vasculoprotective role of the ESL, with specific emphasis on its remodelling in inflammatory vascular diseases and discusses its potential as a novel therapeutic target to treat vascular pathologies. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Borel functional calculus for quaternionic normal operators

    Science.gov (United States)

    Ramesh, G.; Santhosh Kumar, P.

    2017-05-01

    In this article, we give an approach to Borel functional calculus for quaternionic normal operators, which are not necessarily bounded. First, we establish the definition of functional calculus for a subclass of quaternion valued Borel functions, and then we extend the same to the class of quaternion valued Borel functions as well as L∞-functions. We also prove spectral mapping theorem as a consequence.

  16. Brief secondhand smoke exposure depresses endothelial progenitor cells activity and endothelial function: sustained vascular injury and blunted nitric oxide production.

    Science.gov (United States)

    Heiss, Christian; Amabile, Nicolas; Lee, Andrew C; Real, Wendy May; Schick, Suzaynn F; Lao, David; Wong, Maelene L; Jahn, Sarah; Angeli, Franca S; Minasi, Petros; Springer, Matthew L; Hammond, S Katharine; Glantz, Stanton A; Grossman, William; Balmes, John R; Yeghiazarians, Yerem

    2008-05-06

    This study sought to analyze the effects of acute secondhand smoke (SHS) exposure on the number and function of endothelial progenitor cells (EPCs) over 24 h. Secondhand smoke increases the risk of vascular disease and is a major public health concern, but the mechanism(s) of action are not fully understood. Healthy nonsmokers (age SEM 30.3 +/- 1.3 years, n = 10) were exposed to 30 min of SHS yielding cotinine levels commonly observed in passive smokers and to smokefree air on 2 separate days. Measurements were taken before exposure (baseline), immediately after (0 h), and at 1 h, 2.5 h, and 24 h after. The EPCs (CD133(+)/KDR(+), CD34(+)/KDR(+)) and endothelial microparticles (EMPs: CD31(+)/CD41(-), CD144(+), CD62e(+)) were determined in blood using flow cytometry. The EPC chemotaxis toward vascular endothelial growth factor was measured. Endothelial function was assessed as flow-mediated dilation (FMD) using ultrasound. Secondhand smoke exposure increased EPCs and plasma vascular endothelial growth factor and completely abolished EPC chemotaxis during 24 h after exposure. Secondhand smoke increased EMPs and decreased FMD. Although FMD returned to baseline at 2.5 h, EMPs and vascular endothelial growth factor levels remained elevated at 24 h, suggesting endothelial activation and injury with functional impairment of the vascular endothelium. Exposure to smokefree air had no effect. Incubation of EPCs from nonexposed subjects with plasma isolated from SHS-exposed subjects in vitro decreased chemotaxis by blockade of vascular endothelial growth factor-stimulated nitric oxide production. Brief exposure to real-world levels of SHS leads to sustained vascular injury characterized by mobilization of dysfunctional EPCs with blocked nitric oxide production. Our results suggest that SHS not only affects the vascular endothelium, but also the function of EPCs.

  17. Normal Functions as a New Way of Defining Computable Functions

    Directory of Open Access Journals (Sweden)

    Leszek Dubiel

    2004-01-01

    Full Text Available Report sets new method of defining computable functions. This is formalization of traditional function descriptions, so it allows to define functions in very intuitive way. Discovery of Ackermann function proved that not all functions that can be easily computed can be so easily described with Hilbert's system of recursive functions. Normal functions lack this disadvantage.

  18. Normal Functions As A New Way Of Defining Computable Functions

    Directory of Open Access Journals (Sweden)

    Leszek Dubiel

    2004-01-01

    Full Text Available Report sets new method of defining computable functions. This is formalization of traditional function descriptions, so it allows to define functions in very intuitive way. Discovery of Ackermann function proved that not all functions that can be easily computed can be so easily described with Hilbert’s system of recursive functions. Normal functions lack this disadvantage.

  19. Angiocrine functions of organ-specific endothelial cells.

    Science.gov (United States)

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

    2016-01-21

    Endothelial cells that line capillaries are not just passive conduits for delivering blood. Tissue-specific endothelium establishes specialized vascular niches that deploy sets of growth factors, known as angiocrine factors. These cues participate actively in the induction, specification, patterning and guidance of organ regeneration, as well as in the maintainance of homeostasis and metabolism. When upregulated following injury, they orchestrate self-renewal and differentiation of tissue-specific resident stem and progenitor cells into functional organs. Uncovering the mechanisms by which organotypic endothelium distributes physiological levels of angiocrine factors both spatially and temporally will lay the foundation for clinical trials that promote organ repair without scarring.

  20. [Effect of enalapril maleate on vascular endothelial function and platelet-endothelial interactions in patients with essential hypertension].

    Science.gov (United States)

    Iakovlev, V M; Semenkin, A A; Iudin, S M; Nazarov, A G; Kudriashov, I L; Potapov, V V; Korennova, O Iu; Il'iunykh, L N

    2000-01-01

    Evaluation of endothelial function and platelet-endothelial interactions in patients with essential hypertension and dynamics of these changes in the course of treatment with enalapril maleate. The study included 37 patients with essential hypertension and 22 normotensive volunteers. 17 of hypertensive patients received enalapril maleate (enap, KRKA) 5-20 mg/day during the period of 1.5 months. The complex of investigations included: measurement of total plasma cholesteroi, 12-lead ECG, echocardiography, high-resolution ultrasound investigation of brachio-cephalic arteries, evaluation of flow-mediated dilation, measurement of von Willebrand's factor, spontaneous and induced platelet aggregation. Patients with essential hypertension exhibited higher levels of von Willebrand's factor in plasma and degree of spontaneous and induced platelet aggregation as well as lower responses of vessel wall to hemodynamic stimuli compared to normotensive healthy individuals. There was a strong correlation between endothelial function markers and CAD risk factors, elevation of platelet activity. Treatment with enalapril maleate led to a statistically significant decrease of von Willebrand's factor in plasma and ex vivo platelet aggregation whereas flow-mediated dilatation increased. Values of endothelial function markers and platelet activity approached to those of normotensive subjects and these changes were accompanied by a decrease of ECG signs of left ventricular hypertrophy. Patients with essential hypertension were found to have compromised endothelial function. However, the degree of endothelial dysfunction depends not on hemodynamic parameters, but on the cumulative effect of CAD risk factors. Treatment with enalapril maleate may lead to normalisation of endothelial function and decrease of platelet activity.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. [Normal aging of frontal lobe functions].

    Science.gov (United States)

    Calso, Cristina; Besnard, Jérémy; Allain, Philippe

    2016-03-01

    Normal aging in individuals is often associated with morphological, metabolic and cognitive changes, which particularly concern the cerebral frontal regions. Starting from the "frontal lobe hypothesis of cognitive aging" (West, 1996), the present review is based on the neuroanatomical model developed by Stuss (2008), introducing four categories of frontal lobe functions: executive control, behavioural and emotional self-regulation and decision-making, energization and meta-cognitive functions. The selected studies only address the changes of one at least of these functions. The results suggest a deterioration of several cognitive frontal abilities in normal aging: flexibility, inhibition, planning, verbal fluency, implicit decision-making, second-order and affective theory of mind. Normal aging seems also to be characterised by a general reduction in processing speed observed during neuropsychological assessment (Salthouse, 1996). Nevertheless many cognitive functions remain preserved such as automatic or non-conscious inhibition, specific capacities of flexibility and first-order theory of mind. Therefore normal aging doesn't seem to be associated with a global cognitive decline but rather with a selective change in some frontal systems, conclusion which should be taken into account for designing caring programs in normal aging.

  3. Vascular expression of endothelial antigen PAL-E indicates absence of blood-ocular barriers in the normal eye

    NARCIS (Netherlands)

    Schlingemann, R. O.; Hofman, P.; Anderson, L.; Troost, D.; van der Gaag, R.

    1997-01-01

    The endothelium-specific antigen PAL-E is expressed in capillaries and veins throughout the body with the exception of the brain, where the antigen is absent from anatomical sites with a patent blood-brain barrier. In this study we determined vascular endothelial staining for PAL-E in the normal eye

  4. Barrier Functionality of Porcine and Bovine Brain Capillary Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Ailar Nakhlband

    2011-09-01

    Full Text Available Introduction: To date, isolated cell based blood-brain barrier (BBB models have been widely used for brain drug delivery and targeting, due to their relatively proper bioelectrical and permeability properties. However, primary cultures of brain capillary endothelial cells (BCECs isolated from different species vary in terms of bioelectrical and permeability properties. Methods: To pursue this, in the current investigation, primary porcine and bovine BCECs (PBCECs and BBCECs, respectively were isolated and used as an in vitro BBB model. The bioelectrical and permeability properties were assessed in BCECs co-cultured with C6 cells with/without hydrocortisone (550 nM. The bioelectrical properties were further validated by means of the permeability coefficients of transcellular and paracellular markers. Results: The primary PBCECs displayed significantly higher trans-endothelial electrical resistance (~900 W.cm2 than BBCECs (~700 W.cm2 - both co-cultured with C6 cells in presence of hydrocortisone. Permeability coefficients of propranolol/diazepam and mannitol/sucrose in PBCECs were ~21 and ~2 (×10-6 cm.sec-1, where these values for BBCECs were ~25 and ~5 (×10-6 cm.sec-1. Conclusion: Upon our bioelectrical and permeability findings, both models display discriminative barrier functionality but porcine BCECs seem to provide a better platform than bovine BCECs for drug screening and brain targeting.

  5. 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

  6. Adipokine expression and endothelial function in subclinical hypothyroidism rats

    Directory of Open Access Journals (Sweden)

    Ningning Gong

    2018-02-01

    Full Text Available The purpose of our study was to observe adipokine expression and endothelial function in subclinical hypothyroidism (sHT rats and to determine whether levothyroxine (LT4 treatment affects these changes. Sixty-five male Wistar rats were randomly divided into five groups: the control group; sHT A, B and C groups and the sHT + T4 group. The sHT rats were induced by methimazole (MMI and the sHT + T4 rats were administered LT4 treatment after 8 weeks of MMI administration. Thyroid function and lipid levels were measured using radioimmunoassays and enzymatic colorimetric methods, respectively. Serum adiponectin (APN, chemerin, TNF-α, endothelin (ET-1 and nitric oxide (NO levels were measured using ELISA kits and a nitric-reductive assay. The expression of APN, chemerin and TNF-α in visceral adipose tissue (VAT was measured in experimental rats using RT-PCR and Western blotting. Hematoxylin–eosin (HE staining was used to observe changes in adipose tissue. The sHT rats had significantly higher levels of thyroid-stimulating hormone (TSH, TNF-α, chemerin, ET-1, total cholesterol (TC and low-density lipoprotein cholesterol (LDL-C and lower levels of APN and NO than those in control and sHT + T4 rats. Based on Pearson correlation analysis, the levels of chemerin, TNF-α, ET-1, LDL-C, TC and triglyceride (TG were positively correlated with TSH, but APN and NO levels were negatively correlated with TSH. These findings demonstrated that high TSH levels contribute to the changes of adipokines and endothelial dysfunction in sHT, but LT4 treatment ameliorates those changes.

  7. Circulating Microparticles Carry a Functional Endothelial Nitric Oxide Synthase That Is Decreased in Patients With Endothelial Dysfunction

    Science.gov (United States)

    Horn, Patrick; Cortese‐Krott, Miriam Margherita; Amabile, Nicolas; Hundsdörfer, Claas; Kröncke, Klaus‐Dietrich; Kelm, Malte; Heiss, Christian

    2013-01-01

    Background Microparticles (MPs) are circulating membrane particles of less than a micrometer in diameter shed from endothelial and blood cells. Recent literature suggests that MPs are not just functionally inert cell debris but may possess biological functions and mediate the communication between vascular cells. As a significant proportion of MPs originate from platelets and endothelial cells, we hypothesized that MPs may harbor functional enzymes including an endothelial NO synthase (eNOS). Methods and Results Using immunoprecipitation and Western blot analysis, we found that human circulating MPs carry an eNOS. Ca2+ and l‐arginine‐dependent NOS activity of crude enzyme extract from MPs was determined by measuring the conversion of [3H]‐L‐arginine to [3H]‐citrulline and NOS‐dependent nitrite production. NOS‐dependent NO production in intact MPs was assessed by the NO‐specific fluorescent probe MNIP‐Cu. In patients with cardiovascular disease, endothelial dysfunction was associated with an increase in the total number of circulating MPs as well as a significant decrease in the expression and activity of eNOS in MPs. No difference in reactive oxygen species was noted in MPs isolated from either group. Conclusions Our data further support the concept that circulating MPs may not only retain phenotypic markers but also preserve the functionality of enzymes of the cells they originate from, including eNOS. PMID:23525410

  8. Enhancer-associated long non-coding RNA LEENE regulates endothelial nitric oxide synthase and endothelial function.

    Science.gov (United States)

    Miao, Yifei; Ajami, Nassim E; Huang, Tse-Shun; Lin, Feng-Mao; Lou, Chih-Hong; Wang, Yun-Ting; Li, Shuai; Kang, Jian; Munkacsi, Hannah; Maurya, Mano R; Gupta, Shakti; Chien, Shu; Subramaniam, Shankar; Chen, Zhen

    2018-01-18

    The optimal expression of endothelial nitric oxide synthase (eNOS), the hallmark of endothelial homeostasis, is vital to vascular function. Dynamically regulated by various stimuli, eNOS expression is modulated at transcriptional, post-transcriptional, and post-translational levels. However, epigenetic modulations of eNOS, particularly through long non-coding RNAs (lncRNAs) and chromatin remodeling, remain to be explored. Here we identify an enhancer-associated lncRNA that enhances eNOS expression (LEENE). Combining RNA-sequencing and chromatin conformation capture methods, we demonstrate that LEENE is co-regulated with eNOS and that its enhancer resides in proximity to eNOS promoter in endothelial cells (ECs). Gain- and Loss-of-function of LEENE differentially regulate eNOS expression and EC function. Mechanistically, LEENE facilitates the recruitment of RNA Pol II to the eNOS promoter to enhance eNOS nascent RNA transcription. Our findings unravel a new layer in eNOS regulation and provide novel insights into cardiovascular regulation involving endothelial function.

  9. Effect of vitamin D on endothelial progenitor cells function.

    Directory of Open Access Journals (Sweden)

    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.

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

    OpenAIRE

    Silva, Carlos Alberto da; Lopes Vasconcelos-Filho, Francisco Sérgio; Serafim, Marcus; Botura, Edson; Rocha-e-Silva, Roberta Cristina da; Pacheco, Christina; Marques, Fernando Antônio Oliveira; Melo, Sebastião Iberes Lopes

    2016-01-01

    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...

  11. Decreased endothelial nitric oxide synthase expression and function contribute to impaired mitochondrial biogenesis and oxidative stress in fetal lambs with persistent pulmonary hypertension

    OpenAIRE

    Afolayan, Adeleye J.; Eis, Annie; Alexander, Maxwell; Michalkiewicz, Teresa; Teng, Ru-Jeng; Lakshminrusimha, Satyan; Konduri, Girija G.

    2015-01-01

    Impaired vasodilation in persistent pulmonary hypertension of the newborn (PPHN) is characterized by mitochondrial dysfunction. We investigated the hypothesis that a decreased endothelial nitric oxide synthase level leads to impaired mitochondrial biogenesis and function in a lamb model of PPHN induced by prenatal ductus arteriosus constriction. We ventilated PPHN lambs with 100% O2 alone or with inhaled nitric oxide (iNO). We treated pulmonary artery endothelial cells (PAECs) from normal and...

  12. Vascular expression of endothelial antigen PAL-E indicates absence of blood-ocular barriers in the normal eye.

    Science.gov (United States)

    Schlingemann, R O; Hofman, P; Anderson, L; Troost, D; van der Gaag, R

    1997-01-01

    The endothelium-specific antigen PAL-E is expressed in capillaries and veins throughout the body with the exception of the brain, where the antigen is absent from anatomical sites with a patent blood-brain barrier. In this study we determined vascular endothelial staining for PAL-E in the normal eye in relation to the ocular blood-tissue barriers. Immunohistochemical staining of frozen tissue sections of eyes from 22 cornea donors and a number of normal animal autopsy eyes was performed for the PAL-E antigen and the blood-brain barrier marker glucose transporter 1. In normal human and animal eyes, endothelial PAL-E staining was absent from the microvasculature in iris, ciliary muscle, optic nerve and retina. In a few normal human eyes, some weakly stained capillaries were observed in the retina and nerve fiber layer, mostly in the peripapillary area. Marked staining of capillaries and venules with PAL-E was observed in the conjunctiva, episclera, sclera, ciliary processes, choriocapillaris and optic nerve head. In general, the endothelial antigen PAL-E is absent from microvessels involved in the blood-ocular and the blood-retinal barriers. PAL-E may therefore be a useful marker to identify pathological breakdown of blood-ocular barriers.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Functional and gene expression analysis of hTERT overexpressed endothelial cells

    Directory of Open Access Journals (Sweden)

    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

  15. Cognitive functions and normal tension glaucoma.

    Science.gov (United States)

    Daveckaite, Akvile; Grusauskiene, Evelina; Petrikonis, Kestutis; Vaitkus, Antanas; Siaudvytyte, Lina; Januleviciene, Ingrida

    2017-10-01

    Only a few studies have analyzed the potential link between glaucoma and cognitive function impairment. They have found controversial results. This study aims to perform quick cognitive function assessment with clock drawing test (CDT) using two different scoring systems and compare between normal tension glaucoma (NTG) and cataract patients. Totally, 30 NTG and 30 patients with cataracts were included in a prospective, pilot study. The predrawn circle was given, and patients were asked to draw the clock showing a time of 11:10. The test was evaluated using two methods - Freund method using a 7-point scoring scale (optimal cutoff ≤4) and Rakusa using a 4-point scoring scale (optimal cutoff ≤3). The level of significance was set at P drawing. Further prospective studies are needed to investigate the CDT reliability as fast screening test of cognitive function impairment in glaucoma patients.

  16. Effects of amlodipine on endothelial function in rats with chronic heart failure after experimental myocardial infarction

    NARCIS (Netherlands)

    deVries, RJM; Anthonio, R; vanVeldhuisen, DJ; Buikema, H; vanGilst, WH

    1997-01-01

    In chronic heart failure, the role of endothelial dysfunction is not yet well established. As calcium metabolism plays an important role in the endothelium, it might be suggested that calcium channel blockers influence endothelial function. Although calcium channel blockers are generally

  17. GPER Mediates Functional Endothelial Aging in Renal Arteries.

    Science.gov (United States)

    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.

  18. Normal erect swallowing. Normal function and incidence of variations.

    Science.gov (United States)

    Curtis, D J; Cruess, D F; Dachman, A H

    1985-10-01

    Of 871 candidates presenting for upper gastrointestinal examinations, 16 met the rigorous criteria established for selecting asymptomatic normal volunteers. Frame-by-frame evaluation of their videorecorded pharyngeal swallow confirmed many observations made previously utilizing cine recording at much higher radiation dosages. In addition, new observations were made: the nasopharynx may not occlude until the bolus is entirely within the pharynx; air mixes with the bolus if the swallow is an "open" type; the epiglottis always inverts in normal individuals regardless of the type of swallow ("open," air filled oro-and hypopharynx into which the swallowed bolus is dropped; "closed," airless oropharynx into which the swallowed bolus is pushed by a continuous peristaltic drive of the tongue and palate, thus reconstituting the pharyngeal space); laryngeal descent may aid in stripping the bolus from the pharynx; the vestibule may not completely close during the swallow and the larynx can still be impervious to the bolus; the peristaltic wave does not begin until the bolus has breeched the cricopharyngeus; the cricopharyngeus may be seen frequently in normal individuals, but does not delay the passage of the bolus; asymmetric flow of the bolus around the larynx is common and may not be the result of epiglottic tilt or head positioning.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. Contact lens-induced corneal endothelial polymegathism: functional significance and possible mechanisms.

    Science.gov (United States)

    Connor, C G; Zagrod, M E

    1986-07-01

    The corneal endothelium is principally responsible for maintenance of corneal deturgescence. Therefore, compromise of corneal endothelial functional integrity can result in corneal swelling and opacification. Contact lenses constitute a potential insult to the cornea because their wear reduces the oxygen available to that tissue. It has been reported that contact lens wear induces transient as well as permanent morphologic changes in the corneal endothelium. One of the permanent changes reported is referred to as polymegathism, which is a variation in cell size within the endothelial monolayer. Several investigators have suggested that polymegathism reflects a compromised endothelial functional status. Mechanisms proposed to explain contact lens-induced polymegathism include lactate accumulation, changes in pH, and elevation in CO2 content. We discuss these possibilities as well as speculate that these polymegathous shape changes may be a result of decreased endothelial ATP (adenosine triphosphate) levels and disturbed calcium homeostasis due to corneal endothelial hypoxia.

  1. 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

  2. Endothelial function in children with a history of henoch schonlein purpura.

    Science.gov (United States)

    Butbul Aviel, Yonatan; Dafna, Lotem; Pilar, Giora; Brik, Riva

    2017-01-14

    Although Henoch-Schonlein purpura (HSP) is the most common form of systemic vasculitis in children, the long term effect of HSP on endothelial function is still not clear. The aim of our study was to evaluate the long term effect of HSP on endothelial function in children and adolescents. This research was an observational prospective study. The study group comprised of 19 children diagnosed with HSP. The minimum interval between the diagnosis with HSP and endothelial testing was 5 months. Endothelial function evaluation was assessed by a noninvasive technology named peripheral arterial tonometry, using an EndoPAT™ device. This method measures blood flow in the limb, in response to arterial occlusion, and calculates a Reactive Hyperemic Index (RHI) as an index of endothelial function. RHI values of the study group were compared to those of a known control group. Nineteen children and adolescents with HSP underwent endothelial function studies. Endothelial function was compared to that of a known control group comprising of 23 healthy children and adolescents. The two groups had similar characteristics, including age, male to female ratio, height, weight and BMI. Mean RHI was 1.81 in the study group, and 1.87 in the control group (p = 0.18). Linear regression of the study group, showed a positive correlation between the time interval from HSP diagnosis to participation in the study, and between the RHI value (r = 0.542, p = 0.016). RHI levels were significantly higher in patients who had endothelial function measured more than 6 years since the diagnosis of HSP compared with those patients with less than 6 years follow up (1.98 + 0.74 vs. 1.38 ± 0.43 P = 0.037). These results suggest that HSP causes short term endothelial dysfunction that improves with time.

  3. Endothelial function in youth: A biomarker modulated by adiposity-related insulin resistance

    Science.gov (United States)

    To investigate the physical and metabolic determinants of endothelial dysfunction, an early marker of subclinical atherosclerosis, in normal weight and overweight adolescents with and without type 2 diabetes mellitus. A cross-sectional study of 81 adolescents: 21 normal weight, 25 overweight with no...

  4. Exercise training normalizes skeletal muscle vascular endothelial growth factor levels in patients with essential hypertension

    DEFF Research Database (Denmark)

    Hansen, Ane Håkansson; Nielsen, Jens Jung; Saltin, Bengt

    2010-01-01

    METHODS: Vascular endothelial growth factor (VEGF) protein and capillarization were determined in muscle vastus lateralis biopsy samples in individuals with essential hypertension (n = 10) and normotensive controls (n = 10). The hypertensive individuals performed exercise training for 16 weeks....... Muscle samples as well as muscle microdialysis fluid samples were obtained at rest, during and after an acute exercise bout, performed prior to and after the training period, for the determination of muscle VEGF levels, VEGF release, endothelial cell proliferative effect and capillarization. RESULTS......: Prior to training, the hypertensive individuals had 36% lower levels of VEGF protein and 22% lower capillary density in the muscle compared to controls. Training in the hypertensive group reduced (P

  5. AVE3085, an enhancer of endothelial nitric oxide synthase, restores endothelial function and reduces blood pressure in spontaneously hypertensive rats

    Science.gov (United States)

    Yang, Qin; Xue, Hong-Mei; Wong, Wing-Tak; Tian, Xiao-Yu; Huang, Yu; Tsui, Stephen KW; Ng, Patrick KS; Wohlfart, Paulus; Li, Huige; Xia, Ning; Tobias, Silke; Underwood, Malcolm John; He, Guo-Wei

    2011-01-01

    BACKGROUND AND PURPOSE Nitric oxide (NO) plays an important role in endothelial function, and impaired NO production is involved in hypertension. Therefore, compounds that regulate endothelial NO synthase (eNOS) may be of therapeutic benefit. A novel, low molecular weight compound AVE3085 is a recently developed compound with the ability to enhance eNOS transcription. The present study investigated the effects of AVE3085 in endothelial dysfunction associated with hypertension. EXPERIMENTAL APPROACH Spontaneously hypertensive rats (SHRs) were treated with AVE 3085 (10 mg·kg·day−1, orally) for 4 weeks. Isometric force measurement was performed on rings of isolated aortae in organ baths. Protein expression of eNOS, phosphorylated-eNOS and nitrotyrosine in the aortae were examined by Western blotting. mRNA for eNOS in rat aortae were examined by reverse-transcriptase polymerase chain reaction (RT-PCR). KEY RESULTS AVE3085 greatly improved endothelium-dependent relaxations in the aortae of SHRs. This functional change was accompanied by up-regulated expression of eNOS protein and mRNA, enhanced eNOS phosphorylation and decreased formation of nitrotyrosine. Furthermore, AVE3085 treatment reduced the blood pressure in SHR without affecting that of hypertensive eNOS−/− mice. CONCLUSIONS AND IMPLICATIONS The eNOS-transcription enhancer AVE3085 restored impaired endothelial function in a hypertensive model. The present study provides a solid basis for the potential development of eNOS-targeting drugs to restore down-regulated eNOS, as a new strategy in hypertension. PMID:21385179

  6. Presentation of myelin basic protein by normal guinea-pig brain endothelial cells and its relevance to experimental allergic encephalomyelitis.

    Science.gov (United States)

    Wilcox, C E; Healey, D G; Baker, D; Willoughby, D A; Turk, J L

    1989-08-01

    Previous studies have shown that endothelial cells in the central nervous system (CNS) of normal guinea-pigs constitutively express certain MHC class II determinants, whilst the expression of other determinants is apparent during the acute phase of chronic relapsing experimental allergic encephalomyelitis (CREAE). The expression of MHC class II determinants is retained by endothelial cells derived from normal guinea-pig brain tissue and maintained in culture. This present study demonstrates that the MHC class II molecules on these cells can be recognized by allogeneic lymphocytes, resulting in a proliferative response which is enhanced by the addition of exogenous IL-2. The endothelial cells were incapable of presenting either purified protein derivative or ovalbumin, but they could present autologous myelin basic protein (MBP), an encephalitogen implicated in the pathogenesis of EAE. The resulting lymphocyte proliferative response was of the same magnitude as that obtained when a control population of macrophages was used to present MBP. These results, therefore, suggest that cerebrovascular endothelia have the potential to play a role in the pathogenesis of EAE.

  7. 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.

  8. Influence of ethnic background on left atrial markers of inflammation, endothelial function and tissue remodelling

    Directory of Open Access Journals (Sweden)

    Carlee D. Ruediger

    2018-01-01

    Conclusion: Caucasian and Indian populations demonstrate similar inflammatory, endothelial function or tissue remodelling profiles. This study suggests a lack of an impact of different ethnicity in these populations in terms of thrombogenic risk.

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

    Science.gov (United States)

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

    2017-06-01

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

  10. Physiological changes in blood pressure impact peripheral endothelial function during adolescence.

    Science.gov (United States)

    Deda, Livia; Sochett, Etienne B; Mahmud, Farid H

    2015-04-01

    Reactive hyperemia index is a measure of endothelial function used to assess subclinical atherosclerosis. When evaluated in healthy adolescents, significant changes in endothelial function were correlated with advancing age, pubertal status, and blood pressure. Blood pressure was the principal contributor to reactive hyperemia index variability independent of age, lipid profile, body mass index, and/or pubertal status. Interpretation of this peripheral vascular marker should include age and maturational changes in paediatric patients.

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

    Science.gov (United States)

    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.

  12. Evaluation of the EndoPAT as a Tool to Assess Endothelial Function

    Directory of Open Access Journals (Sweden)

    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.

  13. Laminar shear stress regulates endothelial kinin B1 receptor expression and function: potential implication in atherogenesis

    Science.gov (United States)

    Duchene, Johan; Cayla, Cécile; Vessillier, Sandrine; Scotland, Ramona; Yamashiro, Kazuo; Lecomte, Florence; Syed, Irfan; Vo, Phuong; Marrelli, Alessandra; Pitzalis, Costantino; Cipollone, Francesco; Schanstra, Joost; Bascands, Jean-Loup; Hobbs, Adrian J; Perretti, Mauro; Ahluwalia, Amrita

    2009-01-01

    OBJECTIVE The pro-inflammatory phenotype induced by low laminar shear stress (LSS) is implicated in atherogenesis. The kinin B1 receptor (B1R), known to be induced by inflammatory stimuli, exerts many pro-inflammatory effects including vasodilatation and leukocyte recruitment. We investigated whether low LSS is a stimulus for endothelial B1R expression and function. METHODS AND RESULTS Human and mouse atherosclerotic plaques expressed high level of B1R mRNA and protein. In addition, B1R expression was upregulated in the aortic arch (low LSS region) of ApoE-/- mice fed a high fat diet compared to vascular regions of high LSS and animals fed normal chow. Of interest, a greater expression of B1R was noticed in endothelial cells from regions of low LSS in aortic arch of ApoE-/- mice. B1R was also upregulated in human umbilical vein endothelial cells (HUVEC) exposed to low LSS (0-2dyn/cm2) compared to physiological LSS (6-10dyn/cm2): an effect similarly evident in murine vascular tissue perfused ex vivo. Functionally, B1R activation increased prostaglandin and CXCL5 expression in cells exposed to low, but not physiological, LSS. IL-1β and ox-LDL induced B1R expression and function in HUVECs, a response substantially enhanced under low LSS conditions and inhibited by blockade of NFκB activation. CONCLUSION Herein, we show that LSS is a major determinant of functional B1R expression in endothelium. Furthermore, whilst physiological high LSS is a powerful repressor of this inflammatory receptor, low LSS at sites of atheroma are associated with substantial upregulation, identifying this receptor as a potential therapeutic target. CONDENSED ABSTRACT Low laminar shear stress (LSS) underlies the pro-inflammatory processes in atherogenesis. Herein, we demonstrate that whilst physiological LSS represses inflammatory kinin B1 receptor (B1R) expression/function, low atherogenic LSS is associated with profound upregulation of both in atherosclerosis in both humans and animal

  14. Fo Shou San, an ancient Chinese herbal decoction, protects endothelial function through increasing endothelial nitric oxide synthase activity.

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    Cathy W C Bi

    Full Text Available Fo Shou San (FSS is an ancient herbal decoction comprised of Chuanxiong Rhizoma (CR; Chuanxiong and Angelicae Sinensis Radix (ASR; Danggui in a ratio of 2:3. Previous studies indicate that FSS promotes blood circulation and dissipates blood stasis, thus which is being used widely to treat vascular diseases. Here, we aim to determine the cellular mechanism for the vascular benefit of FSS. The treatment of FSS reversed homocysteine-induced impairment of acetylcholine (ACh-evoked endothelium-dependent relaxation in aortic rings, isolated from rats. Like radical oxygen species (ROS scavenger tempol, FSS attenuated homocysteine-stimulated ROS generation in cultured human umbilical vein endothelial cells (HUVECs, and it also stimulated the production of nitric oxide (NO as measured by fluorescence dye and biochemical assay. In addition, the phosphorylation levels of both Akt kinase and endothelial NO synthases (eNOS were markedly increased by FSS treatment, which was abolished by an Akt inhibitor triciribine. Likewise, triciribine reversed FSS-induced NO production in HUVECs. Finally, FSS elevated intracellular Ca(2+ levels in HUVECs, and the Ca(2+ chelator BAPTA-AM inhibited the FSS-stimulated eNOS phosphorylation. The present results show that this ancient herbal decoction benefits endothelial function through increased activity of Akt kinase and eNOS; this effect is causally via a rise of intracellular Ca(2+ and a reduction of ROS.

  15. Cognitive functions and normal tension glaucoma

    Directory of Open Access Journals (Sweden)

    Akvile Daveckaite

    2017-01-01

    Full Text Available Purpose: Only a few studies have analyzed the potential link between glaucoma and cognitive function impairment. They have found controversial results. This study aims to perform quick cognitive function assessment with clock drawing test (CDT using two different scoring systems and compare between normal tension glaucoma (NTG and cataract patients. Methods: Totally, 30 NTG and 30 patients with cataracts were included in a prospective, pilot study. The predrawn circle was given, and patients were asked to draw the clock showing a time of 11:10. The test was evaluated using two methods – Freund method using a 7-point scoring scale (optimal cutoff ≤4 and Rakusa using a 4-point scoring scale (optimal cutoff ≤3. The level of significance was set at P < 0.05. Results: CDT result was significantly better in cataract group than in NTG group: 3.5 (2 versus 2 (2 by Freund, (P = 0.003 and 6.5 (1 versus 4.5 (2.75 by Rakusa, respectively (P = 0.004. Sixty percent (n = 18 of NTG group and 10% (n = 3 of cataract group patients completed the CDT in the specific picture manner (the short hand on 11 and the long hand between 11 and 12, (P = 0.001. Conclusions: Lower CDT results were seen in NTG patients according to two different scoring systems. NTG patients showed a specific manner of drawing. Further prospective studies are needed to investigate the CDT reliability as fast screening test of cognitive function impairment in glaucoma patients.

  16. Effects of different degrees of insulin sensitivity on endothelial function in obese patients.

    Science.gov (United States)

    Galvão, Roberto; Plavnik, Frida Liane; Ribeiro, Fernando Flexa; Ajzen, Sérgio Aron; Christofalo, Dejaldo M de J; Kohlmann, Osvaldo

    2012-01-01

    Obesity derived from intra-abdominal fat deposition tends to increase hormonal and cytokine production, thus worsening insulin sensitivity and leading to endothelial dysfunction. Hyperinsulinemia is considered an independent risk factor for ischemic heart disease and cause of endothelial dysfunction in healthy individuals. To assess the impact of different degrees of insulin resistance, measured by HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), on endothelial function in obese, non-diabetic patients without prior history of cardiovascular events and different metabolic syndrome components. Forty obese individuals were submitted to anthropometric measurements, BP measurements at office and ABPM and laboratory tests, in addition to non-invasive ultrasound assessment of endothelial function. Patients were divided into 3 groups according to the level of insulin resistance: patients with HOMA-IR values from 0.590 to 1.082 were assigned to Group 1 (n=13), from 1.083 to 1.410 to Group 2 (n=14) and from 1.610 to 2.510 to Group 3 (n=13). We found a significant difference in flow-mediated dilation in group 3 compared to group 1 (9.2 ± 7.0 vs 18.0 ± 7.5 %, p=0.006). There was a negative correlation between endothelial function and insulin, HOMA-IR and triglycerides. Our data suggest that mild changes in insulin resistance levels assessed by HOMA-IR may have an impact on vasodilatatory endothelial function in uncomplicated obese individuals with different cardiovascular risk factors.

  17. Cardiovascular risk factors and systemic endothelial function in patients with cirrhosis.

    Science.gov (United States)

    Berzigotti, Annalisa; Erice, Eva; Gilabert, Rosa; Reverter, Enric; Abraldes, Juan G; García-Pagan, Juan Carlos; Bosch, Jaime

    2013-01-01

    Cardiovascular risk factors (CVRF) lead to systemic endothelial dysfunction. It has been suggested that in cirrhosis, cardiovascular risk is low and systemic endothelial function is enhanced. However, there is no prospective study evaluating the relationship between cardiovascular risk and systemic endothelial function in cirrhosis, which was investigated here. In 47 patients with cirrhosis (33 males; median Child-Pugh score 8; median age 55 years), we evaluated: laboratory parameters, hepatic and systemic hemodynamics, CVRF, 10-year global cardiovascular risk by Framingham score, and presence of carotid plaques. Systemic endothelial dysfunction was investigated non-invasively by flow-mediated dilatation (FMD) of the brachial artery by ultrasound and defined as FMD risk (median 7%) was low in 25%, moderate in 26%, moderately high in 40%, and high in 9%. Fifty-three percent of patients had systemic endothelial dysfunction. Systemic endothelial dysfunction (low FMD) increased in parallel with CV risk (linear trend P=0.039) and was higher in patients overweight or obese. Conversely, FMD increased in parallel with Child-Pugh/Mayo Clinic Model for End-stage Liver Disease (MELD) score, bilirubin, serum sodium, plasma renin activity, leukocyte count, platelet count, and with lower arterial pressure, suggesting that enhanced FMD is a feature of advanced liver failure and inflammation. Cardiovascular risk, bilirubin, leukocyte count, and arterial pressure remained independently associated with systemic endothelial dysfunction. CV risk was not low in our studied patients with cirrhosis, and systemic endothelial dysfunction was frequent in this population. In cirrhosis, similar to general population, cardiovascular risk impaired systemic FMD, although liver failure attenuated endothelial dysfunction.

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

    Science.gov (United States)

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

    2018-02-01

    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.

  19. Omega-3 fatty acids plus rosuvastatin improves endothelial function in South Asians with dyslipidemia

    OpenAIRE

    Mindrescu, Catalin; Gupta, Rakesh P; Hermance, Eileen V; DeVoe, Mary C; Soma, Vikas R; Coppola, John T; Staniloae, Cezar S

    2008-01-01

    Background: The present study was undertaken to investigate the effect of statins plus omega-3 polyunsaturated fatty acids (PUFAs) on endothelial function and lipid profile in South Asians with dyslipidemia and endothelial dysfunction, a population at high risk for premature coronary artery disease. Methods: Thirty subjects were randomized to rosuvastatin 10 mg and omega-3-PUFAs 4 g or rosuvastatin 10 mg. After 4 weeks, omega-3-PUFAs were removed from the first group and added to subjects in ...

  20. Normal Function of the Colon and Anorectal Area

    Science.gov (United States)

    ... IFFGD What is Constipation Introduction: What is Constipation? Normal Function Common Questions & Mistaken Beliefs Signs & Symptoms Symptoms ... IFFGD What is Constipation Introduction: What is Constipation? Normal Function Common Questions & Mistaken Beliefs Signs & Symptoms Symptoms ...

  1. Cerebral Endothelial Function Determined by Cerebrovascular Reactivity to L-Arginine

    Science.gov (United States)

    Pretnar-Oblak, Janja

    2014-01-01

    Endothelium forms the inner cellular lining of blood vessels and plays an important role in many physiological functions including the control of vasomotor tone. Cerebral endothelium is probably one of the most specific types but until recently it was impossible to determine its function. In this review, the role of cerebrovascular reactivity to L-arginine (CVR-L-Arg) for assessment of cerebral endothelial function is discussed. L-Arginine induces vasodilatation through enhanced production of nitric oxide (NO) in the cerebral endothelium. Transcranial Doppler sonography is used for evaluation of cerebral blood flow changes. The method is noninvasive, inexpensive, and enables reproducible measurements. CVR-L-Arg has been compared to flow-mediated dilatation as a gold standard for systemic endothelial function and intima-media thickness as a marker for morphological changes. However, it seems to show specific cerebral endothelial function. So far CVR-L-Arg has been used to study cerebral endothelial function in many pathological conditions such as stroke, migraine, etc. In addition CVR-L-Arg has also proven its usefulness in order to show potential improvement after pharmacological interventions. In conclusion CVR-L-Arg is a promising noninvasive research method that could provide means for evaluation of cerebral endothelial function in physiological and pathological conditions. PMID:24860826

  2. The effects of Secondhand Smoke (SHS) exposure on microvascular endothelial function among healthy women.

    Science.gov (United States)

    Sanip, Zulkefli; Hanaffi, Siti Hajar Mohd; Ahmad, Imran; Yusoff, Siti Suhaila Mohd; Rasool, Aida Hanum Ghulam; Yusoff, Harmy Mohamed

    2015-01-01

    Studies have demonstrated that secondhand smoke (SHS) exposure could impair endothelial function. However, the effect of SHS exposure specifically on microvascular endothelial function is not well understood. This study aimed to determine the effects of SHS exposure on microvascular endothelial function among non-smoking, generally healthy women. We studied 127 women; and based on their hair nicotine levels measured using gas chromatography-mass spectrometry, 25 of them were categorized as having higher hair nicotine levels, 25 were grouped as having lower hair nicotine and 77 women were grouped into the non-detected group. The non-detected group did not have detectable levels of hair nicotine. Anthropometry, blood pressure (BP), lipid profile and high-sensitivity C-reactive protein (hsCRP) were measured accordingly. Microvascular endothelial function was assessed non-invasively using laser Doppler fluximetry and the process of iontophoresis involving acetylcholine and sodium nitroprusside as endothelium-dependent and endothelium-independent vasodilators respectively. The mean hair nicotine levels for higher and lower hair nicotine groups were 0.74 (1.04) and 0.05 (0.01) ng/mg respectively. There were no significant differences in anthropometry, BP, lipid profile and hsCRP between these groups. There were also no significant differences in the microvascular perfusion and endothelial function between these groups. In this study, generally healthy non-smoking women who have higher, lower and non-detected hair nicotine levels did not show significant differences in their microvascular endothelial function. Low levels of SHS exposure among generally healthy non-smoking women may not significantly impair their microvascular endothelial function.

  3. Ruthenium Complex Improves the Endothelial Function in Aortic Rings From Hypertensive Rats

    Science.gov (United States)

    Vatanabe, Izabela Pereira; Rodrigues, Carla Nascimento dos Santos; Buzinari, Tereza Cristina; de Moraes, Thiago Francisco; da Silva, Roberto Santana; Rodrigues, Gerson Jhonatan

    2017-01-01

    Background The endothelium is a monolayer of cells that extends on the vascular inner surface, responsible for the modulation of vascular tone. By means of the release of nitric oxide (NO), the endothelium has an important protective function against cardiovascular diseases. Objective Verify if cis- [Ru(bpy)2(NO2)(NO)](PF6)2 (BPY) improves endothelial function and the sensibility of conductance (aorta) and resistance (coronary) to vascular relaxation induced by BPY. Methods Normotensive (2K) and hypertensive (2K-1C) Wistar rats were used. For vascular reactivity study, thoracic aortas were isolated, rings with intact endothelium were incubated with: BPY(0.01 to10 µM) and concentration effect curves to acetylcholine were performed. In addition, cumulative concentration curves were performed to BPY (1.0 nM to 0.1 µM) in aortic and coronary rings, with intact and denuded endothelium. Results In aorta from 2K-1C animals, the treatment with BPY 0.1µM increased the potency of acetylcholine-induced relaxation and it was able to revert the endothelial dysfunction. The presence of the endothelium did not modify the effect of BPY in inducing the relaxation in aortas from 2K and 2K-1C rats. In coronary, the endothelium potentiated the vasodilator effect of BPY in vessels from 2K and 2K-1C rats. Conclusion Our results suggest that 0.1 µM of BPY is able to normalize the relaxation endothelium dependent in hypertensive rats, and the compound BPY induces relaxation in aortic from normotensive and hypertensive rats with the same potency. The endothelium potentiate the relaxation effect induced by BPY in coronary from normotensive and hypertensive rats, with lower effect on coronary from hypertensive rats. PMID:28678930

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

    Science.gov (United States)

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

    2015-02-24

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

  5. Effect of brief secondhand smoke exposure on endothelial function and circulating markers of inflammation.

    Science.gov (United States)

    Bonetti, Piero O; Lardi, Elena; Geissmann, Christa; Kuhn, Max U; Brüesch, Hermann; Reinhart, Walter H

    2011-03-01

    In contrast to the well defined detrimental consequences of long-term secondhand smoke (SHS) exposure, little is known about the acute effects of passive smoking on endothelial function and inflammation. The aim of the present study was to assess the acute effects of short-term SHS exposure on endothelial function and circulating markers of inflammation. Peripheral microvascular endothelial function assessed by reactive hyperemia peripheral arterial tonometry (RH-PAT) index, circulating markers of endothelial function (von Willebrand factor antigen, Thrombomodulin, E-selectin) and circulating inflammatory markers (high sensitivity C-reactive protein (hsCRP), Interleukin-6 (IL-6)) were measured in eighteen male, non-smoking volunteers before and 12h after a 1-h SHS exposure. Twelve hours after passive smoking, average RH-PAT index was significantly lower than before SHS exposure (1.54±0.49 vs 2.01±0.55 (mean±SD), p=0.01) indicating deterioration of peripheral microvascular endothelial function. von Willebrand factor antigen as a marker of endothelial activation was significantly increased after SHS exposure (93.0±25.5% vs 78.4±17.9%, p=0.03). Levels of Thrombomodulin, E-selectin, hsCRP, and IL-6 were unaffected by SHS exposure. Short-term SHS exposure leads to a measurable disturbance of endothelial function. However, 1h of passive smoking appears to be too short to elicit a significant inflammatory response. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  6. Role of Vascular Endothelial Growth Factor (VEGF) in Thymus of Mice under Normal Conditions and with Tumor Growth.

    Science.gov (United States)

    Kisseleva, E P; Krylov, A V; Lyamina, I V; Kudryavtsev, I V; Lioudyno, V I

    2016-05-01

    In our study, we for the first time investigated a role for VEGF as a factor regulating transendothelial migration of murine thymocytes in vitro. Effects of VEGF were examined in a model of thymocyte migration across a monolayer of EA.hy 926 endothelial cells. We showed that VEGF enhanced transendothelial migration of murine thymocytes and their adhesion to endothelial cells in a dose-dependent manner. VEGF did not influence thymocytes, but rather acted on endothelial cells by upregulating surface expression of adhesion molecule ICAM-1 and downregulating activity of 5'-nucleotidase. Effects from VEGF were comparable with those from TNF-α. Because it is known that administration of VEGF to intact animals results in thymic atrophy, it was assumed that it might play a role in developing thymic involution during tumor growth. Enhanced egress of thymocytes to the periphery was considered as a plausible mechanism underlying effects of VEGF. However, we revealed no difference in parameters of in vitro transendothelial migration for thymocytes from animals bearing a transplantable hepatoma 22a compared to control animals. VEGF mRNA expression in lysates of thymic stroma was found to be upregulated in mice with grafted tumors, whereas at the protein level the amount of VEGF did not differ. While examining expression of VEGF receptors on thymocytes by flow cytometry, both VEGFR-1 and VEGFR-2 were not detected, whereas the percentage of Nrp-1-positive thymocytes in animals with hepatoma 22a was as high as in the control group. Thus, we were unable to confirm a hypothesis regarding participation of VEGF in developing thymic involution during progression of experimental hepatoma. However, a set of novel data concerning a role for VEGF in stimulating transendothelial migration of thymocytes in vitro was obtained, and it may be of significance for understanding mechanisms underlying thymus functioning as well as a role of this cytokine in preparing endothelial cells for egress

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  9. Endothelial and beta cell composite aggregates for improved function of a bioartificial pancreas encapsulation device.

    Science.gov (United States)

    Skrzypek, Katarzyna; Barrera, Yazmin Brito; Groth, Thomas; Stamatialis, Dimitrios

    2018-03-01

    Encapsulation of pancreatic islets or beta cells is a promising strategy for treatment of type 1 diabetes by providing an immune isolated environment and allowing for transplantation in a different location than the liver. However, islets used for encapsulation often show lower functionality due to the damaging of islet endothelial cells during the isolation procedure. Factors produced by endothelial cells have great impact on beta cell insulin secretion. Therefore, mutual signaling between endothelial cells and beta cells should be considered for the development of encapsulation systems to achieve high insulin secretion and maintain beta cell viability. Here, we investigate whether co-culture of beta cells with endothelial cells could improve beta cell function within encapsulation devices. Mouse insulinoma MIN6 cells and human umbilical vein endothelial cells were used for creating composite aggregates on agarose microwell platform. The composite aggregates were encapsulated within flat poly(ether sulfone)/polyvinylpyrrolidone device. Their functionality was assessed by glucose-induced insulin secretion test and compared to non-encapsulated free-floating aggregates. We created composite aggregates of 80-100 µm in diameter, closely mimicking pancreatic islets. Upon glucose stimulation, their insulin secretion is improved in comparison to aggregates consisting of only MIN6 cells. Moreover, the composite aggregates encapsulated within a device secrete more insulin than aggregates consisting of only MIN6 cells. Composite aggregates of MIN6 cells with human umbilical vein endothelial cells have improved insulin secretion in comparison to MIN6 aggregates showing that the interaction of beta cell and endothelial cell is crucial for a functional encapsulation system.

  10. Molecular and functional characterization of riboflavin specific transport system in rat brain capillary endothelial cells

    Science.gov (United States)

    Patel, Mitesh; Vadlapatla, Ramya Krishna; Pal, Dhananjay; Mitra, Ashim K.

    2012-01-01

    Riboflavin is an important water soluble vitamin (B2) required for metabolic reactions, normal cellular growth, differentiation and function. Mammalian brain cells cannot synthesize riboflavin and must import from systemic circulation. However, the uptake mechanism, cellular translocation and intracellular trafficking of riboflavin in brain capillary endothelial cells are poorly understood. The primary objective of this study is to investigate the existence of riboflavin-specific transport system and delineate the uptake and intracellular regulation of riboflavin in immortalized rat brain capillary endothelial cells (RBE4). The uptake of [3H]-Riboflavin is sodium, temperature and energy dependent but pH independent. [3H]-Riboflavin uptake is saturable with Km and Vmax values of 19 ± 3 µM and 0.235 ± 0.012 picomoles/min/mg protein, respectively. The uptake process is inhibited by unlabelled structural analogs (lumiflavin, lumichrome) but not by structurally unrelated vitamins. Ca++/calmodulin and protein kinase A (PKA) pathways are found to play an important role in the intracellular regulation of [3H]-Riboflavin. Apical and baso-lateral uptake of [3H]-Riboflavin clearly indicate that riboflavin specific transport system is predominantly localized on the apical side of RBE4 cells. A 628 bp band corresponding to riboflavin transporter is revealed in RT-PCR analysis. These findings, for the first time report the existence of a specialized and high affinity transport system for riboflavin in RBE4 cells. Blood-brain barrier (BBB) is a major obstacle limiting drug transport inside the brain as it regulates drug permeation from systemic circulation. This transporter can be utilized for targeted delivery in enhancing brain permeation of highly potent drugs on systemic administration. PMID:22683359

  11. Effect of Nasal CPAP on SIRT1 and Endothelial Function in Obstructive Sleep Apnea Syndrome.

    Science.gov (United States)

    Chen, Wei-Ji; Liaw, Shwu-Fang; Lin, Ching-Chi; Chiu, Chung-Hsin; Lin, Mei-Wei; Chang, Feng-Ting

    2015-12-01

    Sirtuin 1 (SIRT1), a histone/protein deacetylase, has been implicated in aging, metabolism, and stress resistance. SIRT1 regulates endothelial nitric oxide (NO) synthase, restores NO availability, and is involved in different aspects of cardiovascular disease. The aim of this study was to evaluate any abnormalities with regard to SIRT1 protein level in the blood, SIRT1 activity, and impaired endothelial function in patients with obstructive sleep apnea syndrome (OSAS). We also investigated whether or not OSAS patients who received nasal continuous positive airway pressure (CPAP) treatment showed improvements in the levels of SIRT1. Thirty-five patients with moderately severe to severe OSAS who requested nasal CPAP treatment and 20 healthy controls were prospectively enrolled. The SIRT1 protein levels in blood and its activity, and the serum levels of nitric oxide derivative (NO x ) were assessed. All subjects participated in sleep studies, which were repeated 3 months after nasal CPAP treatment in the patients with OSAS. In the patients with OSAS, the level of SIRT1 in the blood, its activity, and that of NO x was lower than those of normal subjects before nasal CPAP treatment. After nasal CPAP treatment, the level of SIRT1 in the blood and its activity increased from 0.55 ± 0.32 pg/μg of total protein and 3085.53 ± 1071.57 arbitrary fluorescence units (AFUs)/μg of total protein to 1.13 ± 0.43 pg/μg of total protein and 5344.65 ± 1579.71 AFUs/μg of total protein. The serum levels of NO x in the patients with OSAS increased from 16.36 ± 5.78 to 25.94 ± 5.17 µM. Successful treatment for OSAS with nasal CPAP can restore blood levels of the SIRT1 protein and its activity and serum levels of NO x .

  12. Anacetrapib, but not evacetrapib, impairs endothelial function in CETP-transgenic mice in spite of marked HDL-C increase.

    Science.gov (United States)

    Simic, Branko; Mocharla, Pavani; Crucet, Margot; Osto, Elena; Kratzer, Adelheid; Stivala, Simona; Kühnast, Susan; Speer, Thimoteus; Doycheva, Petia; Princen, Hans M; van der Hoorn, Jose W; Jukema, J Wouter; Giral, Hector; Tailleux, Anne; Landmesser, Ulf; Staels, Bart; Lüscher, Thomas F

    2017-02-01

    High-density lipoprotein cholesterol (HDL-C) is inversely related to cardiovascular risk. HDL-C raising ester transfer protein (CETP) inhibitors, are novel therapeutics. We studied the effects of CETP inhibitors anacetrapib and evacetrapib on triglycerides, cholesterol and lipoproteins, cholesterol efflux, paraoxonase activity (PON-1), reactive oxygen species (ROS), and endothelial function in E3L and E3L.CETP mice. Triglycerides and cholesterol were measured at weeks 5, 14 and 21 in E3L.CETP mice on high cholesterol diet and treated with anacetrapib (3 mg/kg/day), evacetrapib (3 mg/kg/day) or placebo. Cholesterol efflux was assessed ex-vivo in mice treated with CETP inhibitors for 3 weeks on a normal chow diet. Endothelial function was analyzed at week 21 in isolated aortic rings, and serum lipoproteins assessed by fast-performance liquid chromatography. Anacetrapib and evacetrapib increased HDL-C levels (5- and 3.4-fold, resp.) and reduced triglycerides (-39% vs. placebo, p = 0.0174). Total cholesterol levels were reduced only in anacetrapib-treated mice (-32%, p = 0.0386). Cholesterol efflux and PON-1 activity (+45% and +35% vs. control, p < 0.005, resp.) were increased, while aortic ROS production was reduced with evacetrapib (-49% vs. control, p = 0.020). Anacetrapib, but not evacetrapib, impaired endothelium dependent vasorelaxation (p < 0.05). In contrast, no such effects were observed in E3L mice for all parameters tested. Notwithstanding a marked rise in HDL-C, evacetrapib did not improve endothelial function, while anacetrapib impaired it, suggesting that CETP inhibition does not provide vascular protection. Anacetrapib exerts unfavorable endothelial effects beyond CETP inhibition, which may explain the neutral results of large clinical trials in spite of increased HDL-C. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Humanin preserves endothelial function and prevents atherosclerotic plaque progression in hypercholesterolemic ApoE deficient mice.

    Science.gov (United States)

    Oh, Yun K; Bachar, Adi R; Zacharias, David G; Kim, Sung Gyun; Wan, Junxiang; Cobb, Laura J; Lerman, Lilach O; Cohen, Pinchas; Lerman, Amir

    2011-11-01

    Humanin (HN) is a cytoprotective peptide derived from endogenous mitochondria, expressed in the endothelial layer of human vessels, but its role in atherogenesis in vivo is not known. In vitro study, however, HN reduced oxidized low-density lipoprotein induced formation of reactive oxygen species and apoptosis. The present study tested the hypothesis that long term treatment with HN will have a protective role against endothelial dysfunction and progression of atherosclerosis in vivo. Daily intraperitonial injection of the HN analogue HNGF6A for 16 weeks prevented endothelial dysfunction and decreased atherosclerotic plaque size in the proximal aorta of ApoE-deficient mice fed on a high cholesterol diet, without showing direct vasoactive effects or cholesterol-reducing effects. HN was expressed in the endothelial layer on the aortic plaques. HNGF6A treatment reduced apoptosis and nitrotyrosine immunoreactivity in the aortic plaques without affecting the systemic cytokine profile. HNGF6A also preserved expression of endothelial nitric oxide synthase in aorta. HN may have a protective effect on endothelial function and progression of atherosclerosis by modulating oxidative stress and apoptosis in the developing plaque. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  15. Endothelial dysfunction

    OpenAIRE

    Yaylalı, Yalın Tolga; Küçükaslan, Mete

    2011-01-01

    Endothelium is a multi-functional cluster of cells within the vascular system consisting of a single layer ofsquamous epithelium. Physiologically, endothelium performs various arrangement and protection functions.However, when these functions are disturbed toward derangement, endothelium also mediates pathologicalfunctions with negative effects on the body. Endothelial dysfunction is mediated by several mediators (nitricoxide, endothelins, prostaglandins, angiotensin 2, etc). Endothelial dysf...

  16. Characterization of immortalized human dermal microvascular endothelial cells (HMEC-1) for the study of HDL functionality.

    Science.gov (United States)

    Muñoz-Vega, Mónica; Massó, Felipe; Páez, Araceli; Carreón-Torres, Elizabeth; Cabrera-Fuentes, Hector A; Fragoso, José Manuel; Pérez-Hernández, Nonanzit; Martinez, Laurent O; Najib, Souad; Vargas-Alarcón, Gilberto; Pérez-Méndez, Óscar

    2018-03-09

    Primary cultures endothelial cells have been used as models of endothelial related diseases such atherosclerosis. Biological behavior of primary cultures is donor-dependent and data could not be easily reproducible; endothelial cell lines are emerging options, particularly, human dermal microvascular endothelial cells (HMEC-1), that should be validated to substitute primary cultures for the study of HDL functions. Morphology, size and granularity of cells were assessed by phase contrast microscopy and flow cytometry of HMEC-1. The adhesion molecules, ICAM-1and VCAM-1 after TNF-α stimulation, and endothelial markers CD105 endoglin, as well as HDL receptor SR-BI were determined by flow cytometry. Internalization of HDL protein was demonstrated by confocal microscopy using HDL labeled with Alexa Fluor 488. HUVECs were used as reference to compared the characteristics with HMEC-1. HMEC-1 and HUVEC had similar morphologies, size and granularity. HMEC-1 expressed endothelial markers as HUVECs, as well as functional SR-B1 receptor since the cell line was able to internalize HDL particles. HMEC-1 effectively increased ICAM-1 and VCAM-1 expression after TNF-α stimulation. HUVECs showed more sensibility to TNF-α stimulus but the range of ICAM-1 and VCAM-1 expression was less homogeneous than in HMEC-1, probably due to biological variation of the former. Finally, the expression of adhesion molecules in HMEC-1 was attenuated by co-incubation with HDL. HMEC-1 possess characteristics of endothelial cells, similar to HUVECs, being a cell line suitable to evaluate the functionality of HDL vis-à-vis the endothelium.

  17. Long noncoding RNA MALAT1 regulates endothelial cell function and vessel growth.

    Science.gov (United States)

    Michalik, Katharina M; You, Xintian; Manavski, Yosif; Doddaballapur, Anuradha; Zörnig, Martin; Braun, Thomas; John, David; Ponomareva, Yuliya; Chen, Wei; Uchida, Shizuka; Boon, Reinier A; Dimmeler, Stefanie

    2014-04-25

    The human genome harbors a large number of sequences encoding for RNAs that are not translated but control cellular functions by distinct mechanisms. The expression and function of the longer transcripts namely the long noncoding RNAs in the vasculature are largely unknown. Here, we characterized the expression of long noncoding RNAs in human endothelial cells and elucidated the function of the highly expressed metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). Endothelial cells of different origin express relative high levels of the conserved long noncoding RNAs MALAT1, taurine upregulated gene 1 (TUG1), maternally expressed 3 (MEG3), linc00657, and linc00493. MALAT1 was significantly increased by hypoxia and controls a phenotypic switch in endothelial cells. Silencing of MALAT1 by small interfering RNAs or GapmeRs induced a promigratory response and increased basal sprouting and migration, whereas proliferation of endothelial cells was inhibited. When angiogenesis was further stimulated by vascular endothelial growth factor, MALAT1 small interfering RNAs induced discontinuous sprouts indicative of defective proliferation of stalk cells. In vivo studies confirmed that genetic ablation of MALAT1 inhibited proliferation of endothelial cells and reduced neonatal retina vascularization. Pharmacological inhibition of MALAT1 by GapmeRs reduced blood flow recovery and capillary density after hindlimb ischemia. Gene expression profiling followed by confirmatory quantitative reverse transcriptase-polymerase chain reaction demonstrated that silencing of MALAT1 impaired the expression of various cell cycle regulators. Silencing of MALAT1 tips the balance from a proliferative to a migratory endothelial cell phenotype in vitro, and its genetic deletion or pharmacological inhibition reduces vascular growth in vivo.

  18. Sequential changes in canine pulmonary epithelial and endothelial cell functions after nitrogen dioxide

    International Nuclear Information System (INIS)

    Man, S.F.; Williams, D.J.; Amy, R.A.; Man, G.C.; Lien, D.C.

    1990-01-01

    Through its ability to cause lipid peroxidation, nitrogen dioxide (NO 2 ) may affect the functional properties of both the pulmonary epithelium and endothelium. We evaluated this possibility in 13 mongrel dogs by exposing these animals to 200 or 400 ppm NO 2 for 1 h. The changes in pulmonary epithelial permeability (using a radioaerosol technique), FRC, and endothelial function (the removal of radiolabeled serotonin, [ 14 C]5-HT, and prostaglandin E1, [3H]PGE1, from the pulmonary circulation) were measured at 1 h and at 2, 7, or 14 days after NO 2 exposure. In another six dogs, we evaluated changes in cell population and albumin in bronchoalveolar lavage (BAL) fluid caused by NO 2 . In the first two days after NO 2 exposure, focal pulmonary edema was documented on microscopy, radioaerosol clearance was delayed, and FRC decreased slightly. BAL showed a marked increase in albumin, but the removal of trace amounts of 5-HT and PGE1 by the endothelium was not altered. All physiologic abnormalities returned to normal with time

  19. Sequential changes in canine pulmonary epithelial and endothelial cell functions after nitrogen dioxide

    Energy Technology Data Exchange (ETDEWEB)

    Man, S.F.; Williams, D.J.; Amy, R.A.; Man, G.C.; Lien, D.C. (Univ. of Alberta, Edmonton (Canada))

    1990-07-01

    Through its ability to cause lipid peroxidation, nitrogen dioxide (NO{sub 2}) may affect the functional properties of both the pulmonary epithelium and endothelium. We evaluated this possibility in 13 mongrel dogs by exposing these animals to 200 or 400 ppm NO{sub 2} for 1 h. The changes in pulmonary epithelial permeability (using a radioaerosol technique), FRC, and endothelial function (the removal of radiolabeled serotonin, ({sup 14}C)5-HT, and prostaglandin E1, (3H)PGE1, from the pulmonary circulation) were measured at 1 h and at 2, 7, or 14 days after NO{sub 2} exposure. In another six dogs, we evaluated changes in cell population and albumin in bronchoalveolar lavage (BAL) fluid caused by NO{sub 2}. In the first two days after NO{sub 2} exposure, focal pulmonary edema was documented on microscopy, radioaerosol clearance was delayed, and FRC decreased slightly. BAL showed a marked increase in albumin, but the removal of trace amounts of 5-HT and PGE1 by the endothelium was not altered. All physiologic abnormalities returned to normal with time.

  20. Hibiscus sabdariffa extract lowers blood pressure and improves endothelial function.

    Science.gov (United States)

    Joven, Jorge; March, Isabel; Espinel, Eugenia; Fernández-Arroyo, Salvador; Rodríguez-Gallego, Esther; Aragonès, Gerard; Beltrán-Debón, Raúl; Alonso-Villaverde, Carlos; Rios, Lidia; Martin-Paredero, Vicente; Menendez, Javier A; Micol, Vicente; Segura-Carretero, Antonio; Camps, Jordi

    2014-06-01

    Polyphenols from Hibiscus sabdariffa calices were administered to patients with metabolic syndrome (125 mg/kg/day for 4 wk, n = 31) and spontaneously hypertensive rats (125 or 60 mg/kg in a single dose or daily for 1 wk, n = 8 for each experimental group). The H. sabdariffa extract improved metabolism, displayed potent anti-inflammatory and antioxidant activities, and significantly reduced blood pressure in both humans and rats. Diuresis and inhibition of the angiotensin I-converting enzyme were found to be less important mechanisms than those related to the antioxidant, anti-inflammatory, and endothelium-dependent effects to explain the beneficial actions. Notably, polyphenols induced a favorable endothelial response that should be considered in the management of metabolic cardiovascular risks. © 2014 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. 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

    not necessarily follow that insulin resistance and (or) hyperglycemia is causing the inability to respond properly to vasodilatory stimuli. Rather, this could be related to the impact of concomitant cardiovascular risk factors that are almost invariably present in patients with type 2 diabetes. The impact...... 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...

  2. Microcapsules functionalized with neuraminidase can enter vascular endothelial cells in vitro.

    Science.gov (United States)

    Liu, Weizhi; Wang, Xiaocong; Bai, Ke; Lin, Miao; Sukhorukov, Gleb; Wang, Wen

    2014-12-06

    Microcapsules made of polyelectrolyte multilayers exhibit no or low toxicity, appropriate mechanical stability, variable controllable degradation and can incorporate remote release mechanisms triggered by various stimuli, making them well suited for targeted drug delivery to live cells. This study investigates interactions between microcapsules made of synthetic (i.e. polystyrenesulfonate sodium salt/polyallylamine hydrochloride) or natural (i.e. dextran sulfate/poly-L-arginine) polyelectrolyte and human umbilical vein endothelial cells with particular focus on the effect of the glycocalyx layer on the intake of microcapsules by endothelial cells. Neuraminidase cleaves N-acetyl neuraminic acid residues of glycoproteins and targets the sialic acid component of the glycocalyx on the cell membrane. Three-dimensional confocal images reveal that microcapsules, functionalized with neuraminidase, can be internalized by endothelial cells. Capsules without neuraminidase are blocked by the glycocalyx layer. Uptake of the microcapsules is most significant in the first 2 h. Following their internalization by endothelial cells, biodegradable DS/PArg capsules rupture by day 5; however, there is no obvious change in the shape and integrity of PSS/PAH capsules within the period of observation. Results from the study support our hypothesis that the glycocalyx functions as an endothelial barrier to cross-membrane movement of microcapsules. Neuraminidase-loaded microcapsules can enter endothelial cells by localized cleavage of glycocalyx components with minimum disruption of the glycocalyx layer and therefore have high potential to act as drug delivery vehicles to reach tissues beyond the endothelial barrier of blood vessels. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  3. Does exercise and the stress of clinical examination influence endothelial function in dogs with mitral regurgitation?

    DEFF Research Database (Denmark)

    Moesgaard, Sophia Gry; Pedersen, Henrik Duelund; Holte, Andreas

    2005-01-01

    to indicate endothelial function. As in man with heart failure, mitral regurgitation (MR) associated with mitral valve prolapse in dogs, has been found to be associated with a decreased plasma concentation of NOx early in the course of heart failure. Correction of such endothelial dysfunction in human...... subjects is regarded as being an important therapeutic target.An aim of this PhD project is to investigate the involvement of NO in mitral valve disease and explain possible reasons for the decrease in NOx seen in connection with MR.When dogs are examined under clinic conditions there is an inevitable...... amount of stress and agitation, which may affect the cardiovascular system and endothelial function. Plasma NOx measured in dogs with MR in their home environment was similar to that of dogs without MR which were measured in the clinic. However, the same dogs with MR showed a significant decrease...

  4. Assessment of endothelial function during oral contraception in women with insulin-dependent diabetes mellitus

    DEFF Research Database (Denmark)

    Petersen, K R; Skouby, S O; Sidelmann, Johannes Jakobsen

    1994-01-01

    The effects of contraceptive steroids on the expression of endothelial homeostasis were examined by direct and indirect measures in women with insulin-dependent diabetes mellitus (IDDM) in a prospective nonrandomized controlled study. Study subjects were 13 women with uncomplicated IDDM treated...... with a monophasic combination of 30 micrograms ethinyl estradiol and 75 micrograms gestodene for 12 consecutive cycles and 13 women of comparable diabetic status as control. During the study period, none of the participants developed increased renal albumin excretion, which was used as a direct measure...... of endothelial function. In the indirect assessment of endothelial function, we found a proportionate increase in plasma levels of thrombin-antithrombin III (TAT) complexes and D-dimer during treatment. Hormonal intake was followed by decreased antigen concentrations of tissue plasminogen activator (t...

  5. Androgen Modulates Functions of Endothelial Progenitor Cells through Activated Egr1 Signaling

    Directory of Open Access Journals (Sweden)

    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.

  6. Normalized impedance function and the straightforward inversion ...

    Indian Academy of Sciences (India)

    inverted through SIS for comparison. We noticed that the new function and SIS compliment each other and ... The process of inverting the MT data sets, usually of inadequate quality and quantity, is beset by the endemic ..... ter α controls the depth to which a conductive hori- zon can be detected as demonstrated for the Cull.

  7. Normalized impedance function and the straightforward inversion ...

    Indian Academy of Sciences (India)

    The linear straightforward inversion scheme (SIS),developed by the authors employing the concept of equal penetration layers,has been used to validate the proposed apparent resistivity functions.For this purpose,several ... Department of Earth Sciences, Indian Institute of Technology Roorkee, Roorkee, UA 247 667, India.

  8. 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...... function, 24 hour ambulatory blood pressure and heart rate during treatment with carvedilol, metoprolol tartrate and metoprolol succinate in patients with HF....

  9. 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....

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

    DEFF Research Database (Denmark)

    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 subjec...

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

    Science.gov (United States)

    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

  12. Is a low level of free thyroxine in the maternal circulation associated with altered endothelial function in Gestational Diabetes?

    Directory of Open Access Journals (Sweden)

    Enrique eGuzmán-Gutiérrez

    2014-06-01

    Full Text Available Synthesis of thyroid hormones, thyroxine (T4 and tri-iodothyronine (T3, in the human fetus starts from 17-19th weeks of gestation. Despite the majority of normal pregnant women reaching adequate levels of circulating thyroid hormones, in some cases, women with normal pregnancies have low level of free T4 during first trimester of pregnancy, suggesting that T4 action may be compromised in those women and their fetuses. In addition, pathological low levels of thyroid hormones are detected in isolated maternal hypothyroxemia (IMH and clinical hypothyroidism. Nevertheless, human placenta regulates T3/T4 concentration in the fetal circulation by modulating the expression and activity of both thyroid hormone transporters (THT and deiodinases. Then, placenta can control the availability of T3/T4 in the feto-placental circulation, and therefore may generate an adaptive response in cases where the mother courses with low levels of T4. In addition, T3/T4 might control vascular response in the placenta, in particularly endothelial cells may induce the synthesis and release of vasodilators such as nitric oxide (NO or vasoconstrictors such as endothelin-1 mediated by these hormones. On the other hand, low levels of T4 have been associated with increase in gestational diabetes (GD markers. Since GD is associated with impaired placental vascular function characterized by increased NO synthesis in placental arteries and veins, as well as elevated placental angiogenesis, it is unknown whether reduced T4 level at the maternal circulation could result in an altered placental endothelial function during GD. In this review, we analyze available information regarding thyroid hormones and endothelial dysfunction in GD; and propose that low maternal levels of T4 observed in GD may be compensated by increased placental availability of T3/T4 via elevation in the activity of THT and/or reduction in deiodinases in the feto-placental circulation.

  13. Omega-3 fatty acids plus rosuvastatin improves endothelial function in South Asians with dyslipidemia

    Directory of Open Access Journals (Sweden)

    Catalin Mindrescu

    2008-12-01

    Full Text Available Catalin Mindrescu1,2,3, Rakesh P Gupta1,3, Eileen V Hermance1, Mary C DeVoe1, Vikas R Soma1, John T Coppola1,2, Cezar S Staniloae1,21Comprehensive Cardiovascular Center, Saint Vincent’s Hospital Manhattan, New York, NY, USA; 2New York Medical College, Valhalla, NY, USA; 3Rakesh P Gupta and Catalin Mindrescu contributed equally to this article.Background: The present study was undertaken to investigate the effect of statins plus omega-3 polyunsaturated fatty acids (PUFAs on endothelial function and lipid profile in South Asians with dyslipidemia and endothelial dysfunction, a population at high risk for premature coronary artery disease.Methods: Thirty subjects were randomized to rosuvastatin 10 mg and omega-3-PUFAs 4 g or rosuvastatin 10 mg. After 4 weeks, omega-3-PUFAs were removed from the first group and added to subjects in the second group. All subjects underwent baseline, 4-, and 8-week assessment of endothelial function and lipid profile.Results: Compared to baseline, omega-3-PUFAs plus rosuvastatin improved endothelial-dependent vasodilation (EDV: −1.42% to 11.36%, p = 0.001, and endothelial-independent vasodilation (EIV: 3.4% to 17.37%, p = 0.002. These effects were lost when omega-3-PUFAs were removed (EDV: 11.36% to 0.59%, p = 0.003. In the second group, rosuvastatin alone failed to improve both EDV and EIV compared to baseline. However, adding omega-3-PUFAs to rosuvastatin, significantly improved EDV (−0.66% to 14.73%, p = 0.001 and EIV (11.02% to 24.5%, p = 0.001. Addition of omega-3-PUFAs further improved the lipid profile (triglycerides 139 to 91 mg/dl, p = 0.006, low-density lipoprotein cholesterol 116 to 88 mg/dl, p = 0.014.Conclusions: Combined therapy with omega-3-PUFAs and rosuvastatin improves endothelial function in South Asian subjects with dyslipidemia and endothelial dysfunction.Keywords: omega-3 fatty acids, endothelial function, South Asians, dyslipidemia, rosuvastatin

  14. 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...

  15. 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

  16. The exposure-dependent effects of aged secondhand smoke on endothelial function.

    Science.gov (United States)

    Frey, Paul F; Ganz, Peter; Hsue, Priscilla Y; Benowitz, Neal L; Glantz, Stanton A; Balmes, John R; Schick, Suzaynn F

    2012-05-22

    The aim of this study was to investigate whether exposure to a range of relatively low concentrations of aged secondhand smoke (SHS), similar to those encountered commonly in the community, would impair endothelial function in a concentration-dependent manner. Exposure to SHS impairs endothelial function in humans. The concentration-dependent relationship for aged SHS effects on endothelial function after an exposure of short duration is unknown. Thirty-three healthy nonsmokers were exposed to 1 of 2 low levels of aged SHS or to conditioned filtered air for 30 min. The primary end point was change in maximal percent brachial artery flow-mediated dilation after exposure. In a linear regression model for each increase in SHS exposure by 100 μg/m(3) respirable suspended particles, the absolute maximal percent brachial artery flow-mediated dilation was reduced by 0.67%. We did not find evidence of a threshold for the effect of SHS on flow-mediated dilation. Short-term exposure to real-world levels of aged SHS for 30 min resulted in a concentration-dependent decrease in endothelial function as measured by flow-mediated dilation. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  17. [Effects of glucose concentration fluctuation on function of cultured bovine arterial endothelial cells].

    Science.gov (United States)

    Ye, Xi-yun; Tu, Qian; Tong, Zhi; Weng, Yu-jing; Wang, Yao-fa

    2010-03-01

    To explore the effects of glucose concentration fluctuation on function of cultured bovine arterial endothelial cells and underlying mechanism. The thoracic aorta of newborn calf was used for primary endothelial cells culture. Cells were divided into 3 groups and cultured for 48 h: control group (C, 5.5 mmol/L), constant high glucose group (HG, 30 mmol/L) and glucose fluctuation (GF, three circles of 2 h 30 mmol/L followed by 3 h 5.5 mmol/L, 30 mmol/L overnight, repeat the whole procedure on the following day) groups. The membranes fluidity of endothelial cells was detected by fluorescence polarization method. The contents of sorbierite, aldose reductase (AR), sorbitol dehydrogenase (SDH) and advanced glycation end products (AGEs) were measured. RAGE, eNOS and ET-1 mRNA expressions were detected by semi-quantitative RT-PCR. The membranes fluidity of endothelial cells in HG or GF group were significantly decreased compared with the control group (all P RAGE, eNOS and ET-1 were significantly upregulated compared with the control group (all P bovine arterial endothelial cells dysfunction than high glucose via activating polyols metabolic pathways, upregulating the expression of AGEs, eNOS and ET-1. Therefore, glucose concentration fluctuation might play a crucial role on macrovascular complications of diabetes.

  18. Daily egg consumption in hyperlipidemic adults--effects on endothelial function and cardiovascular risk.

    Science.gov (United States)

    Njike, Valentine; Faridi, Zubaida; Dutta, Suparna; Gonzalez-Simon, Anjelica L; Katz, David L

    2010-07-02

    Limiting consumption of eggs, which are high in cholesterol, is generally recommended to reduce risk of cardiovascular disease. However, recent evidence suggests that dietary cholesterol has limited influence on serum cholesterol or cardiac risk. To assess the effects of egg consumption on endothelial function and serum lipids in hyperlipidemic adults. Randomized, placebo-controlled crossover trial of 40 hyperlipidemic adults (24 women, 16 men; average age = 59.9 +/- 9.6 years; weight = 76.3 +/- 21.8 kilograms; total cholesterol = 244 +/- 24 mg/dL). In the acute phase, participants were randomly assigned to one of the two sequences of a single dose of three medium hardboiled eggs and a sausage/cheese breakfast sandwich. In the sustained phase, participants were then randomly assigned to one of the two sequences of two medium hardboiled eggs and 1/2 cup of egg substitute daily for six weeks. Each treatment assignment was separated by a four-week washout period. Outcome measures of interest were endothelial function measured as flow mediated dilatation (FMD) and lipid panel. Single dose egg consumption had no effects on endothelial function as compared to sausage/cheese (0.4 +/- 1.9 vs. 0.4 +/- 2.4%; p = 0.99). Daily consumption of egg substitute for 6 weeks significantly improved endothelial function as compared to egg (1.0 +/- 1.2% vs. -0.1 +/- 1.5%; p cholesterol (-18 +/- 18 vs. -5 +/- 21 mg/dL; p < 0.01) and LDL (-14 +/- 20 vs. -2 +/- 19 mg/dL; p = 0.01). Study results (positive or negative) are expressed in terms of change relative to baseline. Egg consumption was found to be non-detrimental to endothelial function and serum lipids in hyperlipidemic adults, while egg substitute consumption was beneficial.

  19. Daily egg consumption in hyperlipidemic adults - Effects on endothelial function and cardiovascular risk

    Directory of Open Access Journals (Sweden)

    Gonzalez-Simon Anjelica L

    2010-07-01

    Full Text Available Abstract Background Limiting consumption of eggs, which are high in cholesterol, is generally recommended to reduce risk of cardiovascular disease. However, recent evidence suggests that dietary cholesterol has limited influence on serum cholesterol or cardiac risk. Objective To assess the effects of egg consumption on endothelial function and serum lipids in hyperlipidemic adults. Methods Randomized, placebo-controlled crossover trial of 40 hyperlipidemic adults (24 women, 16 men; average age = 59.9 ± 9.6 years; weight = 76.3 ± 21.8 kilograms; total cholesterol = 244 ± 24 mg/dL. In the acute phase, participants were randomly assigned to one of the two sequences of a single dose of three medium hardboiled eggs and a sausage/cheese breakfast sandwich. In the sustained phase, participants were then randomly assigned to one of the two sequences of two medium hardboiled eggs and 1/2 cup of egg substitute daily for six weeks. Each treatment assignment was separated by a four-week washout period. Outcome measures of interest were endothelial function measured as flow mediated dilatation (FMD and lipid panel. Results Single dose egg consumption had no effects on endothelial function as compared to sausage/cheese (0.4 ± 1.9 vs. 0.4 ± 2.4%; p = 0.99. Daily consumption of egg substitute for 6 weeks significantly improved endothelial function as compared to egg (1.0 ± 1.2% vs. -0.1 ± 1.5%; p p p = 0.01. Study results (positive or negative are expressed in terms of change relative to baseline. Conclusions Egg consumption was found to be non-detrimental to endothelial function and serum lipids in hyperlipidemic adults, while egg substitute consumption was beneficial.

  20. Effect of dietary nitrate on blood pressure, endothelial function, and insulin sensitivity in type 2 diabetes.

    Science.gov (United States)

    Gilchrist, Mark; Winyard, Paul G; Aizawa, Kunihiko; Anning, Christine; Shore, Angela; Benjamin, Nigel

    2013-07-01

    Diets rich in green, leafy vegetables have been shown to lower blood pressure (BP) and reduce the risk of cardiovascular disease. Green, leafy vegetables and beetroot are particularly rich in inorganic nitrate. Dietary nitrate supplementation, via sequential reduction to nitrite and NO, has previously been shown to lower BP and improve endothelial function in healthy humans. We sought to determine if supplementing dietary nitrate with beetroot juice, a rich source of nitrate, will lower BP and improve endothelial function and insulin sensitivity in individuals with type 2 diabetes (T2DM). Twenty-seven patients, age 67.2±4.9 years (18 male), were recruited for a double-blind, randomized, placebo-controlled crossover trial. Participants were randomized to begin, in either order, a 2-week period of supplementation with 250ml beetroot juice daily (active) or 250ml nitrate-depleted beetroot juice (placebo). At the conclusion of each intervention period 24-h ambulatory blood pressure monitoring, tests of macro- and microvascular endothelial function, and a hyperinsulinemic isoglycemic clamp were performed. After 2 weeks administration of beetroot juice mean ambulatory systolic BP was unchanged: 134.6±8.4mmHg versus 135.1±7.8mmHg (mean±SD), placebo vs active-mean difference of -0.5mmHg (placebo-active), p=0.737 (95% CI -3.9 to 2.8). There were no changes in macrovascular or microvascular endothelial function or insulin sensitivity. Supplementation of the diet with 7.5mmol of nitrate per day for 2 weeks caused an increase in plasma nitrite and nitrate concentration, but did not lower BP, improve endothelial function, or improve insulin sensitivity in individuals with T2DM. Copyright © 2013 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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.

  2. [The altered endothelial function in patients with arterial hypertension and different forms of atrial fibrillation].

    Science.gov (United States)

    Podzolkov, V I; Tarzimanova, A I; Mokhammadi, L N

    2014-01-01

    The role of endothelial function in the development of cardiovascular diseases has recently attracted attention of many researchers due to increasingly more data suggesting the relationship between endothelial dysfunction (ED) and disturbed cardiac rhythms including atrial fibrillation (AF). ED is known to precede lesions in target organs related to arterial hypertension (AH) which makes the study of endothelial function as an early marker of vascular lesions in AH and AF a topical issue. To study changes of endothelial function in patients with AH and AF. Group 1 included 84 patients with AH (inclusion criteria: essential AH and confirmed paroxysm of AF), group 2 contained 20 patients with AH and permanent AF, control group was comprised of 30 AH patients without AF. The vasomotor function of endothelium was evaluated from reactive hyperemia determined by the ultrasonic method, blood samples for biochemical analysis and determination of Willebrand factor (WF) were taken during fasting. Patients of group 2 showed significant changes of endothelium-dependent vasodilation of the brachial artery. Its diameter within 60 sec after decompression increased by 5.8 +/- 0.9% and 12.3 +/- 1.2% in groups 1 and 3 respectively (p < 0.05). In group 2, collagen-binding activity of WF increased significantly to 1500 +/-140 U/100 ml compared with 1060 +/- 120 and 840 +/- 110 in groups 2 and 3 (p < 0.05). Patients with AH and persistent AF had altered endothelial function in the form of significant decrease of endothelium-dependent vasodilation of the brachial artery and increase of collagen-binding activity of WF.

  3. Effects of cigarette smoke on endothelial function of pulmonary arteries in the guinea pig

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    Martínez Anna

    2009-08-01

    Full Text Available Abstract Background Cigarette smoking may contribute to pulmonary hypertension in chronic obstructive pulmonary disease by altering the structure and function of pulmonary vessels at early disease stages. The objectives of this study were to evaluate the effects of long-term exposure to cigarette smoke on endothelial function and smooth muscle-cell proliferation in pulmonary arteries of guinea pigs. Methods 19 male Hartley guinea pigs were exposed to the smoke of 7 cigarettes/day, 5 days/week, for 3 and 6 months. 17 control guinea pigs were sham-exposed for the same periods. Endothelial function was evaluated in rings of pulmonary artery and aorta as the relaxation induced by ADP. The proliferation of smooth muscle cells and their phenotype in small pulmonary vessels were evaluated by immunohistochemical expression of α-actin and desmin. Vessel wall thickness, arteriolar muscularization and emphysema were assessed morphometrically. The expression of endothelial nitric oxide synthase (eNOS was evaluated by Real Time-PCR. Results Exposure to cigarette smoke reduced endothelium-dependent vasodilatation in pulmonary arteries (ANOVA p Conclusion In the guinea pig, exposure to cigarette smoke induces selective endothelial dysfunction in pulmonary arteries, smooth muscle cell proliferation in small pulmonary vessels and reduced lung expression of eNOS. These changes appear after 3 months of exposure and precede the development of pulmonary emphysema.

  4. 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.

  5. 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.

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

    Science.gov (United States)

    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.

  7. 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.

  8. Oxidative Stress in Hypertensive Patients Induces an Increased Contractility in Vein Grafts Independent of Endothelial Function

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    Claudio Joo Turoni

    2011-01-01

    Full Text Available Objective. To evaluate the impact of oxidative stress on vascular reactivity to vasoconstrictors and on nitric oxide (NO bioavailability in saphenous vein (SV graft with endothelial dysfunction from hypertensive patients (HT. Methods. Endothelial function, vascular reactivity, oxidative state, nitrites and NO release were studied in isolated SV rings from HT and normotensive patients (NT. Only rings with endothelial dysfunction were used. Results. HT rings presented a hyperreactivity to vasoconstrictors that was reverted by diphenylene iodonium (DPI. In NT, no effect of DPI was obtained, but Nω-nitro-L-arginine methyl ester (L-NAME increased the contractile response. NO was present in SV rings without endothelial function. Nitrites were higher in NT than in HT (1066.1 ± 86.3 pmol/mg; n=11 versus 487.8 ± 51.6; n=23; P<0.01 and inhibited by nNOS inhibitor. L-arginine reversed this effect. Antioxidant agents increased nitrites and NO contents only in HT. The anti-nNOS-stained area by immunohistochemistry was higher in NT than HT. HT showed an elevation of oxidative state. Conclusions. Extraendothelial NO counter-regulates contractility in SV. However, this action could be altered in hypertensive situations by an increased oxidative stress or a decreased ability of nNOS to produce NO. Further studies should be performed to evaluate the implication of these results in graft patency rates.

  9. Src Family Kinases Modulate the Loss of Endothelial Barrier Function in Response to TNF-α: Crosstalk with p38 Signaling.

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    Alejandro P Adam

    Full Text Available Activation of Src Family Kinase (SFK signaling is required for the increase in endothelial permeability induced by a variety of cytokines and growth factors. However, we previously demonstrated that activation of endogenous SFKs by expression of dominant negative C-terminal Src Kinase (DN-Csk is not sufficient to decrease endothelial adherens junction integrity. Basal SFK activity has been observed in normal venular endothelia and was not associated with increased basal permeability. The basal SFK activity however was found to contribute to increased sensitivity of the venular endothelium to inflammatory mediator-induced leakage. How SFK activation achieves this is still not well understood. Here, we show that SFK activation renders human dermal microvascular endothelial cells susceptible to low doses of TNF-α. Treatment of DN-Csk-expressing cells with 50 pg/ml TNF-α induced a loss of TEER as well as drastic changes in the actin cytoskeleton and focal adhesion proteins. This synergistic effect was independent of ROCK or NF-κB activity. TNF-α-induced p38 signaling was required for the synergistic effect on barrier function, and activation of the p38 MAPK alone was also able to induce changes in permeability only in monolayers with active SFKs. These results suggest that the activation of endogenous levels of SFK renders the endothelial barrier more susceptible to low, physiologic doses of TNF-α through activation of p38 which leads to a loss of endothelial tight junctions.

  10. The effects of Ramadan fasting on endothelial function in patients with cardiovascular diseases.

    Science.gov (United States)

    Yousefi, B; Faghfoori, Z; Samadi, N; Karami, H; Ahmadi, Y; Badalzadeh, R; Shafiei-Irannejad, V; Majidinia, M; Ghavimi, H; Jabbarpour, M

    2014-07-01

    Endothelial dysfunction, which can be manifested by loss of nitric oxide bioavailability, is an increasingly recognized cause of cardiovascular diseases. Previous studies showed that diets affect endothelial function and modify cardiovascular risks. This study aimed to assess the effects of Ramadan fasting, as a diet intervention, on endothelial function. The study population consisted of 21 male patients (mean age: 52±9 years) with cardiovascular risks (coronary artery disease, cerebrovascular or peripheral arterial diseases). The biochemical variables in serum of patients were measured 2 days before and after Ramadan fasting. The levels of asymmetric dimethylarginine (ADMA) and vascular endothelial growth factor (VEGF) were evaluated using the enzyme-linked immunosorbent assay. Nitric oxide (NO) and Malondialdehyde (MDA) levels were measured by the Griess and thiobarbituric acid reaction substances assay, respectively. NO levels in patients after Ramadan fasting were significantly higher compared with the baseline value (85.1±11.54 vs 75.8±10.7 μmol/l) (PRamadan levels of ADMA decreased significantly in comparison with pre-Ramadan levels (802.6±60.9 vs 837.6±51.0 nmol/l) (PRamadan fasting, but these changes were not statistically significant (228.1±27.1 vs 222.7±22.9 pg/ml and 3.2±0.7 vs 3.6±1.1 μmol/l, respectively). Ramadan fasting may have beneficial effects on endothelial function and can modulate cardiovascular risks. Further studies are needed to confirm the clinical significance of Ramadan fasting on cardiovascular health.

  11. Assessment of endothelial function by flow-mediated dilation in diabetic patients: Effects of physical exercise

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    Aline P Jarrete

    2016-03-01

    Full Text Available Abstract The endothelium is now recognized as an endocrine organ that acts to maintain vascular homeostasis regulating the vascular tone and structure. The endothelial cells synthetize a variety of mediators among them, the main agent is the nitric oxide (NO, a potent vasodilator. NO exerts its protective role preventing leukocyte adhesion and migration, expression of adhesion molecules, platelet aggregation, cell proliferation, and promoting the relaxation of smooth muscle cells. On the other hand, endothelial dysfunction present in many chronic diseases such as atherosclerosis, coronary artery disease, peripheral artery disease, hypertension and diabetes mellitus, is characterized by reduced NO bioavailability. Thus, a few decades ago, measurement of endothelial function has emerged as valuable tool that provides insights in the pathophysiological mechanisms, opportunity to identify early disease and cardiovascular risk, preventing future events or avoiding the progression of the disease. Diabetic patients, particularly, have been a target to apply this technique, mainly because this condition has been related with an impairment of endothelium-dependent dilation and it is believed that the endothelium dysfunction is the basis of diabetes complications such as coronary artery disease and accelerated atherosclerosis. In addition, cardiovascular complications represent the leading cause of morbidity and death in diabetes mellitus. Besides pharmacological therapy, lifestyle modifications have been recommended by specific organizations as a strategy to improve the endothelial function or even prevent the development of diabetes. The aim of this mini eview is to give an update about the importance of endothelium, most common non-invasive technique to evaluate its function, and to summarize some mechanisms involved in endothelial dysfunction and the beneficial effects of exercise in diabetes mellitus.

  12. 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.

  13. Altered hemodynamics, endothelial function, and protein expression occur with aortic coarctation and persist after repair

    Science.gov (United States)

    Menon, Arjun; Eddinger, Thomas J.; Wang, Hongfeng; Wendell, David C.; Toth, Jeffrey M.

    2012-01-01

    Coarctation of the aorta (CoA) is associated with substantial morbidity despite treatment. Mechanically induced structural and functional vascular changes are implicated; however, their relationship with smooth muscle (SM) phenotypic expression is not fully understood. Using a clinically representative rabbit model of CoA and correction, we quantified mechanical alterations from a 20-mmHg blood pressure (BP) gradient in the thoracic aorta and related the expression of key SM contractile and focal adhesion proteins with remodeling, relaxation, and stiffness. Systolic and mean BP were elevated for CoA rabbits compared with controls leading to remodeling, stiffening, an altered force response, and endothelial dysfunction both proximally and distally. The proximal changes persisted for corrected rabbits despite >12 wk of normal BP (∼4 human years). Computational fluid dynamic simulations revealed reduced wall shear stress (WSS) proximally in CoA compared with control and corrected rabbits. Distally, WSS was markedly increased in CoA rabbits due to a stenotic velocity jet, which has persistent effects as WSS was significantly reduced in corrected rabbits. Immunohistochemistry revealed significantly increased nonmuscle myosin and reduced SM myosin heavy chain expression in the proximal arteries of CoA and corrected rabbits but no differences in SM α-actin, talin, or fibronectin. These findings indicate that CoA can cause alterations in the SM phenotype contributing to structural and functional changes in the proximal arteries that accompany the mechanical stimuli of elevated BP and altered WSS. Importantly, these changes are not reversed upon BP correction and may serve as markers of disease severity, which explains the persistent morbidity observed in CoA patients. PMID:23023871

  14. 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

  15. 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

    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....

  16. 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

  17. 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

  18. Endothelial function in hypertensive obese patients: 1 year after surgically induced weight loss.

    Science.gov (United States)

    Flores, L; Núñez, I; Vidal, J; Rueda, S; Viaplana, J; Rodríguez, L; Esmatjes, E

    2014-09-01

    The aim of this study was to describe the effect of surgically induced weight loss on vascular function measured by flow-mediated dilatation (FMD) in hypertensive obese patients. This prospective study included 33 patients (78 % females, mean age 53 (9) years) undergoing bariatric surgery (BS). Before and 12 months postoperatively, the BMI, 24-h ambulatory BP, high-sensitivity C-reactive protein (hs-CRP), leptin, homeostasis model assessment (HOMA IR), and abdominal fat were measured. Endothelial function was assessed by FMD. After BS, the excess body weight loss was 71 %; the 24-h [systolic 18(11)//diastolic 7(7) mmHg] BP values, hs-CRP, leptin, HOMA, and abdominal fat significantly decreased, with no changes in endothelial function. Weight loss achieved by BS was associated with a significant improvement in BP and metabolic and inflammation parameters, but FMD did not improve.

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

    Science.gov (United States)

    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.

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

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    Y. Liang

    2015-06-01

    Full Text Available 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+ 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+ 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.

  1. 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.

  2. Different vitamin D receptor agonists exhibit differential effects on endothelial function and aortic gene expression in 5/6 nephrectomized rats.

    Science.gov (United States)

    Wu-Wong, J Ruth; Li, Xinmin; Chen, Yung-Wu

    2015-04-01

    Endothelial dysfunction, common in chronic kidney disease (CKD), significantly increases cardiovascular disease risk in CKD patients. This study investigates whether different vitamin D receptor agonists exhibit different effects on endothelial function and on aortic gene expression in an animal CKD model. The 5/6 nephrectomized (NX) rat was treated with or without alfacalcidol (0.02, 0.04 and 0.08μg/kg), paricalcitol (0.04 and 0.08μg/kg), or VS-105 (0.004, 0.01 and 0.16μg/kg). All three compounds at the test doses suppressed serum parathyroid hormone effectively. Alfacalcidol at 0.08μg/kg raised serum calcium significantly. Endothelial function was assessed by pre-contracting thoracic aortic rings with phenylephrine, followed by treatment with acetylcholine or sodium nitroprusside. Uremia significantly affected endothelial-dependent aortic relaxation, which was improved by all three compounds in a dose-dependent manner with alfacalcidol and paricalcitol exhibiting a lesser effect. DNA microarray analysis of aorta samples revealed that uremia impacted the expression of numerous aortic genes, many of which were normalized by the vitamin D analogs. Real-time RT-PCR analysis confirmed that selected genes such as Abra, Apoa4, Fabp2, Hsd17b2, and Hspa1b affected by uremia were normalized by the vitamin D analogs with alfacalcidol exhibiting less of an effect. These results demonstrate that different vitamin D analogs exhibit different effects on endothelial function and aortic gene expression in 5/6 NX rats. This article is part of a Special Issue entitled '17th Vitamin D Workshop'. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. 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 stress. Compared to controls, NASH and FLD patients had higher Nox2 activity and isoprostanes levels and lower FMD and NOx, with a significant gradient between FLD and NASH. The interventional study showed that, compared to baseline, FMD and NOx increased (from 2.9 ± 2.4 to 7.2 ± 3.0% p 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

  4. 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

  5. Regulation of endothelial barrier function during flow-induced conversion to an arterial phenotype.

    Science.gov (United States)

    Seebach, Jochen; Donnert, Gerald; Kronstein, Romy; Werth, Sebastian; Wojciak-Stothard, Beata; Falzarano, Darryl; Mrowietz, Christof; Hell, Stefan W; Schnittler, Hans-J

    2007-08-01

    Flow-induced conversion of endothelial cells into an elongated arterial phenotype requires a coordinated regulation of cell junctions. Here we investigated the effect of acute and chronic flow on junction regulation. Using an extended experimental setup that allows analyses of endothelial barrier function under flow conditions, we found a flow-induced upregulation of the transendothelial electrical resistance within minutes. This was accompanied by an increase in actin filaments along the junctions and vascular endothelial (VE)-cadherin clustering, which was identified at nanoscale resolution by stimulated emission depletion microscopy. In addition, a transient tyrosine phosphorylation of VE-cadherin and catenins occurred within minutes following the onset of flow. VE-cadherin and actin distribution were maintained under chronic flow over 24 h and associated with the upregulation of VE-cadherin and alpha-catenin expression, thus compensating for the cell elongation-mediated increase in cell border length. Importantly, all observed effects were rac1 dependent as verified by the inhibitory effect of dominant negative N17rac1. These results show that flow-induced conversion of endothelial cells into an arterial phenotype occurs while intercellular junctions remain intact. The data place rac1 in a central multimodal regulatory position that might be important in the development of vascular diseases, such as arteriosclerosis.

  6. Inhibition of endothelial cell functions by novel potential cancer chemopreventive agents

    International Nuclear Information System (INIS)

    Bertl, Elisabeth; Becker, Hans; Eicher, Theophil; Herhaus, Christian; Kapadia, Govind; Bartsch, Helmut; Gerhaeuser, Clarissa

    2004-01-01

    Endothelial cells (EC) play a major role in tumor-induced neovascularization and bridge the gap between a microtumor and growth factors such as nutrients and oxygen supply required for expansion. Immortalized human microvascular endothelial cells (HMEC-1) were utilized to assess anti-endothelial effects of 10 novel potential cancer chemopreventive compounds from various sources that we have investigated previously in a human in vitro anti-angiogenic assay. These include the monoacylphloroglucinol isoaspidinol B, 1,2,5,7-tetrahydroxy-anthraquinone, peracetylated carnosic acid (PCA), isoxanthohumol, 2,2',4'-trimethoxychalcone, 3'-bromo-2,4-dimethoxychalcone as well as four synthetic derivatives of lunularic acid, a bibenzyl found in mosses [Int. J. Cancer Prev. 1 (2004) 47]. EC proliferation was inhibited with half-maximal inhibitory concentrations from 0.3 to 49.6 μM, whereas EC migration was affected by most compounds at sub-micromolar concentrations. PCA and the bibenzyl derivative EC 1004 potently prevented differentiation of HMEC-1 into tubule-like structures. Overall, our data indicate that inhibition of endothelial cell function contributes to various extents to the chemopreventive or anti-angiogenic potential of these lead compounds

  7. Monomeric adiponectin increases cell viability in porcine aortic endothelial cells cultured in normal and high glucose conditions: Data on kinases activation

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    Elena Grossini

    2016-09-01

    Full Text Available We found that monomeric adiponectin was able to increase cell viability in porcine aortic endothelial cells (PAE cultured both in normal and high glucose condition. Moreover, in normal glucose condition monomeric adiponectin increased p38MAPK, Akt, ERK1/2 and eNOS phosphorylation in a dose- and time-dependent way. Also in high glucose condition monomeric adiponectin increased eNOS and above kinases phosphorylation with similar patterns but at lower extent. For interpretation of the data presented in this article, please see the research article “Monomeric adiponectin modulates nitric oxide release and calcium movements in porcine aortic endothelial cells in normal/high glucose conditions” (Grossini et al., in press [1].

  8. 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.

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

    Science.gov (United States)

    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.

  10. Retrograde flow and shear rate acutely impair endothelial function in humans.

    Science.gov (United States)

    Thijssen, Dick H J; Dawson, Ellen A; Tinken, Toni M; Cable, N Timothy; Green, Daniel J

    2009-06-01

    Changes in arterial shear stress induce functional and structural vasculature adaptations. Recent studies indicate that substantial retrograde flow and shear can occur through human conduit arteries. In animals, retrograde shear is associated with atherogenic effects. The aim of this study was to examine the impact of incremental levels of retrograde shear on endothelial function in vivo. On 3 separate days, we examined bilateral brachial artery flow-mediated dilation, an index of NO-mediated endothelial function, in healthy men (24+/-3 years) before and after a 30-minute intervention consisting of cuff inflation to 25, 50, or 75 mm Hg. Cuff inflations resulted in "dose"-dependent increases in retrograde shear rate, compared with the noncuffed arm, within subjects (P<0.001). Flow-mediated dilation in the cuffed arm did not change in response to the 25-mm Hg stimulus but decreased significantly after both the 50- and 75-mm Hg interventions (P<0.05). The decrease in flow-mediated dilation after the 75-mm Hg intervention was significantly larger than that observed after a 50-mm Hg intervention (P=0.03). In the noncuffed arm, no changes in shear rate or flow-mediated dilation were observed. These results demonstrate that an increase in retrograde shear rate induces a dose-dependent attenuation of endothelial function in humans. This finding contributes to our understanding regarding the possible detrimental effects of retrograde shear rate in vivo.

  11. Dose-dependent effects of decaffeinated coffee on endothelial function in healthy subjects.

    Science.gov (United States)

    Buscemi, S; Verga, S; Batsis, J A; Tranchina, M R; Belmonte, S; Mattina, A; Re, A; Rizzo, R; Cerasola, G

    2009-10-01

    Coffee is known to contain antioxidant substances whose effects may be blunted because of caffeine that may unfavorably affect the cardiovascular system. This study was designed to investigate the acute dose-dependent effects of decaffeinated coffee (DC) on endothelial function measured by the brachial artery flow-mediated dilation (FMD). A total of 15 (8 men and 7 women) healthy nonobese subjects underwent a single-blind, crossover study. Subjects ingested one and two cups of decaffeinated Italian espresso coffee in random order at 5- to 7-day intervals. In the hour following the ingestion of two cups of DC, FMD increased (mean+/-s.e.m.): 0 min, 7.4+/-0.7%; 30 min, 8.0+/-0.6%; 60 min, 10.8+/-0.8%; Pcoffee on endothelial function. Further studies are needed to investigate the effects of chronic use of DC especially with respect to caffeinated coffee and in subjects with cardiovascular diseases.

  12. Efficacy of functional foods mixture in improving hypercholesterolemia, inflammatory and endothelial dysfunction biomarkers-induced by high cholesterol diet.

    Science.gov (United States)

    Al-Muzafar, Hessah Mohammed; Amin, Kamal Adel

    2017-10-06

    Hypercholesterolemia associated with cardiovascular diseases is a global health issue that could be alleviated by functional foods. This study aimed to explore the effects of a high-cholesterol diet on lipid profile, cardiac, inflammatory, and endothelial dysfunction biomarkers, and the possible improvement by functional foods mixture. Male albino rats weighing 100-150 g were randomly divided into four equal groups: 1st control, giving a normal diet; the 2nd received high-cholesterol diet for 8 weeks, the 3rd received the high-cholesterol diet + functional foods mixture, and the 4th administered high-cholesterol diet +atorvastatin (20 mg) orally. The results showed a significant increase in lipid profile and cardiac biomarkers levels (lactate dehydrogenase, creatine kinase and homocystein), also inflammatory markers, as, tumor necrotic factor alpha and chronic reactive proteins were elevated, moreover, vascular adhesion molecule-1 and nitric oxide synthase were disturbed in high-cholesterol diet compared with normal group. While administration of atorvastatin and functional foods mixture ameliorated these alterations. Administration of functional foods mixture and atorvastatin were effective in treating hypercholesterolemia, reduce the risk of inflammation and cardiovascular biomarkers with a high safety margin. These efficiencies may be due to its active ingredient that improve the imbalance in the measured biomarkers.

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

    Energy Technology Data Exchange (ETDEWEB)

    Lebech, Anne-Mette [Copenhagen University Hospital, Department of Infectious Diseases, Hvidovre (Denmark); Hvidovre University Hospital, Department of Infectious Diseases, Hvidovre (Denmark); Kristoffersen, Ulrik Sloth; Kjaer, Andreas [Rigshospitalet University Hospital, Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen (Denmark); University of Copenhagen, Cluster for Molecular Imaging, Copenhagen (Denmark); Wiinberg, Niels; Petersen, Claus Leth [Frederiksberg University Hospital, Department of Clinical Physiology and Nuclear Medicine, Frederiksberg (Denmark); Kofoed, Kristian; Andersen, Ove [Copenhagen University Hospital, Department of Infectious Diseases, Hvidovre (Denmark); Copenhagen University Hospital, Clinical Research Unit, Hvidovre (Denmark); Hesse, Birger [Rigshospitalet University Hospital, Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen (Denmark); Gerstoft, Jan [Rigshospitalet University Hospital, Department of Infectious Diseases, Copenhagen (Denmark)

    2008-11-15

    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 cholesterol levels. Flow mediated dilation (FMD) of the brachial artery and circulating endothelial markers were also assessed. HIV patients in ART with total cholesterol {<=} 5.5 mmol/L (215 mg/dL; n = 13) or total cholesterol {>=} 6.5 mmol/L (254 mg/dL; n = 12) and healthy controls (n = 14) were included. {sup 13}NH{sub 3} perfusion PET, FMD, and measurement of plasma levels of E-Selectin, ICAM-1, VCAM-1, tPAI-1, and hs-CRP were performed. Baseline myocardial perfusion and the coronary flow reserve measured by PET (3.2 {+-} 0.3, 3.2 {+-} 0.3 and 3.0 {+-} 0.3; ns) was similar in HIV patients with normal or high total cholesterol and controls. FMD did not differ between the groups and was 4.6 {+-} 1.1%, 5.1 {+-} 1.2%, and 4.6 {+-} 0.8%, respectively. Increased levels of plasma E-Selectin, ICAM-1, tPAI-1, and hs-CRP were found in HIV patients when compared to controls (p < 0.05). E-Selectin and ICAM-1 levels were higher in HIV patients receiving protease inhibitors (PI) compared to those not receiving PI (p < 0.05). None of the measured endothelial biomarkers differed between the normal and high cholesterol HIV groups. In ART-treated HIV patients with a low overall cardiovascular risk, no sign of endothelial dysfunction was found not even in hypercholesterolemic patients. Also, the increased level of plasma endothelial markers found in HIV patients was not related to hypercholesterolemia. (orig.)

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

    Science.gov (United States)

    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

  15. Zoledronate inhibits ischemia-induced neovascularization by impairing the mobilization and function of endothelial progenitor cells.

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    Shih-Hung Tsai

    Full Text Available BACKGROUND: Bisphosphonates are a class of pharmacologic compounds that are commonly used to treat postmenopausal osteoporosis and malignant osteolytic processes. Studies have shown that bone marrow-derived endothelial progenitor cells (EPCs play a significant role in postnatal neovascularization. Whether the nitrogen-containing bisphosphonate zoledronate inhibits ischemia-induced neovascularization by modulating EPC functions remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: Unilateral hindlimb ischemia was surgically induced in wild-type mice after 2 weeks of treatment with vehicle or zoledronate (low-dose: 30 μg/kg; high-dose: 100 μg/kg. Doppler perfusion imaging demonstrated that the ischemic limb/normal side blood perfusion ratio was significantly lower in wild-type mice treated with low-dose zoledronate and in mice treated with high-dose zoledronate than in controls 4 weeks after ischemic surgery (control vs. low-dose vs. high-dose: 87±7% vs. *61±18% vs. **49±17%, *p<0.01, **p<0.005 compared to control. Capillary densities were also significantly lower in mice treated with low-dose zoledronate and in mice treated with high-dose zoledronate than in control mice. Flow cytometry analysis showed impaired mobilization of EPC-like cells (Sca-1(+/Flk-1(+ after surgical induction of ischemia in mice treated with zoledronate but normal levels of mobilization in mice treated with vehicle. In addition, ischemic tissue from mice that received zoledronate treatment exhibited significantly lower levels of the active form of MMP-9, lower levels of VEGF, and lower levels of phosphorylated eNOS and phosphorylated Akt than ischemic tissue from mice that received vehicle. Results of the in vitro studies showed that incubation with zoledronate inhibited the viability, migration, and tube-forming capacities of EPC. CONCLUSIONS/SIGNIFICANCE: Zoledronate inhibited ischemia-induced neovascularization by impairing EPC mobilization and angiogenic functions

  16. Endothelial Function Predicts New Hospitalization due to Heart Failure Following Cardiac Resynchronization Therapy.

    Science.gov (United States)

    Yufu, Kunio; Shinohara, Tetsuji; Ebata, Yuki; Ayabe, Reika; Fukui, Akira; Okada, Norihiro; Nakagawa, Mikiko; Takahashi, Naohiko

    2015-11-01

    Cardiac resynchronization therapy (CRT) has been established as a treatment for patients with chronic heart failure (HF). We tested the hypothesis that assessment of peripheral endothelial function is associated with the long-term outcome of CRT and its linkage to coronary flow reserve (CFR) was also investigated. From 2010, a total of 34 consecutive patients implanted with CRT for the treatment of advanced HF were evaluated at baseline (immediately before CRT) and 6-8 months after CRT. Endothelial function was evaluated by measurement of reactive hyperemia peripheral arterial tonometry (RH-PAT). In 24 of 34 patients, CFR was determined by transthoracic echocardiography. Based on the receiver-operating characteristic curves, depressed RH-PAT index (RHI) was defined as ≤1.5. Accurate follow-up information during the mean of 343 ± 120 days was obtained in 20 preserved RHI group (mean age 66 ± 1.8 years) and 14 depressed RHI group (71 ± 2.2 years). Kaplan-Meier survival analysis demonstrated that depressed RHI group had higher prevalence of new hospitalization due to HF progression (log-rank 5.40). Cox proportional hazards regression analysis revealed that the baseline log brain natriuretic peptide (hazard ratio 5.95) and the baseline RHI value (hazard ratio 0.066) were independently associated with the incidence of new hospitalization due to HF progression. The baseline RHI values were positively correlated with the 6-8 months change of CFR (R = 0.434, P = 0.0343). Our results suggest that the baseline peripheral endothelial function could predict the long-term outcome of CRT. The results also suggest that improvement of coronary microcirculation might be associated with the better baseline endothelial function. © 2015 Wiley Periodicals, Inc.

  17. 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.

  18. MicroRNA-21 exhibits antiangiogenic function by targeting RhoB expression in endothelial cells.

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    Céline Sabatel

    Full Text Available BACKGROUND: MicroRNAs (miRNAs are endogenously expressed small non-coding RNAs that regulate gene expression at post-transcriptional level. The recent discovery of the involvement of these RNAs in the control of angiogenesis renders them very attractive in the development of new approaches for restoring the angiogenic balance. Whereas miRNA-21 has been demonstrated to be highly expressed in endothelial cells, the potential function of this miRNA in angiogenesis has never been investigated. METHODOLOGY/PRINCIPAL FINDINGS: We first observed in endothelial cells a negative regulation of miR-21 expression by serum and bFGF, two pro-angiogenic factors. Then using in vitro angiogenic assays, we observed that miR-21 acts as a negative modulator of angiogenesis. miR-21 overexpression reduced endothelial cell proliferation, migration and the ability of these cells to form tubes whereas miR-21 inhibition using a LNA-anti-miR led to opposite effects. Expression of miR-21 in endothelial cells also led to a reduction in the organization of actin into stress fibers, which may explain the decrease in cell migration. Further mechanistic studies showed that miR-21 targets RhoB, as revealed by a decrease in RhoB expression and activity in miR-21 overexpressing cells. RhoB silencing impairs endothelial cell migration and tubulogenesis, thus providing a possible mechanism for miR-21 to inhibit angiogenesis. Finally, the therapeutic potential of miR-21 as an angiogenesis inhibitor was demonstrated in vivo in a mouse model of choroidal neovascularization. CONCLUSIONS/SIGNIFICANCE: Our results identify miR-21 as a new angiogenesis inhibitor and suggest that inhibition of cell migration and tubulogenesis is mediated through repression of RhoB.

  19. A Cell Culture Approach to Optimized Human Corneal Endothelial Cell Function

    Science.gov (United States)

    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

  20. Acute effects of different types of aerobic exercise on endothelial function and arterial stiffness.

    Science.gov (United States)

    Siasos, Gerasimos; Athanasiou, Dimitrios; Terzis, Gerasimos; Stasinaki, Aggeliki; Oikonomou, Evangelos; Tsitkanou, Stavroula; Kolokytha, Theodora; Spengos, Konstantinos; Papavassiliou, Athanasios G; Tousoulis, Dimitris

    2016-09-01

    Chronic aerobic exercise training is associated with improved endothelial function and arterial stiffness and favourable long-term cardiovascular effects. We investigated the acute effects of continuous moderate intensity aerobic exercise (CAE) and high intensity interval aerobic exercise (hIAE) on endothelial function and arterial stiffness in healthy participants. Twenty healthy men were recruited to this cross-over study. They participated in two exercise sessions: (a) CAE, volume at 50% of maximum aerobic work for 30 minutes; and (b) hIAE, interval maximum aerobic work for 30 minutes. Endothelial function was evaluated by flow-mediated dilation in the brachial artery. The carotid femoral pulse wave velocity and the femoral dorsalis pedis pulse wave velocity were measured as indices of central aortic and peripheral arterial stiffness. Measurements were carried out before and immediately after each exercise session. There was no statistically significant difference in the baseline measurements before CAE and hIAE with respect to flow-mediated dilation, the carotid femoral pulse wave velocity and the femoral dorsalis pedis pulse wave velocity (p = NS). Both CAE and hIAE significantly improved the flow-mediated dilation compared with baseline (p exercise. These types of aerobic exercise have a different impact on the central and peripheral arterial stiffness. © The European Society of Cardiology 2016.

  1. Effect of fruit and vegetable concentrates on endothelial function in metabolic syndrome: A randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Ma Yingying

    2011-06-01

    Full Text Available Abstract Background and Objective Dehydrated fruit and vegetable concentrates provide an accessible form of phytonutrient supplementation that may offer cardioprotective effects. This study assessed the effects of two blends of encapsulated juice powder concentrates (with and without added berry powders on endothelial function in persons with metabolic syndrome, a risk factor for type 2 diabetes and cardiovascular disease. Methods Randomized, double blind, placebo controlled crossover clinical trial with three treatment arms. 64 adults with metabolic syndrome were enrolled and received 8-week sequences of each blend of the concentrates and placebo. The primary outcome measure was change in endothelial function (assessed as flow-mediated dilatation of the brachial artery 2 hr after consuming a 75 g glucose load, after 8-weeks of daily consumption (sustained or 2 hr after consumption of a single dose (acute. Secondary outcome measures included plasma glucose, serum insulin, serum lipids, and body weight. Results No significant between-group differences in endothelial function with daily treatment for 8 weeks were seen. No other significant treatment effects were discerned in glucose, insulin, lipids, and weight. Conclusion Encapsulated fruit and vegetable juice powder concentrates did not alter insulin or glucose measures in this sample of adults with metabolic syndrome. Trial Registration clinicaltrials.gov NCT01224743

  2. Bradykinin or acetylcholine as vasodilators to test endothelial venous function in healthy subjects

    Directory of Open Access Journals (Sweden)

    Eneida R. Rabelo

    2008-01-01

    Full Text Available INTRODUCTION: The evaluation of endothelial function has been performed in the arterial bed, but recently evaluation within the venous system has also been explored. Endothelial function studies employ different drugs that act as endothelium-dependent vasodilatory response inductors. OBJECTIVES: The aim of this study is to compare the endothelium-dependent venous vasodilator response mediated by either acetylcholine or bradykinin in healthy volunteers. METHODS AND RESULTS: Changes in vein diameter after phenylephrine-induced venoconstriction were measured to compare venodilation induced by acetylcholine or bradykinin (linear variable differential transformer dorsal hand vein technique. We studied 23 healthy volunteers; 31% were male, and the subject had a mean age of 33 ± 8 years and a mean body mass index of 23 ± 2 kg/m². The maximum endothelium-dependent venodilation was similar for both drugs (p = 0.13, as well as the mean responses for each dose of both drugs (r = 0.96. The maximum responses to acetylcholine and bradykinin also had good agreement. CONCLUSION: There were no differences between acetylcholine and bradykinin as venodilators in this endothelial venous function investigation.

  3. Stretching exercises enhance vascular endothelial function and improve peripheral circulation in patients with acute myocardial infarction.

    Science.gov (United States)

    Hotta, Kazuki; Kamiya, Kentaro; Shimizu, Ryosuke; Yokoyama, Misako; Nakamura-Ogura, Misao; Tabata, Minoru; Kamekawa, Daisuke; Akiyama, Ayako; Kato, Michitaka; Noda, Chiharu; Matsunaga, Atsuhiko; Masuda, Takashi

    2013-01-01

    The purpose of this study was to clarify the acute effects of a single session of stretching exercises on vascular endothelial function and peripheral circulation in patients with acute myocardial infarction. This study evaluated 32 patients (mean age, 66 ± 9 years) who received phase I cardiac rehabilitation after acute myocardial infarction. Five types of stretching exercises were performed on the floor: wrist dorsiflexion, close-legged trunk flexion, open-legged trunk flexion, open-legged lateral trunk bending, and cross-legged trunk flexion. Each exercise entailed a 30-second stretching followed by a 30-second relaxation, and was repeated twice. Low- and high-frequency components (LF and HF) of heart rate variability (LF, 0.04-0.15 Hz; HF, 0.15-0.40 Hz) were analyzed, and HF and LF/HF were used as indices of parasympathetic and sympathetic nervous activities, respectively. Reactive hyperemia peripheral arterial tonometry (RH-PAT) index was measured and used as a parameter for vascular endothelial function. Transcutaneous oxygen pressure (tcPO2) on the right foot and chest was also measured, and the Foot-tcPO2/Chest-tcPO2 ratio was used as a parameter for peripheral circulation. The HF, RH-PAT index, and Foot-tcPO2/Chest-tcPO2 ratio were significantly higher after the exercises than before (P after stretching exercises. These findings demonstrate that stretching exercises improve vascular endothelial function and peripheral circulation in patients with acute myocardial infarction.

  4. Chronic treatment with paeonol improves endothelial function in mice through inhibition of endoplasmic reticulum stress-mediated oxidative stress.

    Directory of Open Access Journals (Sweden)

    Ker Woon Choy

    endothelial function and normalized blood pressure in mice induced by tunicamycin in vivo through the inhibition of ER stress-associated ROS.

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

    Directory of Open Access Journals (Sweden)

    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 μM 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 μg/kg for two weeks, respectively, while paricalcitol at 0.042 μg/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.

  6. Impaired postprandial endothelial function depends on the type of fat consumed by healthy men.

    Science.gov (United States)

    Berry, Sarah E E; Tucker, Sally; Banerji, Radhika; Jiang, Benyu; Chowienczyk, Phillip J; Charles, Sonia M; Sanders, Thomas A B

    2008-10-01

    Postprandial lipemia impairs endothelial function possibly via an oxidative stress mechanism. A stearic acid-rich triacylglycerol (TAG) (shea butter) results in a blunted postprandial increase in plasma TAG compared with an oleic acid-rich TAG; however, its acute effects on endothelial function and oxidative stress are unknown. A randomized crossover trial (n = 17 men) compared the effects of 50 g fat, rich in stearic acid [shea butter blend (SA)] or oleic acid [high oleic sunflower oil (HO)], on changes in endothelial function [brachial artery flow-mediated dilatation (FMD)], arterial tone [pulse wave analysis (PWA), and carotid-femoral pulse wave velocity (PWV(c-f))], and oxidative stress (plasma 8-isoprostane F2alpha) at fasting and 3 h following the test meals. The postprandial increase in plasma TAG was lower (66% lower incremental area under curve) following the SA meal [28.3 (9.7, 46.9)] than after the HO meal [83.4 (57.0, 109.8); P < 0.001] (geometric means with 95% CI, arbitary units). Following the HO meal, there was a decrease in FMD [-3.0% (-4.4, -1.6); P < 0.001] and an increase in plasma 8-isoprostane F2alpha [10.4ng/L (3.8, 16.9); P = 0.005] compared with fasting values, but no changes followed the SA meal. The changes in 8-isoprostane F2alpha and FMD differed between meals and were 14.0 ng/L (6.4, 21.6; P = 0.001) and 1.75% (0.10, 3.39; P = 0.02), respectively. The reductions in PWA and PWV c-f did not differ between meals. This study demonstrates that a stearic acid-rich fat attenuates the postprandial impairment in endothelial function compared with an oleic acid-rich fat and supports the hypothesis that postprandial lipemia impairs endothelial function via an increase in oxidative stress.

  7. Maspin impairs the function of endothelial cells: an implying pathway of preeclampsia.

    Science.gov (United States)

    Zhang, Ying; Liu, Hao; Shi, Xinwei; Qiao, Fuyuan; Zeng, Wanjiang; Feng, Ling; Deng, Dongrui; Liu, Haiyi; Wu, Yuanyuan

    2017-09-29

    Widespread endothelial injury contributes to the occurrence of preeclampsia. Maspin, first identified as a tumor suppressor, plays a critical role in cell invasion and angiogenesis. Our previous studies found that the expression of maspin was increased in preeclampsic placenta. In this research, we studied the function of human umbilical vein endothelial cells (HUVECs) to explore the role and possible mechanism of maspin gene in the pathogenesis of preeclampsia. HUVECs were treated with different concentration of recombinant human maspin protein (r-maspin) during normoxia and hypoxia, we detected the proliferation, apoptosis, migration and tube formation of HUVECs. We also assessed nitride oxide (NO) synthesis and the expression of matrix metalloproteinase 2 (MMP2) to further explore the underlying molecular mechanism. There was only slight maspin expression at mRNA level in HUVECs. Treated HUVECs with r-maspin, the proliferation of HUVECs was significantly promoted both under normoxia and hypoxia. The tubes formed by HUVECs were significantly inhibited and NO synthesis was significantly reduced by r-maspin. Meantime, r-maspin also inhibited MMP2 expression and activity in HUVECs. However, there was no significant change in the migration and apoptosis of HUVECs. Maspin may be an important participant for mediating endothelial function and ultimately leads to the occurence of preeclamsia.

  8. Structural and functional characterization of endothelial microparticles released by cigarette smoke.

    Science.gov (United States)

    Serban, Karina A; Rezania, Samin; Petrusca, Daniela N; Poirier, Christophe; Cao, Danting; Justice, Matthew J; Patel, Milan; Tsvetkova, Irina; Kamocki, Krzysztof; Mikosz, Andrew; Schweitzer, Kelly S; Jacobson, Sean; Cardoso, Angelo; Carlesso, Nadia; Hubbard, Walter C; Kechris, Katerina; Dragnea, Bogdan; Berdyshev, Evgeny V; McClintock, Jeanette; Petrache, Irina

    2016-08-17

    Circulating endothelial microparticles (EMPs) are emerging as biomarkers of chronic obstructive pulmonary disease (COPD) in individuals exposed to cigarette smoke (CS), but their mechanism of release and function remain unknown. We assessed biochemical and functional characteristics of EMPs and circulating microparticles (cMPs) released by CS. CS exposure was sufficient to increase microparticle levels in plasma of humans and mice, and in supernatants of primary human lung microvascular endothelial cells. CS-released EMPs contained predominantly exosomes that were significantly enriched in let-7d, miR-191; miR-126; and miR125a, microRNAs that reciprocally decreased intracellular in CS-exposed endothelium. CS-released EMPs and cMPs were ceramide-rich and required the ceramide-synthesis enzyme acid sphingomyelinase (aSMase) for their release, an enzyme which was found to exhibit significantly higher activity in plasma of COPD patients or of CS-exposed mice. The ex vivo or in vivo engulfment of EMPs or cMPs by peripheral blood monocytes-derived macrophages was associated with significant inhibition of efferocytosis. Our results indicate that CS, via aSMase, releases circulating EMPs with distinct microRNA cargo and that EMPs affect the clearance of apoptotic cells by specialized macrophages. These targetable effects may be important in the pathogenesis of diseases linked to endothelial injury and inflammation in smokers.

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

    Science.gov (United States)

    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 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.

  10. Improved endothelialization of NiTi alloy by VEGF functionalized nanocoating.

    Science.gov (United States)

    Shen, Weixing; Cai, Kaiyong; Yang, Zaixiang; Yan, Ying; Yang, Weihu; Liu, Peng

    2012-06-01

    To improve surface endothelialization of NiTi alloy substrate, a nano-structured coating functionalized with vascular endothelial growth factor (VEGF) was fabricated via polydopamine (PDOP) as intermediate layer. The successful preparation of VEGF conjugated nanocoating was demonstrated by X-ray diffraction (XRD), atomic force microscope (AFM), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS), respectively. Inductively coupled plasma mass spectrometry (ICP-MS) test showed that the formed nanocoating significantly reduced the release of Ni ion from NiTi alloy in simulated body fluid. The biological behaviors of endothelial cells adhered to modified NiTi alloy substrates, including cell proliferation, cell spreading and production of nitric oxide and prostacyclin were investigated in vitro. The results suggest that surface functionalization of NiTi alloy substrate with VEGF is beneficial for cell growth. The approach presented here affords an alternative for surface modification of NiTi implants applied as heart and vascular implant devices. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Effect of high-intensity training on endothelial function in patients with cardiovascular and cerebrovascular disease

    DEFF Research Database (Denmark)

    Kolmos, Mia; Krawcyk, Rikke Steen; Kruuse, Christina

    2016-01-01

    was to gather current knowledge on the effects of high-intensity training versus moderate-intensity continuous exercise on endothelial function in cardiovascular and cerebrovascular patients. METHODS: A systematic review was performed in PubMed database, Embase and Cochrane libraries and on PEDro using...... the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were restricted to cardiovascular and cerebrovascular patients, and healthy subjects as general reference. Interventions comprised of high-intensity training alone, high-intensity training compared to moderate......OBJECTIVES: Exercise improves endothelial dysfunction, the key manifestation of cardiovascular and cerebrovascular disease, and is recommended in both cardiovascular and cerebrovascular rehabilitation. Disagreement remains, however, on the role of intensity of exercise. The purpose of this review...

  12. Endothelial function impairment in chronic venous insufficiency: effect of some cardiovascular protectant agents.

    Science.gov (United States)

    Carrasco, Omar F; Ranero, Alejandra; Hong, Enrique; Vidrio, Horacio

    In segments of human varicose veins, endothelial function was assessed by measuring relaxation induced by acetylcholine in noradrenaline-precontracted preparations. In addition, concentration-response curves to acetylcholine were obtained before and after incubation with the arterial endothelium protectant agents captopril, losartan, troglitazone, pravastatin, or simvastatin. The antivaricose agent escin was also tested. Mean acetylcholine-induced relaxation of varicose venous rings was about 13%, approximately one third of that reported for control saphenous veins. Concentration-response curves to acetylcholine were ''u'' shaped, the result of endothelium-mediated relaxation at low concentrations, superseded by subsequent smooth muscle contractile responses. Relaxation was enhanced by the endothelium-protecting agents and by escin, troglitazone being the least, and simvastatin the most effective. It was concluded that endothelial dysfunction is present in varicose veins, that this anomaly can be reverted by cardiovascular protecting agents, and that it can play a role in the pathogenesis and treatment of chronic venous insufficiency.

  13. Endothelial Function and Sleep: Associations of Flow-Mediated Dilation With Perceived Sleep Quality and Rapid Eye Movement (REM) Sleep

    OpenAIRE

    Cooper, Denise C.; Ziegler, Michael G.; Milic, Milos S.; Ancoli-Israel, Sonia; Mills, Paul J.; Loredo, José S.; von Känel, Roland; Dimsdale, Joel E.

    2013-01-01

    Endothelial function typically precedes clinical manifestations of cardiovascular disease and provides a potential mechanism for the associations observed between cardiovascular disease and sleep quality. This study examined how subjective and objective indicators of sleep quality relate to endothelial function, as measured by brachial artery flow-mediated dilation (FMD). In a clinical research centre, 100 non-shift working adults (mean age: 36 years) completed FMD testing and the Pittsburgh ...

  14. 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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    Dan T. Kho

    2017-09-01

    Full Text Available 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.

  15. 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.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  19. 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

  20. Can fish oil supplementation improve endothelial function in asymptomatic offspring of patients with peripheral arterial disease?

    Directory of Open Access Journals (Sweden)

    Spark JI

    2013-07-01

    Full Text Available J Ian Spark,1 Christopher L Delaney,1 Richard B Allan,1 Melissa HL Ho,2 Michelle D Miller21Department of Vascular Surgery, Flinders Medical Centre and Flinders University, 2Department of Nutrition and Dietetics, Flinders University, Bedford Park, Adelaide, South Australia, AustraliaBackground: Peripheral arterial disease affects 10%–25% of adults aged .55 years, and while a multitude of risk factors exist, one key influence is genetics. Rather than awaiting the onset of debilitating symptoms, interventions that target high-risk individuals and prevent or delay the onset of symptoms would have widespread impact. The aim of this study is to implement a 12-week fish oil intervention (10 mL/day containing approximately 1.5 g of eicosapentaenoic acid and 1 g of docosahexaenoic acid, with the intention of improving endothelial function, inflammation, and lipid status in a high-risk population, ie, those with impaired endothelial function and a parent with symptomatic peripheral arterial disease.Methods: This is a parallel-group, double-blind, randomized controlled trial involving administration of fish oil containing either about 1.5 g of docosahexaenoic acid and 1 g of docosahexaenoic acid (intervention or about 0.15 g of eicosapentaenoic acid and about 0.1 g of docosahexaenoic acid for 12 consecutive weeks (control. The participants are 100 offspring of adults with diagnosed peripheral arterial disease who themselves have an ankle-brachial pressure index ≥0.9 but impaired endothelial function according to peripheral arterial tonometry. Measures performed at baseline and at 6 and 12 weeks include flow-mediated dilatation, C-reactive protein, absolute neutrophil and lymphocyte counts, tumor necrosis factor-α, interleukin-1ß, and interleukin-6 levels, thromboxane and prostacyclin, lipid status, and homocysteine, nitrite, and nitrate levels. Participants will be phoned fortnightly to monitor adherence and side effects, while participants will

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

    Science.gov (United States)

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

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Endothelial function and carotid intima-media thickness in giant-cell arteritis.

    Science.gov (United States)

    Hafner, Franz; Haas, Elke; Belaj, Klara; Froehlich, Harald; Gary, Thomas; Eller, Philipp; Brodmann, Marianne

    2014-01-01

    Vascular endothelial dysfunction and intima-media thickness are characteristic aspects of several vasculitides. We investigated retrospectively the impact of steroid treatment on endothelial dysfunction and intima-media thickness in giant-cell arteritis. Forty-one patients with giant-cell arteritis (28 female and 13 male) underwent flow-mediated dilatation, a marker of endothelial function, and carotid intima-media thickness within 24 h after diagnosis and 6 months thereafter. Both parameters were investigated in 41 patients of an age- and gender-matched control group. Brachial flow-mediated dilatation response at baseline was 3.4% (0.2, 8.0) and 1.7% (0.2, 4.8) in giant-cell arteritis patients and control group, respectively. After 6 months treatment, flow-mediated dilatation response was 2.8% (0.4, 4.8) in patients with giant-cell arteritis (P = 0.066) and 1.4% (0.1, 5.5) in the control group (P = 0.741). In contrast, mean carotid intima-media thickness of giant-cell arteritis patients improved significantly between baseline [1.0 mm (0.79, 1.2)] and 6-month follow-up [0.82 mm (0.7, 1.04), P < 0.001]. Subjects with additional symptoms of polymyalgia rheumatica had a notable enlargement of carotid intima-media thickness [1.23 mm (1.14, 2.09)] compared to giant-cell arteritis patients without polymyalgia rheumatica at baseline [0.91 mm (0.76, 1.04), P = 0.001] and 6-month follow-up [1.16 mm (0.80, 1.26) vs. 0.77 mm (0.68, 0.88), P = 0.009]. Steroid therapy has no influence on endothelial function but does significantly improve carotid intima-media thickness in giant-cell arteritis. This divergence of endothelial function and intima-media thickness reflects the specifity of giant-cell arteritis for cerebrovascular arteries thereby sparing the brachial arteries. © 2013 Stichting European Society for Clinical Investigation Journal Foundation.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Consumption of high-polyphenol dark chocolate improves endothelial function in individuals with stage 1 hypertension and excess body weight.

    Science.gov (United States)

    Nogueira, Lívia de Paula; Knibel, Marcela Paranhos; Torres, Márcia Regina Simas Gonçalves; Nogueira Neto, José Firmino; Sanjuliani, Antonio Felipe

    2012-01-01

    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/m(2). 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.

  6. Effect of aging and dietary salt and potassium intake on endothelial PTEN (Phosphatase and tensin homolog on chromosome 10 function.

    Directory of Open Access Journals (Sweden)

    Wei-Zhong Ying

    Full Text Available Aging promotes endothelial dysfunction, defined as a reduction in bioavailable nitric oxide (NO produced by the endothelial isoform of nitric oxide synthase (NOS3. This enzyme is critically regulated by phosphorylation by protein kinase B (Akt, which in turn is regulated by the lipid phosphatase, PTEN. The present series of studies demonstrated a reduction in bioavailable NO as the age of rats increased from 1 to 12 months. At 12 months of age, rats no longer demonstrated increases in phosphorylated NOS3 in response to high dietary salt intake. Endothelial cell levels of PTEN increased with age and became refractory to change with increased salt intake. In contrast to the reduction in NO production, endothelial cell production of transforming growth factor-ß (TGF-ß relative to NO increased progressively with age. In macrovascular endothelial cells, PTEN was regulated in a dose-dependent fashion by TGF-ß, which was further regulated by extracellular [KCl]. When combined with prior studies, the present series of experiments suggested an integral role for PTEN in endothelial cell pathobiology of aging and an important mitigating function of TGF-ß in endothelial PTEN regulation. The findings further supported a role for diet in affecting vascular function through the production of TGF-ß and NO.

  7. Functional consequences of prolactin signalling in endothelial cells: a potential link with angiogenesis in pathophysiology?

    Science.gov (United States)

    Reuwer, Anne Q; Nowak-Sliwinska, Patrycja; Mans, Laurie A; van der Loos, Chris M; von der Thüsen, Jan H; Twickler, Marcel Th B; Spek, C Arnold; Goffin, Vincent; Griffioen, Arjan W; Borensztajn, Keren S

    2012-01-01

    Prolactin is best known as the polypeptide anterior pituitary hormone, which regulates the development of the mammary gland. However, it became clear over the last decade that prolactin contributes to a broad range of pathologies, including breast cancer. Prolactin is also involved in angiogenesis via the release of pro-angiogenic factors by leukocytes and epithelial cells. However, whether prolactin also influences endothelial cells, and whether there are functional consequences of prolactin-induced signalling in the perspective of angiogenesis, remains so far elusive. In the present study, we show that prolactin induces phosphorylation of ERK1/2 and STAT5 and induces tube formation of endothelial cells on Matrigel. These effects are blocked by a specific prolactin receptor antagonist, del1-9-G129R-hPRL. Moreover, in an in vivo model of the chorioallantoic membrane of the chicken embryo, prolactin enhances vessel density and the tortuosity of the vasculature and pillar formation, which are hallmarks of intussusceptive angiogenesis. Interestingly, while prolactin has only little effect on endothelial cell proliferation, it markedly stimulates endothelial cell migration. Again, migration was reverted by del1-9-G129R-hPRL, indicating a direct effect of prolactin on its receptor. Immunohistochemistry and spectral imaging revealed that the prolactin receptor is present in the microvasculature of human breast carcinoma tissue. Altogether, these results suggest that prolactin may directly stimulate angiogenesis, which could be one of the mechanisms by which prolactin contributes to breast cancer progression, thereby providing a potential tool for intervention. PMID:22128761

  8. Impaired endothelial function in patients with cryptogenic stroke and patent foramen ovale is not affected by closure.

    Science.gov (United States)

    Lantz, Maria; Kostulas, Konstantinos; Settergren, Magnus; Sjöstrand, Christina

    2017-06-01

    Patent foramen ovale (PFO) is associated with cryptogenic stroke (CS) and migraine with aura (MA). Endothelial dysfunction (ED) is a risk factor for development of cardiovascular disease, but might also be involved in migraine pathophysiology. Short-term worsening of migraine has been described after closure of PFO. We evaluated endothelial function in patients with CS and PFO, before and after closure of PFO, and in patients with migraine, whether changes in endothelial function was related to a change in migraine frequency. Patients with CS and PFO were included; 20 with planned closure of PFO and seven controls on medical treatment only. Endothelial function was assessed by peripheral arterial tonometry (EndoPat R ) and biomarkers of endothelial activation. Patients were followed longitudinally at baseline, day 1, 1 month, and 6 months. A headache diary was used to assess migraine frequency. Mean age of the cohort was 45.4 years, and migraine prevalence was 50% whereof 84.6% had MA. Median EndoPat R index (RHI) at baseline was 1.60 (IQR 1.41-2.00). There was no change in RHI over time, either in closure patients (P = 0.66), nor in controls (P = 0.31), and there was no change in biomarkers of endothelial activation. Three migraine patients experienced worsening of migraine frequency directly after closure. Endothelial function did not change after closure of PFO. Although patients were lacking cardiovascular risk factors, a high proportion had impaired endothelial function. Whether ED can have predictive value, identifying PFO at higher risk for recurrent stroke warrants further investigations. © 2017, Wiley Periodicals, Inc.

  9. Normalization methods in time series of platelet function assays

    Science.gov (United States)

    Van Poucke, Sven; Zhang, Zhongheng; Roest, Mark; Vukicevic, Milan; Beran, Maud; Lauwereins, Bart; Zheng, Ming-Hua; Henskens, Yvonne; Lancé, Marcus; Marcus, Abraham

    2016-01-01

    Abstract Platelet function can be quantitatively assessed by specific assays such as light-transmission aggregometry, multiple-electrode aggregometry measuring the response to adenosine diphosphate (ADP), arachidonic acid, collagen, and thrombin-receptor activating peptide and viscoelastic tests such as rotational thromboelastometry (ROTEM). The task of extracting meaningful statistical and clinical information from high-dimensional data spaces in temporal multivariate clinical data represented in multivariate time series is complex. Building insightful visualizations for multivariate time series demands adequate usage of normalization techniques. In this article, various methods for data normalization (z-transformation, range transformation, proportion transformation, and interquartile range) are presented and visualized discussing the most suited approach for platelet function data series. Normalization was calculated per assay (test) for all time points and per time point for all tests. Interquartile range, range transformation, and z-transformation demonstrated the correlation as calculated by the Spearman correlation test, when normalized per assay (test) for all time points. When normalizing per time point for all tests, no correlation could be abstracted from the charts as was the case when using all data as 1 dataset for normalization. PMID:27428217

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

    DEFF Research Database (Denmark)

    Gliemann, Lasse; Rytter, Nicolai; Lindskrog, Mads

    2017-01-01

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

  11. Treating normal early gestation placentae with preeclamptic sera produces extracellular micro and nano vesicles that activate endothelial cells.

    Science.gov (United States)

    Xiao, Xirong; Xiao, Fengyi; Zhao, Mingzhi; Tong, Mancy; Wise, Michelle R; Stone, Peter R; Chamley, Lawrence W; Chen, Qi

    2017-04-01

    Preeclampsia is characterised by systemic endothelial cell dysfunction thought to be triggered by toxic/dangerous factors from the placenta, including placental extracellular vesicles (EVs). Why placental EVs become toxic is unknown. We previously reported that preeclamptic sera produced toxic/dangerous placental macrovesicles but whether small EVs are also toxic/dangerous in preeclampsia is unknown. First trimester placental explants were treated with 10% preeclamptic or control sera (n=10) for 24h. Micro- and nano-vesicles were harvested by sequential centrifugation. Micro- or nano-vesicles were also exposed to monolayers of endothelial cells in the presence or absence of nifedipine (50μg/ml) or labetalol (0.5μg/ml) which are well-known anti-hypertensives in clinical practices. The number and size of micro- and nano-vesicles were counted. Endothelial cell-surface intercellular adhesion molecule 1 (ICAM-1) and high mobility group box 1 (HMGB1) levels in micro- or nano-vesicles were measured by immunoassays. Neither the amount nor size of both micro- and nano-vesicles was different after treating placental explants with preeclamptic or control sera. The levels of HMGB1 were significantly increased in both micro- and nano-vesicles from preeclamptic sera treated placental explants (pvesicles from preeclamptic sera-treated placental explants induced endothelial activation, but it was reversed by co-incubation with nifedipine (p=0.004) or labetalol (p=0.002). Our data demonstrate that preeclamptic sera produce toxic/dangerous micro- and nano-placental EVs which activated endothelial cells. This effect was reversed by antihypertensives. The increased levels of HMGB1 in EVs may contribute to endothelial cell activation. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. The effect of exercise intensity on endothelial function in physically inactive lean and obese adults.

    Directory of Open Access Journals (Sweden)

    Rachel Hallmark

    Full Text Available To examine the effects of exercise intensity on acute changes in endothelial function in lean and obese adults.Sixteen lean (BMI 30, age 26 ± 6 yr physically inactive adults were studied during 3 randomized admissions [control (C, no exercise, moderate-intensity exercise (M, @ lactate threshold (LT and high-intensity exercise (H, midway between LT and VO2peak (30 min]. Endothelial function was assessed by flow-mediated dilation (FMD at baseline and 1, 2, and 4 h post-exercise.RM ANCOVA revealed significant main effects for group, time, and group x condition interaction (p<0.05. A diurnal increase in FMD was observed in lean but not obese subjects. Lean subjects exhibited greater increases in FMD than obese subjects (p = 0.0005. In the obese group a trend was observed for increases in FMD at 2- and 4-hr after M (p = 0.08. For lean subjects, FMD was significantly elevated at all time points after H. The increase in FMD after H in lean subjects (3.2 ± 0.5% was greater than after both C (1.7 ± 0.4%, p = 0.015 and M (1.4 ± 0.4%, p = 0.002. FMD responses of lean and obese subjects significantly differed after C and H, but not after M.In lean young adults, high-intensity exercise acutely enhances endothelial function, while moderate-intensity exercise has no significant effect above that seen in the absence of exercise. The FMD response of obese adults is blunted compared to lean adults. Diurnal variation should be considered when examining the effects of acute exercise on FMD.

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

    Science.gov (United States)

    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.

  14. Q192R Paraoxonase (PON)1 Polymorphism, Insulin Sensitivity, and Endothelial Function in Essential Hypertensive Men.

    Science.gov (United States)

    Dell'Omo, Giulia; Penno, Giuseppe; Pucci, Laura; Lucchesi, Daniela; Del Prato, Stefano; Pedrinelli, Roberto

    2014-01-01

    Essential hypertension is characterized by increased reactive oxygen species (ROS) generation harmful for insulin sensitivity and nitric oxide (NO)-mediated vasomotor function, a noxious effect that paraoxonase (PON)1, an antioxidant circulating high-density lipoprotein (HDL)-bound esterase, may counteract. The PON1 gene contains several polymorphisms including a glutamine (Q) to arginine (R) transition at position 192 encoding circulating allozymes with higher antioxidant activity that might influence both parameters. Q192R was determined by polymerase chain reaction in 72 never-treated, glucose-tolerant, uncomplicated essential hypertensive men. Insulin sensitivity was assessed by homeostasis model assessment (HOMA) and endothelial function by forearm vasodilation (strain-gage venous plethysmography) to intra-arterial acetylcholine (ACH) with sodium nitroprusside (NIP) as a NO-independent control. Additional evaluation variables included 24-hour blood pressure (BP), lipids, BMI, smoking status, and metabolic syndrome (MetS) by Adult Treatment Panel (ATP)-III criteria. R192 was considered as the rare allele, and its associations analyzed by dominant models (Q/Q vs. Q/R + R/R). Genotype frequencies were consistent with the Hardy-Weinberg equilibrium. HOMA was lower and insulin resistance (the upper fourth of HOMA values distribution) less prevalent in Q/R + R/R carriers in whom ACH-mediated vasodilatation was greater and endothelial dysfunction (the bottom fourth of ACH(AUC) values distribution) less frequent than in Q/Q homozygotes. Q192R polymorphism and MetS were unrelated parameters despite their common association with insulin resistance. 24-hour BP, BMI, lipids, and smoking habits were homogeneously distributed across genotypes. Q192R polymorphism associates differentially with insulin sensitivity and endothelial function in essential hypertensive men.

  15. Q192R Paraoxonase (PON)1 Polymorphism, Insulin Sensitivity, and Endothelial Function in Essential Hypertensive Men

    Science.gov (United States)

    Dell’Omo, Giulia; Penno, Giuseppe; Pucci, Laura; Lucchesi, Daniela; Prato, Stefano Del; Pedrinelli, Roberto

    2014-01-01

    AIMS Essential hypertension is characterized by increased reactive oxygen species (ROS) generation harmful for insulin sensitivity and nitric oxide (NO)-mediated vasomotor function, a noxious effect that paraoxonase (PON)1, an antioxidant circulating high-density lipoprotein (HDL)-bound esterase, may counteract. The PON1 gene contains several polymorphisms including a glutamine (Q) to arginine (R) transition at position 192 encoding circulating allozymes with higher antioxidant activity that might influence both parameters. METHODS Q192R was determined by polymerase chain reaction in 72 never-treated, glucose-tolerant, uncomplicated essential hypertensive men. Insulin sensitivity was assessed by homeostasis model assessment (HOMA) and endothelial function by forearm vasodilation (strain-gage venous plethysmography) to intra-arterial acetylcholine (ACH) with sodium nitroprusside (NIP) as a NO-independent control. Additional evaluation variables included 24-hour blood pressure (BP), lipids, BMI, smoking status, and metabolic syndrome (MetS) by Adult Treatment Panel (ATP)-III criteria. R192 was considered as the rare allele, and its associations analyzed by dominant models (Q/Q vs. Q/R + R/R). RESULTS Genotype frequencies were consistent with the Hardy–Weinberg equilibrium. HOMA was lower and insulin resistance (the upper fourth of HOMA values distribution) less prevalent in Q/R + R/R carriers in whom ACH-mediated vasodilatation was greater and endothelial dysfunction (the bottom fourth of ACHAUC values distribution) less frequent than in Q/Q homozygotes. Q192R polymorphism and MetS were unrelated parameters despite their common association with insulin resistance. 24-hour BP, BMI, lipids, and smoking habits were homogeneously distributed across genotypes. CONCLUSIONS Q192R polymorphism associates differentially with insulin sensitivity and endothelial function in essential hypertensive men. PMID:25089090

  16. Low-Normal Thyroid Function and Novel Cardiometabolic Biomarkers

    NARCIS (Netherlands)

    van Tienhoven-Wind, Lynnda J. N.; Dullaart, Robin P. F.

    The concept is emerging that low-normal thyroid function, i.e., either higher thyroid-stimulating hormone or lower free thyroxine levels within the euthyroid reference range, could contribute to the development of atherosclerotic cardiovascular disease. It is possible that adverse effects of

  17. Normal left ventricular function does not protect against propafenone ...

    African Journals Online (AJOL)

    Normal left ventricular function does not protect against propafenone-induced incessant ventricular tachycardia. R. N. Scott Millar, J. B. Lawrenson, D.A. Milne. Abstract. Propafenone is a class Ic anti-arrhythmic agent with mild B-blocking properties which has recently become available in South Africa. We have used the ...

  18. Functional stability of endothelial cells on a novel hybrid scaffold for vascular tissue engineering

    International Nuclear Information System (INIS)

    Pankajakshan, Divya; Krishnan, Lissy K; Krishnan V, Kalliyana

    2010-01-01

    Porous and pliable conduits made of biodegradable polymeric scaffolds offer great potential for the development of blood vessel substitutes but they generally lack signals for cell proliferation, survival and maintenance of a normal phenotype. In this study we have prepared and evaluated porous poly(ε-caprolactone) (PCL) integrated with fibrin composite (FC) to get a biomimetic hybrid scaffold (FC PCL) with the biological properties of fibrin, fibronectin (FN), gelatin, growth factors and glycosaminoglycans. Reduced platelet adhesion on a human umbilical vein endothelial cell-seeded hybrid scaffold as compared to bare PCL or FC PCL was observed, which suggests the non-thrombogenic nature of the tissue-engineered scaffold. Analysis of real-time polymerase chain reaction (RT-PCR) after 5 days of endothelial cell (EC) culture on a hybrid scaffold indicated that the prothrombotic von Willebrand factor and plasminogen activator inhibitor (PAI) were quiescent and stable. Meanwhile, dynamic expressions of tissue plasminogen activator (tPA) and endothelial nitric oxide synthase indicated the desired cell phenotype on the scaffold. On the hybrid scaffold, shear stress could induce enhanced nitric oxide release, which implicates vaso-responsiveness of EC grown on the tissue-engineered construct. Significant upregulation of mRNA for extracellular matrix (ECM) proteins, collagen IV and elastin, in EC was detected by RT-PCR after growing them on the hybrid scaffold and FC-coated tissue culture polystyrene (FC TCPS) but not on FN-coated TCPS. The results indicate that the FC PCL hybrid scaffold can accomplish a remodeled ECM and non-thrombogenic EC phenotype, and can be further investigated as a scaffold for cardiovascular tissue engineering. (communication)

  19. Effect of Ivabradine on Endothelial Function in Diastolic and Right Heart Failure Patients

    Directory of Open Access Journals (Sweden)

    Arturo Orea-Tejeda

    2013-01-01

    Full Text Available Background. Ivabradine is an If ion current inhibitor that has proved to reduce mortality in patients with systolic heart failure by slowing heart rate without decreasing myocardial contractility. Photoplethysmography is a simple, low-cost optical technique that can evaluate vascular function and detect changes in blood flow, pulse, and swelling of tissular microvascular space. Objective. To evaluate the effect of ivabradine on endothelial function by photoplethysmography in diastolic and right heart failure patients. Methodology. 15 patients were included (mean age of 78.1 ± 9.2 years with optimally treated diastolic and right heart failure. They underwent photoplethysmography before and after induced ischemia to evaluate the wave blood flow on the finger, using the maximum amplitude time/total time (MAT/TT index. Two measurements were made before and after oral Ivabradine (mean 12.5 mg a day during 6 months of followup. Results. In the study group, the MAT/TT index was 29.1 ± 2.2 versus 24.3 ± 3.2 ( in basal recording and 30.4 ± 2.1 versus 23.3 ± 2.9 (, before versus after ischemia and before versus after Ivabradine intervention, respectively. Conclusions. Ivabradine administration improves endothelial function (shear stress in diastolic and right heart failure patients.

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

    Science.gov (United States)

    Wang, Xiaoyin; Derakhshandeh, Ronak; Liu, Jiangtao; Narayan, Shilpa; Nabavizadeh, Pooneh; Le, Stephenie; Danforth, Olivia M; Pinnamaneni, Kranthi; Rodriguez, Hilda J; Luu, Emmy; Sievers, Richard E; Schick, Suzaynn F; Glantz, Stanton A; Springer, Matthew L

    2016-07-27

    Despite public awareness that tobacco secondhand smoke (SHS) is harmful, many people still assume that marijuana SHS is benign. Debates about whether smoke-free laws should include marijuana are becoming increasingly widespread as marijuana is legalized and the cannabis industry grows. Lack of evidence for marijuana SHS causing acute cardiovascular harm is frequently mistaken for evidence that it is harmless, despite chemical and physical similarity between marijuana and tobacco smoke. We investigated whether brief exposure to marijuana SHS causes acute vascular endothelial dysfunction. We measured endothelial function as femoral artery flow-mediated dilation (FMD) in rats before and after exposure to marijuana SHS at levels similar to real-world tobacco SHS conditions. One minute of exposure to marijuana SHS impaired FMD to a comparable extent as impairment from equal concentrations of tobacco SHS, but recovery was considerably slower for marijuana. Exposure to marijuana SHS directly caused cannabinoid-independent vasodilation that subsided within 25 minutes, whereas FMD remained impaired for at least 90 minutes. Impairment occurred even when marijuana lacked cannabinoids and rolling paper was omitted. Endothelium-independent vasodilation by nitroglycerin administration was not impaired. FMD was not impaired by exposure to chamber air. One minute of exposure to marijuana SHS substantially impairs endothelial function in rats for at least 90 minutes, considerably longer than comparable impairment by tobacco SHS. Impairment of FMD does not require cannabinoids, nicotine, or rolling paper smoke. Our findings in rats suggest that SHS can exert similar adverse cardiovascular effects regardless of whether it is from tobacco or marijuana. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  1. 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.

  2. The evaluation of endothelial function and structure in hirsute patients in reproductive age.

    Science.gov (United States)

    Atasayan, Kemal; Yoldemir, Tevfik; Ramoglu, Sedef; Yavuz, Dilek Gogas

    2016-11-01

    To evaluate the endothelial function and structure in patients with hirsutism in reproductive age. The study was conducted on 69 consecutive women admitted with complaints of hirsutism and 63 voluntary healthy women, as controls. A total of 132 subjects who applied to the Gynecology and Infertility Outpatient Clinics were included. Participants with modified Ferriman Gallway (mFG) score over 8 were considered to be hirsute. The demographic, metabolic, hormonal characteristics, risk factors of cardiovascular disease, CIMT (carotis intima media thickness) and FMD (flow-mediated dilatation) were compared between hirsute women and those in the control group. A prospective case-control study was performed. There was no statistically significant difference in CIMT (0,50±0,08 vs 0,52±0,08, p=0.38) and FMD (10,80±6,83 vs 9,57±6,52, p=0.34) values between the study and control groups, respectively. There was no statistically significant correleation between CIMT and FMD values with age, body mass index (BMI), waist circumference, hip circumference, waist/hip ratio, CRP (C-reactive protein), total cholesterol, LDL (low density lipoprotein), HDL (high density lipoprotein), total testosteron, FAI (free androjen index), androstenedion, SHBG (sex hormone binding globuline), DHEA-S, hirsutism score, sistolic blood pressure, diastolic blood pressure, HOMA-IR (homeostatic model of assesment insuline resistance) value. The effect of the presence of hirsutism on either CIMT and FMD values, among young patients was not significant. Since endothelial dysfunction might became evident after a long period of physio-pathological process, our findings obtained from younger patients may not really show the impact of hirsutism on endothelial function in short term. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Κ-opioid receptor stimulation improves endothelial function in hypoxic pulmonary hypertension.

    Directory of Open Access Journals (Sweden)

    Qi Wu

    Full Text Available The present study was designed to investigate the effect of κ-opioid receptor stimulation with U50,488H on endothelial function and underlying mechanism in rats with hypoxic pulmonary hypertension (HPH. Chronic hypoxia-induced HPH was simulated by exposing the rats to 10% oxygen for 2 wk. After hypoxia, mean pulmonary arterial pressure (mPAP, right ventricular pressure (RVP and right ventricular hypertrophy index (RVHI were measured. Relaxation of pulmonary artery in response to acetylcholine (ACh was determined. Expression and activity of endothelial nitric oxide (NO synthase (eNOS and inducible NO synthase (iNOS with NO production, total antioxidant capacity (T-AOC, gp91(phox expression and nitrotyrosine content were measured. The effect of U50,488H administration during chronic hypoxia was investigated. Administration of U50,488H significantly decreased mPAP and right ventricular hypertrophy as evidenced by reduction in RVP and RVHI. These effects were mediated by κ-opioid receptor. In the meantime, treatment with U50,488H significantly improved endothelial function as evidenced by enhanced relaxation in response to ACh. Moreover, U50,488H resulted in a significant increase in eNOS phosphorylation, NO content in serum, and T-AOC in pulmonary artery of HPH rats. In addition, the activity of eNOS was enhanced, but the activity of iNOS was attenuated in the pulmonary artery of chronic hypoxic rats treated with U50,488H. On the other hand, U50,488H markedly blunted HPH-induced elevation of gp91(phox expression and nitrotyrosine content in pulmonary artery, and these effects were blocked by nor-BNI, a selective κ-opioid receptor antagonist. These data suggest that κ-opioid receptor stimulation with U50,488H improves endothelial function in rats with HPH. The mechanism of action might be attributed to the preservation of eNOS activity, enhancement of eNOS phosphorylation, downregulation of iNOS activity and its antioxidative/nitrative effect.

  5. Does cognitive function predict frequency compressed speech recognition in listeners with normal hearing and normal cognition?

    Science.gov (United States)

    Ellis, Rachel J; Munro, Kevin J

    2013-01-01

    The aim was to investigate the relationship between cognitive ability and frequency compressed speech recognition in listeners with normal hearing and normal cognition. Speech-in-noise recognition was measured using Institute of Electrical and Electronic Engineers sentences presented over earphones at 65 dB SPL and a range of signal-to-noise ratios. There were three conditions: unprocessed, and at frequency compression ratios of 2:1 and 3:1 (cut-off frequency, 1.6 kHz). Working memory and cognitive ability were measured using the reading span test and the trail making test, respectively. Participants were 15 young normally-hearing adults with normal cognition. There was a statistically significant reduction in mean speech recognition from around 80% when unprocessed to 40% for 2:1 compression and 30% for 3:1 compression. There was a statistically significant relationship between speech recognition and cognition for the unprocessed condition but not for the frequency-compressed conditions. The relationship between cognitive functioning and recognition of frequency compressed speech-in-noise was not statistically significant. The findings may have been different if the participants had been provided with training and/or time to 'acclimatize' to the frequency-compressed conditions.

  6. Normalization.

    Science.gov (United States)

    Cuevas, Eduardo J.

    1997-01-01

    Discusses cornerstone of Montessori theory, normalization, which asserts that if a child is placed in an optimum prepared environment where inner impulses match external opportunities, the undeviated self emerges, a being totally in harmony with its surroundings. Makes distinctions regarding normalization, normalized, and normality, indicating how…

  7. Propionyl-L-carnitine improves endothelial function, microcirculation and pain management in critical limb ischemia.

    Science.gov (United States)

    De Marchi, S; Zecchetto, S; Rigoni, A; Prior, M; Fondrieschi, L; Scuro, A; Rulfo, F; Arosio, E

    2012-10-01

    Chronic critical limb ischemia (CLI) is a severe condition of hypo-perfusion of lower limbs, which is associated with inflammation and a pro-coagulative state. It is a disease at high risk of amputation and cardiovascular death. Propionyl-L-carnitine (PLC) is efficacious in improving pain free walking distance in peripheral arterial disease with claudication; it also exerts favorable effects on the arterial wall and on endothelial function. The purpose of this study was to evaluate the effects of PLC on microcirculation, endothelial function and pain relief in patients affected by CLI not suitable for surgical intervention. We enrolled 48 patients with CLI. Patients were randomized into two groups: the first group was treated with PLC, the second was treated with saline solution. All of them underwent the following tests: laser Doppler flowmetry at the forefoot at rest and after ischemia, trans cutaneous oxygen partial pressure and carbon dioxide partial pressure at the forefoot at rest and after ischemia, endothelium dependent dilation of the brachial artery. All tests were repeated after treatments. Pain was assessed by visual analog pain scale. Endothelium dependent dilation increased after PLC (9.5 ± 3.2 vs 4.9 ± 1.4 %; p production decreased after PLC. VAS showed a significant reduction in pain perception after active treatment. In CLI patients, PLC can improve microcirculation (post ischemic hyperemia, TcPO2 and TcPCO2 production). PLC also enhances endothelium dependent dilation and reduces analgesic consumption and pain perception.

  8. Sparstolonin B inhibits pro-angiogenic functions and blocks cell cycle progression in endothelial cells.

    Science.gov (United States)

    Bateman, Henry R; Liang, Qiaoli; Fan, Daping; Rodriguez, Vanessa; Lessner, Susan M

    2013-01-01

    Sparstolonin B (SsnB) is a novel bioactive compound isolated from Sparganium stoloniferum, an herb historically used in Traditional Chinese Medicine as an anti-tumor agent. Angiogenesis, the process of new capillary formation from existing blood vessels, is dysregulated in many pathological disorders, including diabetic retinopathy, tumor growth, and atherosclerosis. In functional assays, SsnB inhibited endothelial cell tube formation (Matrigel method) and cell migration (Transwell method) in a dose-dependent manner. Microarray experiments with human umbilical vein endothelial cells (HUVECs) and human coronary artery endothelial cells (HCAECs) demonstrated differential expression of several hundred genes in response to SsnB exposure (916 and 356 genes, respectively, with fold change ≥2, pcell types showed significant overlap, including genes associated with cell proliferation and cell cycle. Flow cytometric cell cycle analysis of HUVECs treated with SsnB showed an increase of cells in the G1 phase and a decrease of cells in the S phase. Cyclin E2 (CCNE2) and Cell division cycle 6 (CDC6) are regulatory proteins that control cell cycle progression through the G1/S checkpoint. Both CCNE2 and CDC6 were downregulated in the microarray data. Real Time quantitative PCR confirmed that gene expression of CCNE2 and CDC6 in HUVECs was downregulated after SsnB exposure, to 64% and 35% of controls, respectively. The data suggest that SsnB may exert its anti-angiogenic properties in part by downregulating CCNE2 and CDC6, halting progression through the G1/S checkpoint. In the chick chorioallantoic membrane (CAM) assay, SsnB caused significant reduction in capillary length and branching number relative to the vehicle control group. Overall, SsnB caused a significant reduction in angiogenesis (ANOVA, p<0.05), demonstrating its ex vivo efficacy.

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

    Science.gov (United States)

    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.

  10. Impaired vascular endothelial function in patients with restless legs syndrome: a new aspect of the vascular pathophysiology.

    Science.gov (United States)

    Koh, Seung Yon; Kim, Min Seung; Lee, Sun Min; Hong, Ji Man; Yoon, Jung Han

    2015-12-15

    Restless legs syndrome (RLS) is a common sleep disorder in which patients feel unpleasant leg sensations and the urge to move their legs during rest, particularly at night. Leg movement improves these symptoms. Although several studies have demonstrated an association between cardiovascular disease and RLS, the mechanisms underlying this relationship remain unclear. Recent studies have shown changes in the peripheral microvasculature, including altered blood flow and capillary tortuosity, and peripheral hypoxia. Vascular endothelial dysfunction can be assessed noninvasively with ultrasound measurements of brachial artery flow-mediated dilatation (FMD). Therefore, this study investigated FMD in RLS patients to determine the involvement of microvascular alterations in this disorder. The study enrolled 25 drug-naïve RLS patients and 25 sex- and age-matched controls and compared the FMD values of the two groups. RLS was diagnosed according to the criteria of the International Restless Legs Syndrome Study Group. FMD was significantly lower in the RLS patients (6.6 ± 1.2%) compared to the controls (8.4 ± 1.8%; p<0.05) and the RLS patients showed a weak, negative correlation between RLS severity and FMD (r=-0.419, p=0.04). Multivariate linear regression analysis revealed that RLS (B=-1.87, 95% confidence interval [CI] -2.72 to -1.02; p<0.001) and age (B=-0.06; 95% CI -0.12 to -0.02; p<0.001) were significantly and inversely correlated with FMD. This study demonstrated that RLS patients have poorer vascular endothelial function than normal healthy subjects and provides further evidence supporting the involvement of peripheral systems in the generation of RLS. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Normal family of meromorphic functions concerning fixed-points

    Science.gov (United States)

    Fang, Caiyun; Xu, Yan

    2017-09-01

    Let A>1 be a constant and F be a family of meromorphic functions defined in a domain D. For each f\\in F , f has only zeros of multiplicity at least 3 and satisfies the following conditions: (1) |f^' ' ' }(z)|≤ A|z| when f(z)=0 ; (2) f^' ' ' }(z)≠ z ; (3) all poles of f are multiple. In this paper, we characterize the non-normal sequences of F.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Comparing the Effects of Krebs Plus Verapamil Solution on Endothelial Function of Harvested Human Greater Saphenous Vein with Heparinized Blood, an Invitro Study.

    Science.gov (United States)

    Shokri, Mitra; Moradpour, Reza; Shafaroudi, Majid Malekzade; Rezaei, Nourollah; Tabary, Shervin Ziabakhsh

    2017-06-01

    Integrity of the great saphenous vein (GSV) endothelium is the most important key element for long-term patency rate of grafts in coronary artery bypass graft (CABG). Storage solutions play an important role in maintaining viability of vein endothelium. Diminished nitric oxide (NO) because of endothelial dysfunction may facilitate vascular inflammation and formation of atherosclerotic plaque. So, we decided to find a reasonable alternative preservative solution instead of heparinized blood (HB) by measuring NO concentration with Griess assay. SVG samples were obtained from 54 patients undergoing elective CABG. 3 mm rings were stored in solutions: heparinized blood (HB), Krebs (K), Krebs + Propranolol (K+P) 6.66 g/l, Krebs + Adrenaline (K+A) 200 µl/l, and Krebs + Verapamil (K+V) 200 µl/l for 30, 45, 60 and 90 min. Nitrite concentration was measured by Griess assay at 540 nm. H&E staining was performed for histologic test. Statistical analysis was performed using SPSS (V16). Results were expressed as (Means ± SE) followed by One-Way ANOVA for finding best preservative solution. Repeated measurement test was used to investigate best time. In all analysis, (PHB=K=K+A=K+P). Also, our investigations showed that NO concentration in (K+V) has the highest rate in time 90 min (10.07±0.56, p=0.002):. More than 50 percent of endothelial cells stay normal in (K+V) compare with other solutions. It seems that (K+V) is the best solution for the maintenance of normal physiology of SVGs endothelial cells. The most appropriate SVGs endothelial function is within 90 minutes after harvesting.

  14. Normalization of the collage regions of iterated function systems

    Science.gov (United States)

    Zhang, Zhengbing; Zhang, Wei

    2012-11-01

    Fractal graphics, generated with iterated function systems (IFS), have been applied in broad areas. Since the collage regions of different IFS may be different, it is difficult to respectively show the attractors of iterated function systems in a same region on a computer screen using one program without modifying the display parameters. An algorithm is proposed in this paper to solve this problem. A set of transforms are repeatedly applied to modify the coefficients of the IFS so that the collage region of the resulted IFS changes toward the unit square. Experimental results demonstrate that the collage region of any IFS can be normalized to the unit square with the proposed method.

  15. 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

    AIM: 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 endothelial function in patients with type 2 diabetes. METHOD: 24 patients with type 2 diabetes were randomized to receive either 200 mg metoprolol succinate or 50 mg carvedilol daily. Endothelium-dependent vasodilation was assessed by using venous occlusion plethysmography with increasing doses of intra...... with metoprolol, the percentage change in forearm blood-flow was 60.19% +/- 17.89 (at the highest serotonin dosages) before treatment and -33.80% +/- 23.38 after treatment (p = 0.007). Treatment with carvedilol did not change insulin-stimulated endothelial function. Endothelium-dependent vasodilation without...

  16. Rescue of Brain Function Using Tunneling Nanotubes Between Neural Stem Cells and Brain Microvascular Endothelial Cells.

    Science.gov (United States)

    Wang, Xiaoqing; Yu, Xiaowen; Xie, Chong; Tan, Zijian; Tian, Qi; Zhu, Desheng; Liu, Mingyuan; Guan, Yangtai

    2016-05-01

    Evidence indicates that neural stem cells (NSCs) can ameliorate cerebral ischemia in animal models. In this study, we investigated the mechanism underlying one of the neuroprotective effects of NSCs: tunneling nanotube (TNT) formation. We addressed whether the control of cell-to-cell communication processes between NSCs and brain microvascular endothelial cells (BMECs) and, particularly, the control of TNT formation could influence the rescue function of stem cells. In an attempt to mimic the cellular microenvironment in vitro, a co-culture system consisting of terminally differentiated BMECs from mice in a distressed state and NSCs was constructed. Additionally, engraftment experiments with infarcted mouse brains revealed that control of TNT formation influenced the effects of stem cell transplantation in vivo. In conclusion, our findings provide the first evidence that TNTs exist between NSCs and BMECs and that regulation of TNT formation alters cell function.

  17. Calcium and electrical signaling in arterial endothelial tubes: New insights into cellular physiology and cardiovascular function.

    Science.gov (United States)

    Behringer, Erik J

    2017-04-01

    The integral role of the endothelium during the coordination of blood flow throughout vascular resistance networks has been recognized for several decades now. Early examination of the distinct anatomy and physiology of the endothelium as a signaling conduit along the vascular wall has prompted development and application of an intact endothelial "tube" study model isolated from rodent skeletal muscle resistance arteries. Vasodilatory signals such as increased endothelial cell (EC) Ca 2+ ([Ca 2+ ] i ) and hyperpolarization take place in single ECs while shared between electrically coupled ECs through gap junctions up to distances of millimeters (≥2 mm). The small- and intermediate-conductance Ca 2+ activated K + (SK C a /IK C a or K C a 2.3/K C a 3.1) channels function at the interface of Ca 2+ signaling and hyperpolarization; a bidirectional relationship whereby increases in [Ca 2+ ] i activate SK C a /IK C a channels to produce hyperpolarization and vice versa. Further, the spatial domain of hyperpolarization among electrically coupled ECs can be finely tuned via incremental modulation of SK C a /IK C a channels to balance the strength of local and conducted electrical signals underlying vasomotor activity. Multifunctional properties of the voltage-insensitive SK C a /IK C a channels of resistance artery endothelium may be employed for therapy during the aging process and development of vascular disease. © 2016 John Wiley & Sons Ltd.

  18. [Expression and function of receptors for advanced glycation end products in bovine corneal endothelial cells].

    Science.gov (United States)

    Kaji, Yuichi

    2005-11-01

    Corneal endothelial cell loss is a change that occurs with age, but its mechanism is still unclear. We postulated that interaction between advanced glycation end product(AGE) and its receptors is implicated in the corneal endothelial cell loss with age. We investigated the expression of AGE receptors: receptors for AGE(RAGE) and galectin-3 in bovine corneal endothelial cells by reverse transcription-polymerase chain reaction(RT-PCR) and immunohistochemistry. In addition, we investigated the effect of AGE on the cultured corneal endothelial cells. Expression of RAGE and galectin-3 was detected in bovine corneal endothelial cells. Galectin-3 was important in the internalization of AGE. In contrast, RAGE was important in the generation of reactive oxygen species and induction of apoptosis. Based on these data, the interaction of AGE in aqueous humor and AGE receptors expressed on the corneal endothelial cells was speculated to have a role in the corneal endothelial cell loss with age.

  19. Sex differences in normal age trajectories of functional brain networks.

    Science.gov (United States)

    Scheinost, Dustin; Finn, Emily S; Tokoglu, Fuyuze; Shen, Xilin; Papademetris, Xenophon; Hampson, Michelle; Constable, R Todd

    2015-04-01

    Resting-state functional magnetic resonance image (rs-fMRI) is increasingly used to study functional brain networks. Nevertheless, variability in these networks due to factors such as sex and aging is not fully understood. This study explored sex differences in normal age trajectories of resting-state networks (RSNs) using a novel voxel-wise measure of functional connectivity, the intrinsic connectivity distribution (ICD). Males and females showed differential patterns of changing connectivity in large-scale RSNs during normal aging from early adulthood to late middle-age. In some networks, such as the default-mode network, males and females both showed decreases in connectivity with age, albeit at different rates. In other networks, such as the fronto-parietal network, males and females showed divergent connectivity trajectories with age. Main effects of sex and age were found in many of the same regions showing sex-related differences in aging. Finally, these sex differences in aging trajectories were robust to choice of preprocessing strategy, such as global signal regression. Our findings resolve some discrepancies in the literature, especially with respect to the trajectory of connectivity in the default mode, which can be explained by our observed interactions between sex and aging. Overall, results indicate that RSNs show different aging trajectories for males and females. Characterizing effects of sex and age on RSNs are critical first steps in understanding the functional organization of the human brain. © 2014 Wiley Periodicals, Inc.

  20. Functions of autophagy in normal and diseased liver

    Science.gov (United States)

    Czaja, Mark J.; Ding, Wen-Xing; Donohue, Terrence M.; Friedman, Scott L.; Kim, Jae-Sung; Komatsu, Masaaki; Lemasters, John J.; Lemoine, Antoinette; Lin, Jiandie D.; Ou, Jing-hsiung James; Perlmutter, David H.; Randall, Glenn; Ray, Ratna B.; Tsung, Allan; Yin, Xiao-Ming

    2013-01-01

    Autophagy has emerged as a critical lysosomal pathway that maintains cell function and survival through the degradation of cellular components such as organelles and proteins. Investigations specifically employing the liver or hepatocytes as experimental models have contributed significantly to our current knowledge of autophagic regulation and function. The diverse cellular functions of autophagy, along with unique features of the liver and its principal cell type the hepatocyte, suggest that the liver is highly dependent on autophagy for both normal function and to prevent the development of disease states. However, instances have also been identified in which autophagy promotes pathological changes such as the development of hepatic fibrosis. Considerable evidence has accumulated that alterations in autophagy are an underlying mechanism of a number of common hepatic diseases including toxin-, drug- and ischemia/reperfusion-induced liver injury, fatty liver, viral hepatitis and hepatocellular carcinoma. This review summarizes recent advances in understanding the roles that autophagy plays in normal hepatic physiology and pathophysiology with the intent of furthering the development of autophagy-based therapies for human liver diseases. PMID:23774882

  1. Ruthenium Complex Improves the Endothelial Function in Aortic Rings From Hypertensive Rats.

    Science.gov (United States)

    Vatanabe, Izabela Pereira; Rodrigues, Carla Nascimento Dos Santos; Buzinari, Tereza Cristina; Moraes, Thiago Francisco de; Silva, Roberto Santana da; Rodrigues, Gerson Jhonatan

    2017-06-29

    The endothelium is a monolayer of cells that extends on the vascular inner surface, responsible for the modulation of vascular tone. By means of the release of nitric oxide (NO), the endothelium has an important protective function against cardiovascular diseases. Verify if cis- [Ru(bpy)2(NO2)(NO)](PF6)2 (BPY) improves endothelial function and the sensibility of conductance (aorta) and resistance (coronary) to vascular relaxation induced by BPY. Normotensive (2K) and hypertensive (2K-1C) Wistar rats were used. For vascular reactivity study, thoracic aortas were isolated, rings with intact endothelium were incubated with: BPY(0.01 to10 µM) and concentration effect curves to acetylcholine were performed. In addition, cumulative concentration curves were performed to BPY (1.0 nM to 0.1 µM) in aortic and coronary rings, with intact and denuded endothelium. In aorta from 2K-1C animals, the treatment with BPY 0.1µM increased the potency of acetylcholine-induced relaxation and it was able to revert the endothelial dysfunction. The presence of the endothelium did not modify the effect of BPY in inducing the relaxation in aortas from 2K and 2K-1C rats. In coronary, the endothelium potentiated the vasodilator effect of BPY in vessels from 2K and 2K-1C rats. Our results suggest that 0.1 µM of BPY is able to normalize the relaxation endothelium dependent in hypertensive rats, and the compound BPY induces relaxation in aortic from normotensive and hypertensive rats with the same potency. The endothelium potentiate the relaxation effect induced by BPY in coronary from normotensive and hypertensive rats, with lower effect on coronary from hypertensive rats. O endotélio é uma monocamada de células que se estende sobre a superfície interna vascular, responsável pela modulação do tônus vascular. Por meio da liberação de óxido nítrico (NO), o endotélio tem uma função protetora importante contra doenças cardiovasculares. Verificar se o cis- [Ru (BPY)2 (NO2) (NO

  2. 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...

  3. 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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

  5. Influence of Adjuvant Therapy in Cancer Survivors on Endothelial Function and Skeletal Muscle Deoxygenation.

    Directory of Open Access Journals (Sweden)

    Austin K Ederer

    Full Text Available The cardiotoxic effects of adjuvant cancer treatments (i.e., chemotherapy and radiation treatment have been well documented, but the effects on peripheral cardiovascular function are still unclear. We hypothesized that cancer survivors i would have decreased resting endothelial function; and ii altered muscle deoxygenation response during moderate intensity cycling exercise compared to cancer-free controls. A total of 8 cancer survivors (~70 months post-treatment and 9 healthy controls completed a brachial artery FMD test, an index of endothelial-dependent dilation, followed by an incremental exercise test up to the ventilatory threshold (VT on a cycle ergometer during which pulmonary V̇O2 and changes in near-infrared spectroscopy (NIRS-derived microvascular tissue oxygenation (TOI, total hemoglobin concentration ([Hb]total, and muscle deoxygenation ([HHb] ≈ fractional O2 extraction were measured. There were no significant differences in age, height, weight, and resting blood pressure between cancer survivors and control participants. Brachial artery FMD was similar between groups (P = 0.98. During exercise at the VT, TOI was similar between groups, but [Hb]total and [HHb] were significantly decreased in cancer survivors compared to controls (P < 0.01 The rate of change for TOI (ΔTOIΔ/V̇O2 and [HHb] (Δ[HHb]/ΔV̇O2 relative to ΔV̇O2 were decreased in cancer survivors compared to controls (P = 0.02 and P = 0.03 respectively. In cancer survivors, a decreased skeletal muscle microvascular function was observed during moderate intensity cycling exercise. These data suggest that adjuvant cancer therapies have an effect on the integrated relationship between O2 extraction, V̇O2 and O2 delivery during exercise.

  6. Effects of atorvastatin and vitamin C on endothelial function of hypercholesterolemic patients.

    Science.gov (United States)

    Perticone, F; Ceravolo, R; Maio, R; Cloro, C; Candigliota, M; Scozzafava, A; Mongiardo, A; Mastroroberto, P; Chello, M; Mattioli, P L

    2000-10-01

    We tested the effects of vitamin C and atorvastatin treatment on endothelium-dependent and endothelium-independent vasodilation in 18 hypercholesterolemic patients (ten men and eight women, aged 20-46 years) in comparison with 12 normal volunteers (seven men and five women, aged 20-45 years). The responses of the forearm blood flow (FBF) to acetylcholine (ACh) (7.5, 15 and 30 microg/min), sodium nitroprusside (SNP) (0.8, 1.6, 3.2 microg/min) and L-NMMA (2, 4, 8 micromol/min) were evaluated at baseline and after 1 month of atorvastatin (10 mg/day) treatment. Drugs were infused into the brachial artery and FBF was measured by strain-gauge plethysmography. At baseline, the response to ACh was significantly attenuated in hypercholesterolemics versus controls: at the highest dose (30 microg/min), FBF was 27.0+/-3.4 versus 11.5+/-1.9 ml.100 ml tissue(-1).min(-1) respectively (P<0.0001). No significant differences were found between groups during SNP infusion. The atorvastatin treatment significantly improved ACh-stimulated FBF: at highest dose the FBF increased to 14.9+/-1.5 ml.100 ml tissue(-1). min(-1) (P<0.0001). Similarly, the L-NMMA endothelial effects were significantly enhanced by lipid-lowering treatment, supporting the improvement of basal nitric oxide. Vitamin C increased ACh-vasodilation in the same way before and after atorvastatin treatment. In conclusion, the endothelial dysfunction in hypercholesterolemics is due to an oxidative stress and atorvastatin rapidly improves both basal and stimulated endothelium-dependent vasodilation.

  7. Progesterone therapy, endothelial function and cardiovascular risk factors: a 3-month randomized, placebo-controlled trial in healthy early postmenopausal women.

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    Jerilynn C Prior

    Full Text Available BACKGROUND: Progesterone is effective treatment for hot flushes/night sweats. The cardiovascular effects of progesterone therapy are unknown but evidence suggests that premenopausal normal estradiol with also normal progesterone levels may provide later cardiovascular protection. We compared the effects of progesterone to placebo on endothelial function, weight, blood pressure, metabolism, lipids, inflammation and coagulation. METHODS AND RESULTS: We conducted a randomized, double-blind, 3-month placebo-controlled trial of progesterone (300 mg daily among 133 healthy postmenopausal women in Vancouver, Canada from 2003-2009. Endothelial function by venous occlusion plethysmography was a planned primary outcome. Enrolled women were 1-11 y since last menstruation, not using hormones (for >6 months, non-smoking, without diabetes, hypertension, heart disease or their medications. Randomized (1∶1 women (55 ± 4 years, body mass index 25 ± 3 initially had normal blood pressure, fasting lipid, glucose and electrocardiogram results. Endothelial function (% forearm blood flow above saline was not changed with progesterone (487 ± 189%, n = 18 compared with placebo (408 ± 278%, n = 16 (95% CI diff [-74 to 232], P = 0.30. Progesterone (n = 65 and placebo (n = 47 groups had similar changes in systolic and diastolic blood pressure, resting heart rate, weight, body mass index, waist circumference, total cholesterol, low-density lipoprotein cholesterol and triglyceride levels. High-density lipoprotein was lower (-0.14 mmol/L, P = 0.001 on progesterone compared with placebo. Fasting glucose, hs-C-reactive protein, albumin and D-dimer changes were all comparable to placebo. Framingham General Cardiovascular Risk Profile scores were initially low and remained low with progesterone therapy and not statistically different from placebo. CONCLUSIONS: Results indicate that progesterone has short-term cardiovascular safety. Endothelial

  8. 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...... 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....... plethysmography. Insulin-stimulated endothelial function was assessed after intra-arterial infusion of insulin followed by co-infusion with serotonin in three different dosages. Forearm glucose uptake was measured during the insulin infusion. RESULTS: Patients with systolic heart failure had impaired insulin...

  9. MicroRNA-200a is up-regulated in aged rats with erectile dysfunction and could attenuate endothelial function via SIRT1 inhibition

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    Feng Pan

    2016-01-01

    Full Text Available MiR-200a was shown to be upregulated in the corpus cavernosum (CC of rats with aging-related erectile dysfunction (A-ED in our previous study. Among its target genes, SIRT1 was also reported as a protective factor in erectile function by our groups previously. Thus, miR-200a might attenuate the erectile function in A-ED via SIRT1 inhibition. In the present study, three animal groups were included: aged rats with ED (group AE, n = 8, aged rats with normal erectile function (group AN, n = 8, and young rats as normal controls (group YN, n = 8. CCs from each group were collected for histological and molecular measurements to validate the dysregulation of miR-200a and SIRT1. After that, the cavernous endothelial cells (CECs from CC of aged rats with normal erectile function were transfected with miR-200a in vitro. Then the expression of SIRT1 and molecules within the eNOS/NO/PKG pathway were measured to investigate whether the transfection could imitate the attenuated process of erectile function in the aged. As a result, miR-200a was upregulated while the SIRT1, the levels of eNOS and cGMP were all downregulated in the CCs from AE group. After transfection in vitro, the miR-200a was upregulated while the SIRT1 and levels of eNOS and cGMP were obviously downregulated. Finally, based on the results of our previous study, we further verify that up-regulation of miR-200a could participate in the mechanisms of A-ED via SIRT1 inhibition, and mainly attenuate endothelial function via influencing the eNOS/NO/PKGpathway.

  10. Fish oil supplementation improves endothelial function in normoglycemic offspring of patients with type 2 diabetes

    Science.gov (United States)

    Rizza, Stefano; Tesauro, Manfredi; Cardillo, Carmine; Galli, Angelica; Iantorno, Micaela; Gigli, Fabrizio; Sbraccia, Paolo; Federici, Massimo; Quon, Michael J.; Lauro, Davide

    2009-01-01

    Objective Offspring of patients with type 2 diabetes (OPDs) exhibits endothelial dysfunction (ED) associated with a chronic inflammatory state. N-3 polyunsaturated fatty acids (n-3 PUFA) may have antioxidant and anti-inflammatory properties that are beneficial for cardiovascular and metabolic health. Therefore, in the present study, we tested the hypothesis that dietary supplementation with fish oil rich in n-3 PUFA may improve ED in otherwise healthy OPDs. Methods and design A double-blind, placebo-controlled trial was conducted with 50 OPDs. Participants were randomized to treatment with either placebo or n-3 PUFA (2 g/day) for 12 weeks. Before and after treatment we evaluated endothelial function (using flow-mediated dilation (FMD) of the brachial artery), circulating inflammatory markers (adiponectin, TNF-α, and high sensitivity-CRP), and insulin resistance (QUICKI). Results No significant changes were observed in study outcomes in subjects treated with placebo. By contrast, when compared with baseline values, subjects treated with n-3 PUFA had significant improvement in FMD (9.1 ± 5.8% vs. 11.7 ± 4.4%, p = 0.02) that was accompanied by decreased plasma triglycerides (117 ± 73 mg/dl vs. 86 ± 44 mg/dl, p = 0.001) and TNF-α levels (8.9 ± 2.3 pg/ml vs. 6.8 ± 2.7 pg/ml, p = 0.001), and a trend towards increased plasma adiponectin levels (7.8 ± 4.5 μg/ml vs. 9.5 ± 5.1 μg/ml, p = 0.09). When data were analyzed by multiple regression analysis, decreased TNF-α after treatment with n-3 PUFA predicted increased FMD. Conclusion Dietary supplementation with n-3 PUFA significantly improved endothelial function and reduced pro-inflammatory markers in OPDs. Thus, fish oil consumption may have beneficial cardiovascular and metabolic health effects in otherwise healthy subjects predisposed to diabetes and its vascular complications. PMID:19394939

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

    Science.gov (United States)

    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.

  12. Bubble formation and endothelial function before and after 3 months of dive training.

    Science.gov (United States)

    Pontier, Jean-Michel; Guerrero, François; Castagna, Olivier

    2009-01-01

    It has been suggested that repeated compression-decompression cycles reduce diver susceptibility to decompression sickness (DCS). This study examined whether intensive scuba dive training would reduce bubble formation and modulate endothelial function as shown by skin circulation. There were 22 military divers who were studied before and after a 90-d program of physical training and open-sea air diving (mean 67 dives total). Skin blood flow in the forearm was measured at rest (baseline), during post-occlusive hyperemia (endothelium-dependent vasodilatation), and with local heating to 42 degrees C (maximal vasodilatation). Subjects were also examined by pulsed Doppler for venous bubbles 30, 60, and 90 min after surfacing from a hyperbaric exposure to 400 kPa (30 msw) for 30 min in a dry chamber. None of the divers experienced DCS during the training period. There was no change in weight, body mass index, maximal oxygen uptake, or endothelial function. Bubble grades by the Kisman Integrated Severity Score were significantly decreased immediately after the diving training period (3.6 +/- 9.2 vs. 16.4 +/- 14.3) and increased 3 mo after this period (10.3 +/- 13.9 vs. 3.6 +/- 9.2). The results highlight that repeated scuba dives and regular physical exercise activity reduce bubble formation and probably have a protective effect against DCS risk. Although this phenomenon has been observed for decades, the mechanism remains complex and the results cannot elucidate the effects of physical exercise and NO production. Bubble formation could activate the stress response which could be the basis for diving acclimatization.

  13. Effects of black raspberry on lipid profiles and vascular endothelial function in patients with metabolic syndrome.

    Science.gov (United States)

    Jeong, Han Saem; Hong, Soon Jun; Lee, Tae-Bum; Kwon, Ji-Wung; Jeong, Jong Tae; Joo, Hyung Joon; Park, Jae Hyoung; Ahn, Chul-Min; Yu, Cheol Woong; Lim, Do-Sun

    2014-10-01

    Black raspberry (Rubus occidentalis) has been known for its anti-inflammatory and anti-oxidant effects. However, short-term effects of black raspberry on lipid profiles and vascular endothelial function have not been investigated in patients with metabolic syndrome. Patients with metabolic syndrome (n = 77) were prospectively randomized into a group with black raspberry (n = 39, 750 mg/day) and a placebo group (n = 38) during a 12-week follow-up. Lipid profiles, brachial artery flow-mediated dilatation (baFMD), and inflammatory cytokines such as IL-6, TNF-α, C-reactive protein, adiponectin, sICAM-1, and sVCAM-1 were measured at the baseline and at the 12-week follow-up. Decreases from the baseline in the total cholesterol level (-22.8 ± 30.4 mg/dL vs. -1.9 ± 31.8 mg/dL, p raspberry than in the placebo group. Increases in baFMD at the 12-week follow-up were significantly greater in the group with black raspberry than in the placebo group (0.33 ± 0.44 mm vs. 0.10 ± 0.35 mm, p raspberry. The use of black raspberry significantly decreased serum total cholesterol level and inflammatory cytokines, thereby improving vascular endothelial function in patients with metabolic syndrome during the 12-week follow-up. Copyright © 2014 John Wiley & Sons, Ltd.

  14. Effect of Danshen injection on the vascular endothelial function and renal function in patients with pregnancy induced hypertension syndrome

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    Jun-Qing Zhang

    2016-12-01

    Full Text Available Objective: To explore the effect of Danshen injection on the vascular endothelial function and renal function in patients with pregnancy induced hypertension syndrome (PIH. Methods: A total of 100 patients with PIH who were admitted in our hospital from May, 2015 to May, 2016 were included in the study and randomized into the observation group and the control group. The patients in the control group were given blood pressure reduction, diuresis, spasmolysis, sedation, magnesium sulfate, and comprehensive nursing intervention. On this basis, the patients in the observation group were given additional Danshen injection (20 mL + 5% glucose (250 mL, ivdrip, 1 time/d. After 10 d treatment, the efficacy was evaluated. The peripheral venous blood before and after treatment in the two groups was collected. The radioimmunoassay was used to detect ET-1. ELISA was used to detect Hcy. The immunoturbidimetry was used to detect vWF. The radioimmunoassay was used to detect BUN, Scr, UA, and β2-MG. The standard sphygmomanometer was used to monitor the blood pressure and MAP was calculated. The biuret colorimetry was used to determine 24 h Upro. Results: The reduced degree of ET-1, Hcy, and vWF after treatment in the observation group was significantly superior to that in the control group. The reduced degree of BUN, Scr, UA, and β2-MG after treatment in the observation group was significantly superior to that in the control group. The reduced degree of MPA and 24 h Upro after treatment in the observation group was significantly superior to that in the control group. Conclusions: Routine treatments, comprehensive nursing intervention, and Danshen injection in the treatment of PIH can effectively improve the vascular endothelial function and renal function in order to reduce the blood pressure and alleviate the urine protein.

  15. Vascular surgical stretch injury leads to activation of P2X7 receptors and impaired endothelial function.

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    Padmini Komalavilas

    Full Text Available A viable vascular endothelial layer prevents vasomotor dysfunction, thrombosis, inflammation, and intimal hyperplasia. Injury to the endothelium occurs during harvest and "back table" preparation of human saphenous vein prior to implantation as an arterial bypass conduit. A subfailure overstretch model of rat aorta was used to show that subfailure stretch injury of vascular tissue leads to impaired endothelial-dependent relaxation. Stretch-induced impaired relaxation was mitigated by treatment with purinergic P2X7 receptor (P2X7R inhibitors, brilliant blue FCF (FCF and A740003, or apyrase, an enzyme that catalyzes the hydrolysis of ATP. Alternatively, treatment of rat aorta with exogenous ATP or 2'(3'-O-(4-Benzoyl benzoyl-ATP (BzATP also impaired endothelial-dependent relaxation. Treatment of human saphenous vein endothelial cells (HSVEC with exogenous ATP led to reduced nitric oxide production which was associated with increased phosphorylation of the stress activated protein kinase, p38 MAPK. ATP- stimulated p38 MAPK phosphorylation of HSVEC was inhibited by FCF and SB203580. Moreover, ATP inhibition of nitric oxide production in HSVEC was prevented by FCF, SB203580, L-arginine supplementation and arginase inhibition. Finally, L-arginine supplementation and arginase inhibition restored endothelial dependent relaxation after stretch injury of rat aorta. These results suggest that vascular stretch injury leads to ATP release, activation of P2X7R and p38 MAPK resulting in endothelial dysfunction due to arginase activation. Endothelial function can be restored in both ATP treated HSVEC and intact stretch injured rat aorta by P2X7 receptor inhibition with FCF or L-arginine supplementation, implicating straightforward therapeutic options for treatment of surgical vascular injury.

  16. Effects of functional olive oil enriched with its own phenolic compounds on endothelial function in hypertensive patients. A randomised controlled trial.

    Science.gov (United States)

    Valls, Rosa-M; Farràs, Marta; Suárez, Manuel; Fernández-Castillejo, Sara; Fitó, Montserrat; Konstantinidou, Valentini; Fuentes, Francisco; López-Miranda, José; Giralt, Montserrat; Covas, María-Isabel; Motilva, María-José; Solà, Rosa

    2015-01-15

    The additional health-promoting properties of functional virgin olive oil (FVOO) enriched with its own phenolic compounds (OOPC) versus the parental virgin olive oil (VOO) must be tested in appropriate human clinical trials. Our aim was to assess the effects of FVOO on endothelial function in hypertensive patients. Thirteen pre- and stage-1 hypertensive patients received a single dose of 30 mL of FVOO (OOPC=961 mg/kg) or VOO (OOPC=289 mg/kg) in a postprandial randomised, double blind, crossover trial. Endothelial function, measured as ischemic reactive hyperemia (IRH) and related biomarkers, were followed for 5h after consumption. Compared with VOO, FVOO increased IRH (Pbenefits on endothelial function than a standard natural virgin olive oil in pre- and hypertensive patients. isrctn.org. Identifier ISRCTN03450153. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. [Infection of Mice with Normal Immune Function by Taenia asiatica].

    Science.gov (United States)

    Liu, Xiao-yan; Guo, Guang-wu; Chen, Li-hong; Mo, Xing-ze; Yu, Yue-sheng

    2015-08-01

    The Taenia asiatica eggs pre-incubated with sodium hypochlorite solution for 4 min, 6 min and 8 mins were subcutaneously injected into mice with normal immune function(groups Al-A3 respectively, n=20 in each) and mice with immunosuppression (groups B1-B3, n=20 in each). All groups of mice began to show body discomfort on day 5 after infection and develop lumps on the back about on day 15. In groups Al-A3, animal death occurred during days 7-15, with a same survival rate of 95.0%(19/20) and infection rate of 89.4%(17/19), 73.6%(14/19) and 47.3%(9/19) respectively. In groups B1-B3, animal death occurred during days 7-50, with survival rate of 60%(13/20), 55%(11/20)and 55%(11/20) and infection rate of 76.9% (10/13), 54.5% (6/11) and 45.4% (5/11) respectively. After the scolex of cysticercus was evaginated with 15% pig bile, four suckers, an apparent rostellum and two distinct hook-like puncta structures were seen. These results indicate that mice with normal immune function can be used as a replacement of immunosuppressive mice to establish a T. asiatica oncosphere infection model. In addition, the T. asiatica eggs pre-incubated with sodium hypochlorite solution for 4 min have the strongest infection ability.

  18. New Indices of Endothelial Function Measured by Digital Thermal Monitoring of Vascular Reactivity: Data from 6084 Patients Registry

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    Morteza Naghavi

    2016-01-01

    Full Text Available Background. Endothelial function is viewed as a barometer of cardiovascular health and plays a central role in vascular reactivity. Several studies showed digital thermal monitoring (DTM as a simple noninvasive method to measure vascular reactivity that is correlated with atherosclerosis risk factors and coronary artery disease. Objectives. To further evaluate the relations between patient characteristics and DTM indices in a large patient registry. Methods. DTM measures were correlated with age, sex, heart rate, and systolic and diastolic blood pressure in 6084 patients from 18 clinics. Results. DTM vascular reactivity index (VRI was normally distributed and inversely correlated with age (r=-0.21, p<0.0001. Thirteen percent of VRI tests were categorized as poor vascular reactivity (VRI < 1.0, 70 percent as intermediate (1.0 ≤ VRI < 2.0, and 17 percent as good (VRI ≥ 2.0. Poor VRI (<1.0 was noted in 6% of <50 y, 10% of 50–70 y, and 18% of ≥70 y. In multiple linear regression analyses, age, sex, and diastolic blood pressure were significant but weak predictors of VRI. Conclusions. As the largest database of finger-based vascular reactivity measurement, this report adds to prior findings that VRI is a meaningful physiological marker and reflects a high level of residual risk found in patients currently under care.

  19. Changes in corneal sensation, epithelial damage, and tear function after descemet stripping automated endothelial keratoplasty.

    Science.gov (United States)

    Hirayama, Yumiko; Satake, Yoshiyuki; Hirayama, Masatoshi; Shimazaki-Den, Seika; Konomi, Kenji; Shimazaki, Jun

    2013-09-01

    To study the ocular surface changes in eyes after Descemet stripping automated endothelial keratoplasty (DSAEK) compared with those after penetrating keratoplasty (PKP). This prospective study compared the changes in 31 eyes of 28 patients who underwent DSAEK (DSAEK group) with those in 15 disease-matched eyes of 15 patients who underwent PKP (PKP group). Corneal epithelial integrity was evaluated using a fluorescein staining score. Corneal sensation was measured with a Cochet-Bonnet esthesiometer. Tear function was evaluated using the Schirmer test, tear clearance test, tear function index, and tear break-up time. The postoperative fluorescein staining score was significantly higher in the PKP group than in the DSAEK group (P = 0.02). Postoperative corneal sensation was significantly better in the DSAEK group than in the PKP group (P sensation after DSAEK was significantly better than the preoperative value (P = 0.02). There were no statistically significant changes in the Schirmer test, tear clearance test, tear function index, or break-up time before and after the surgery in both the DSAEK and PKP groups. No significant differences were observed between the DSAEK and PKP groups after the surgery. Corneal sensation was preserved, and epithelial damage was less severe after DSAEK compared with PKP. Preservation of corneal sensation may contribute to the early recovery of visual function and long-term maintenance of ocular surface health after DSAEK.

  20. Discovery and functional assessment of gene variants in the vascular endothelial growth factor pathway.

    Science.gov (United States)

    Paré-Brunet, Laia; Glubb, Dylan; Evans, Patrick; Berenguer-Llergo, Antoni; Etheridge, Amy S; Skol, Andrew D; Di Rienzo, Anna; Duan, Shiwei; Gamazon, Eric R; Innocenti, Federico

    2014-02-01

    Angiogenesis is a host-mediated mechanism in disease pathophysiology. The vascular endothelial growth factor (VEGF) pathway is a major determinant of angiogenesis, and a comprehensive annotation of the functional variation in this pathway is essential to understand the genetic basis of angiogenesis-related diseases. We assessed the allelic heterogeneity of gene expression, population specificity of cis expression quantitative trait loci (eQTLs), and eQTL function in luciferase assays in CEU and Yoruba people of Ibadan, Nigeria (YRI) HapMap lymphoblastoid cell lines in 23 resequenced genes. Among 356 cis-eQTLs, 155 and 174 were unique to CEU and YRI, respectively, and 27 were shared between CEU and YRI. Two cis-eQTLs provided mechanistic evidence for two genome-wide association study findings. Five eQTLs were tested for function in luciferase assays and the effect of two KRAS variants was concordant with the eQTL effect. Two eQTLs found in each of PRKCE, PIK3C2A, and MAP2K6 could predict 44%, 37%, and 45% of the variance in gene expression, respectively. This is the first analysis focusing on the pattern of functional genetic variation of the VEGF pathway genes in CEU and YRI populations and providing mechanistic evidence for genetic association studies of diseases for which angiogenesis plays a pathophysiologic role. © 2013 WILEY PERIODICALS, INC.

  1. 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.

  2. 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

    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...

  3. Effects of oral folic acid supplementation on endothelial function in familial hypercholesterolemia. A randomized placebo-controlled trial

    NARCIS (Netherlands)

    Verhaar, M. C.; Wever, R. M.; Kastelein, J. J.; van Loon, D.; Milstien, S.; Koomans, H. A.; Rabelink, T. J.

    1999-01-01

    Folates have been suggested to be of benefit in reducing cardiovascular risk. The present study was designed to examine whether oral folic acid supplementation could improve endothelial function as an intermediate end point for cardiovascular risk in patients with increased risk of atherosclerosis

  4. The Influence of Endothelial Function and Myocardial Ischemia on Peak Oxygen Consumption in Patients with Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Simon L. Bacon

    2012-01-01

    Full Text Available Impaired endothelial function has been shown to limit exercise in coronary artery disease (CAD patients and has been implicated in myocardial ischemia. However, the association of endothelial function and ischemia on peak exercise oxygen consumption (VO2 has not been previously reported. A total of 116 CAD patients underwent standard exercise stress testing, during which VO2 was measured. On a separate day, endothelial-dependent and -independent function were assessed by ultrasound using flow-mediated arterial vasodilation (FMD and sublingual glyceryl trinitrate administration (GTNMD of the brachial artery. Patients with exercise-induced myocardial ischemia had lower FMD than nonischemic patients (3.64±0.57 versus 4.98±0.36, P=.050, but there was no difference in GTNMD (14.11±0.99 versus 15.47±0.63, P=.249. Analyses revealed that both FMD (P=.006 and GTNMD (P=.019 were related to peak VO2. However, neither the presence of ischemia (P=.860 nor the interaction of ischemia with FMD (P=.382 and GTNMD (P=.151 was related to peak VO2. These data suggest that poor endothelial function, potentially via impaired NO production and smooth muscle dysfunction, may be an important determinant of exercise capacity in patients with CAD, independent of myocardial ischemia.

  5. 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.

  6. 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...

  7. Endothelial Functioning and Hemodynamic Parameters in Rats with Subclinical Hypothyroid and the Effects of Thyroxine Replacement.

    Directory of Open Access Journals (Sweden)

    Cuixia Gao

    Full Text Available Subclinical hypothyroidism (SCH and its associations with atherosclerosis (AS and cardiovascular disease remain controversial. The purpose of our study was to observe changes in endothelial functioning and hemodynamics in rats with SCH and to determine whether L-thyroxine (L-T4 administration affects these changes.In total, sixty male Wistar rats were randomly divided into the following three groups with 20 rats each: control euthyroid rats, SCH rats and SCH rats that had been treated with thyroxine (SCH+T4. The SCH rats were induced by administration of 10 mg x kg(-1 x d(-1 methimazole (MMI once daily by gavage for 3 months. The SCH+T4 rats were administered the same dose of MMI for three months in addition to 2 μg x kg(-1 x d(-1 L-T4 once daily by gavage after 45 days of MMI administration. The control rats received physiological saline via gavage.The SCH group had significantly higher thyroid-stimulating hormone (TSH, total cholesterol (TC, low-density lipoprotein cholesterol (LDL-C, and endothelin (ET levels and a lower nitric oxide (NO level than the control and SCH+T4 groups. The tail and carotid artery blood pressures, left ventricular systolic pressure, heart rate and aorta ventralis blood flow were significantly lower in the SCH group than in the control and SCH+T4 groups. ACH treatment caused concentration-dependent relaxation, which was reduced in the SCH arteries compared with the control and SCH+T4 arteries. Histopathological examination revealed the absence of pathological changes in the SCH rat arteries.These findings demonstrate that L-T4 treatment ameliorates endothelial dysfunction and hemodynamic changes in SCH rats.

  8. Aerobic Swim Training Restores Aortic Endothelial Function by Decreasing Superoxide Levels in Spontaneously Hypertensive Rats

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    Camila P. Jordão

    endothelial function.

  9. Endothelial Functioning and Hemodynamic Parameters in Rats with Subclinical Hypothyroid and the Effects of Thyroxine Replacement

    Science.gov (United States)

    Liu, Jing; Guo, Qian; Tian, Limin

    2015-01-01

    Objective Subclinical hypothyroidism (SCH) and its associations with atherosclerosis (AS) and cardiovascular disease remain controversial. The purpose of our study was to observe changes in endothelial functioning and hemodynamics in rats with SCH and to determine whether L-thyroxine (L-T4) administration affects these changes. Methods In total, sixty male Wistar rats were randomly divided into the following three groups with 20 rats each: control euthyroid rats, SCH rats and SCH rats that had been treated with thyroxine (SCH+T4). The SCH rats were induced by administration of 10 mg.kg-1.d-1 methimazole (MMI) once daily by gavage for 3 months. The SCH+T4 rats were administered the same dose of MMI for three months in addition to 2 μg.kg-1.d-1 L-T4 once daily by gavage after 45 days of MMI administration. The control rats received physiological saline via gavage. Results The SCH group had significantly higher thyroid-stimulating hormone (TSH), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and endothelin (ET) levels and a lower nitric oxide (NO) level than the control and SCH+T4 groups. The tail and carotid artery blood pressures, left ventricular systolic pressure, heart rate and aorta ventralis blood flow were significantly lower in the SCH group than in the control and SCH+T4 groups. ACH treatment caused concentration-dependent relaxation, which was reduced in the SCH arteries compared with the control and SCH+T4 arteries. Histopathological examination revealed the absence of pathological changes in the SCH rat arteries. Conclusions These findings demonstrate that L-T4 treatment ameliorates endothelial dysfunction and hemodynamic changes in SCH rats. PMID:26158620

  10. Effects of Exenatide vs. Metformin on endothelial function in obese patients with pre-diabetes: a randomized trial

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    Kelly Aaron S

    2012-06-01

    Full Text Available Abstract Background Glucagon like peptide-1 (GLP-1 receptor agonist treatment may improve endothelial function via direct and indirect mechanisms. We compared the acute and chronic effects of the GLP-1 receptor agonist exenatide vs. metformin on endothelial function in patients with obesity and pre-diabetes. Methods We performed a randomized, open-label, clinical trial in 50 non-diabetic individuals (mean age 58.5 ± 10.0; 38 females with abdominal obesity and either impaired fasting glucose, elevated HbA1c, or impaired glucose tolerance (IGT who were randomized to receive 3-months of exenatide or metformin. Microvascular endothelial function, assessed by digital reactive hyperemia (reactive hyperemic index: RHI, C-reactive protein (CRP, circulating oxidized LDL (oxLDL, and vascular cell adhesion molecule-1 (VCAM-1 were measured at baseline and 3-months. Seven subjects with IGT participated in a sub-study comparing the effects of pre-administration of exenatide and metformin on postprandial endothelial function. Results There were no differences for the change in RHI (Δ exenatide: 0.01 ± 0.68 vs. Δ metformin: -0.17 ± 0.72, P = 0.348, CRP, oxLDL, or VCAM-1 between exenatide and metformin treatment. Triglycerides were reduced more with exenatide compared to metformin (Δ exenatide: -25.5 ± 45.7 mg/dL vs. Δ metformin: -2.9 ± 22.8 mg/dL, P = 0.032. In the sub-study, there was no difference in postprandial RHI between exenatide and metformin. Conclusions Three months of exenatide therapy had similar effects on microvascular endothelial function, markers of inflammation, oxidative stress, and vascular activation, as metformin, in patients with obesity and pre-diabetes. Clinical trials registration This study is registered on http://www.clinicaltrials.gov/: NCT00546728

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

    Science.gov (United States)

    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.

  12. Relationship of endothelial dysfunction and kidney functional state in patients with systemic sclerosis

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    A M Basova

    2009-01-01

    Full Text Available Objective. To study vasoregulatory function of vascular wall in pts with systemic sclerosis (SS and chronic scleroderma-related renal disease (SRD and determine relationship with main measures of kidney functional state. Material and methods. 25 pts with SS (24 female with mean age 46,4±10,7 years and mean disease duration 7,5±4,7 years were included. 24 pts (96% had diffuse form and 17 pts (68% – generalized stage of SS. 22 pts (88% had chronic course of the disease with typical damage of vessels, heart, lungs and skin. SRD was revealed in 17 pts (68%. Sonographic method of Celermejer D. et al. (1992 was used for assessment of vascular endothelial function. 15 healthy persons without SS were included in control group. Results. Most prominent changes of brachial artery reactivity with insufficient vasodilatation and paradoxical vasoconstriction to reactive hyperemia were revealed in most pts with moderate and severe SRD. Conclusion. These changes of endothelium dependent and endothelium independent parameters in pts with SRD pointed to irreversible probably scleroderma-related vascular wall damage.

  13. Body composition, nutritional status, and endothelial function in physically active men without metabolic syndrome--a 25 year cohort study.

    Science.gov (United States)

    Pigłowska, Małgorzata; Kostka, Tomasz; Drygas, Wojciech; Jegier, Anna; Leszczyńska, Joanna; Bill-Bielecka, Mirosława; Kwaśniewska, Magdalena

    2016-04-27

    The purpose of this analysis was to investigate the relationship between body composition, metabolic parameters and endothelial function among physically active healthy middle-aged and older men. Out of 101 asymptomatic men prospectively tracked for traditional cardiovascular risk factors (mean observation period 25.1 years), 55 metabolically healthy individuals who maintained stable leisure time physical activity (LTPA) level throughout the observation and agreed to participate in the body composition assessment were recruited (mean age 60.3 ± 9.9 years). Body composition and raw bioelectrical parameters were measured with bioelectrical impedance analysis (BIA). Microvascular endothelial function was evaluated by means of the reactive hyperemia index (RHI) using Endo-PAT2000 system. Strong correlations were observed between lifetime physical activity (PA), aerobic fitness and most of analyzed body composition parameters. The strongest inverse correlation was found for fat mass (p metabolic parameters, HDL cholesterol (HDL-C) and uric acid were significantly associated with most body composition indicators. Regarding endothelial function, a negative correlation was found for RHI and body mass (p metabolic profile. Maintaining regular high PA level and metabolically healthy status through young and middle adulthood may have beneficial influence on body composition parameters and may prevent age-related decrease of fat-free mass and endothelial dysfunction.

  14. Impact of the DASH diet on endothelial function, exercise capacity, and quality of life in patients with heart failure.

    Science.gov (United States)

    Rifai, Luay; Pisano, Carol; Hayden, Janel; Sulo, Suela; Silver, Marc A

    2015-04-01

    Endothelial dysfunction has been recognized as a pathophysiologic mechanism in the progression of heart failure (HF). However, little attention has been given to the ability of dietary approaches to improve endothelial function. This study examined the effects of the Dietary Approaches to Stop Hypertension (DASH) diet on endothelial function, exercise capacity, and quality of life in patients with chronic symptomatic (stage C) HF. Forty-eight patients were randomized to follow the DASH diet (n = 24) or the general HF dietary recommendations (n = 24). Endothelial function was assessed by measuring large and small arterial elasticity (LAE and SAE) at rest. Exercise capacity (measured with the 6-minute walk test) and quality of life (measured with the Minnesota Living with Heart Failure Questionnaire) at baseline and 3 months were also evaluated. Patients were older adults with an average HF duration of 5 years. LAE at 1 month improved significantly in the DASH diet group (P DASH group had better exercise capacity (292 m vs 197 m; P = 0.018) and quality of life scores (21 vs 39; P = 0.006) over time, while sodium intake levels at 1, 2, and 3 months were comparable between the groups. Adhering to the DASH diet improved arterial compliance initially and improved exercise capacity and quality of life scores at 3 months. The DASH diet may be an important adjunctive therapy for patients with symptomatic HF.

  15. 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.

  16. Growth hormone therapy influences endothelial function in children with renal failure.

    NARCIS (Netherlands)

    Lilien, M.R.; Schröder, C.H.; Levtchenko, E.N.; Koomans, H.A.

    2004-01-01

    Endothelial dysfunction, an early step in atherogenesis, is prevalent in children with renal insufficiency. Endothelial dysfunction in growth hormone deficiency is reversed by growth hormone (rhGH) therapy. Renal failure induces growth hormone resistance at the receptor and post-receptor level,

  17. Lenalidomide, an anti-tumor drug, regulates retinal endothelial cell function: Implication for treating ocular neovascular disorder

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    Dong, Ling-Feng; Yao, Jin; Wang, Xiao-Qun; Shan, Kun; Yang, Hong [Eye Hospital, Nanjing Medical University, Nanjing (China); The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing (China); Yan, Biao, E-mail: yanbiao1982@hotmail.com [Eye Hospital, Nanjing Medical University, Nanjing (China); The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing (China); Jiang, Qin, E-mail: jiangqin710@126.com [Eye Hospital, Nanjing Medical University, Nanjing (China); The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing (China)

    2015-10-02

    Ocular angiogenesis is an important pathologic character of several ocular diseases, such as retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration (AMD). Inhibition of ocular angiogenesis has great therapeutic value for treating these dieses. Here we show that lenalidomide, an anti-tumor drug, has great anti-angiogenic potential in ocular diseases. Lenalidomide inhibits retinal endothelial cell viability in normal and pathological condition, and inhibits VEGF-induced endothelial cell migration and tube formation in vitro. Moreover, lenalidomide inhibits ocular angiogenesis in vivo through the reduction of angiogenesis- and inflammation-related protein expression. Collectively, lenalidomide is a promising drug for treating ocular angiogenesis through its anti-proliferative and anti-inflammatory property. - Highlights: • Lenalidomide inhibits retinal endothelial cell viability in vitro. • Lenalidomide inhibits retinal endothelial cell migration and tube formation. • Lenalidomide inhibits pathological ocular angiogenesis in vivo. • Lenalidomide inhibits angiogenesis- and inflammation-related protein expression.

  18. Lenalidomide, an anti-tumor drug, regulates retinal endothelial cell function: Implication for treating ocular neovascular disorder

    International Nuclear Information System (INIS)

    Dong, Ling-Feng; Yao, Jin; Wang, Xiao-Qun; Shan, Kun; Yang, Hong; Yan, Biao; Jiang, Qin

    2015-01-01

    Ocular angiogenesis is an important pathologic character of several ocular diseases, such as retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration (AMD). Inhibition of ocular angiogenesis has great therapeutic value for treating these dieses. Here we show that lenalidomide, an anti-tumor drug, has great anti-angiogenic potential in ocular diseases. Lenalidomide inhibits retinal endothelial cell viability in normal and pathological condition, and inhibits VEGF-induced endothelial cell migration and tube formation in vitro. Moreover, lenalidomide inhibits ocular angiogenesis in vivo through the reduction of angiogenesis- and inflammation-related protein expression. Collectively, lenalidomide is a promising drug for treating ocular angiogenesis through its anti-proliferative and anti-inflammatory property. - Highlights: • Lenalidomide inhibits retinal endothelial cell viability in vitro. • Lenalidomide inhibits retinal endothelial cell migration and tube formation. • Lenalidomide inhibits pathological ocular angiogenesis in vivo. • Lenalidomide inhibits angiogenesis- and inflammation-related protein expression.

  19. Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2) Functions to Promote Uterine Decidual Angiogenesis during Early Pregnancy in the Mouse

    Science.gov (United States)

    Douglas, Nataki C.; Tang, Hongyan; Gomez, Raul; Pytowski, Bronislaw; Hicklin, Daniel J.; Sauer, Christopher M.; Kitajewski, Jan; Sauer, Mark V.; Zimmermann, Ralf C.

    2009-01-01

    Implantation of an embryo induces rapid proliferation and differentiation of uterine stromal cells, forming a new structure, the decidua. One salient feature of decidua formation is a marked increase in maternal angiogenesis. Vascular endothelial growth factor (VEGF)-dependent pathways are active in the ovary, uterus, and embryo, and inactivation of VEGF function in any of these structures might prevent normal pregnancy development. We hypothesized that decidual angiogenesis is regulated by VEGF acting through specific VEGF receptors (VEGFRs). To test this hypothesis, we developed a murine pregnancy model in which systemic administration of a receptor-blocking antibody would act specifically on uterine angiogenesis and not on ovarian or embryonic angiogenesis. In our model, ovarian function was replaced with exogenous progesterone, and blocking antibodies were administered prior to embryonic expression of VEGFRs. After administration of a single dose of the anti-VEGFR-2 antibody during the peri-implantation period, no embryos were detected on embryonic d 10.5. The pregnancy was disrupted because of a significant reduction in decidual angiogenesis, which under physiological conditions peaks on embryonic d 5.5 and 6.5. Inactivation of VEGFR-3 reduced angiogenesis in the primary decidual zone, whereas administration of VEGFR-1 blocking antibodies had no effect. Pregnancy was not disrupted after administration of anti-VEGFR-3 or anti-VEGFR-1 antibodies. Thus, the VEGF/VEGFR-2 pathway plays a key role in the maintenance of early pregnancy through its regulation of peri-implantation angiogenesis in the uterine decidua. This newly formed decidual vasculature serves as the first exchange apparatus for the developing embryo until the placenta becomes functionally active. PMID:19406950

  20. Adhesion molecule expression and function of primary endothelial cells in benign and malignant tissues correlates with proliferation.

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    Wolfgang Sievert

    Full Text Available BACKGROUND: Comparative analysis of the cellular biology of the microvasculature in different tissues requires the availability of viable primary endothelial cells (ECs. This study describes a novel method to isolate primary ECs from healthy organs, repair blastemas and tumors as examples of non-proliferating and proliferating benign and malignant tissues and their functional characterization. METHODOLOGY/PRINCIPAL FINDINGS: Single cell suspensions from hearts, lungs, repair blastemas and tumors were incubated consecutively with an anti-CD31 antibody and magnetic micro-beads, coupled to a derivative of biotin and streptavidin, respectively. Following magnetic bead separation, CD31-positive ECs were released by biotin-streptavidin competition. In the absence of micro-beads, ECs became adherent to plastic surfaces. ECs from proliferating repair blastemas and tumors were larger and exhibited higher expression densities of CD31, CD105 and CD102 compared to those from non-proliferating normal tissues such as heart and lung. The expression density of CD34 was particularly high in tumor-derived ECs, and that of CD54 and CD144 in ECs of repair blastemas. Functionally, ECs of non-proliferating and proliferating tissues differed in their capacity to form tubes in matrigel and to align under flow conditions. CONCLUSIONS/SIGNIFICANCE: This method provides a powerful tool to generate high yields of viable, primary ECs of different origins. The results suggest that an altered expression of adhesion molecules on ECs in proliferating tissues contribute to loss of EC function that might cause a chaotic tumor vasculature.

  1. Functional neuroimaging of normal aging: Declining brain, adapting brain.

    Science.gov (United States)

    Sugiura, Motoaki

    2016-09-01

    Early functional neuroimaging research on normal aging brain has been dominated by the interest in cognitive decline. In this framework the age-related compensatory recruitment of prefrontal cortex, in terms of executive system or reduced lateralization, has been established. Further details on these compensatory mechanisms and the findings reflecting cognitive decline, however, remain the matter of intensive investigations. Studies in another framework where age-related neural alteration is considered adaptation to the environmental change are recently burgeoning and appear largely categorized into three domains. The age-related increase in activation of the sensorimotor network may reflect the alteration of the peripheral sensorimotor systems. The increased susceptibility of the network for the mental-state inference to the socioemotional significance may be explained by the age-related motivational shift due to the altered social perception. The age-related change in activation of the self-referential network may be relevant to the focused positive self-concept of elderly driven by a similar motivational shift. Across the domains, the concept of the self and internal model may provide the theoretical bases of this adaptation framework. These two frameworks complement each other to provide a comprehensive view of the normal aging brain. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Haroldo A Toque

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

  4. Early captopril treatment inhibits DNA synthesis in endothelial cells and normalization of maximal coronary flow in infarcted rat hearts

    NARCIS (Netherlands)

    Nelissen-Vrancken, H. J.; Kuizinga, M. C.; Daemen, M. J.; Smits, J. F.

    1998-01-01

    Cardiac remodeling due to myocardial infarction (MI) includes myocyte hypertrophy, collagen deposition, a rise in DNA synthesis, and normalization of initially diminished maximal coronary bloodflow. Previously, we demonstrated that early captopril treatment can prevent the rise in total DNA

  5. High Endothelial Venules and Other Blood Vessels: Critical Regulators of Lymphoid Organ Development and Function

    Science.gov (United States)

    Ager, Ann

    2017-01-01

    The blood vasculature regulates both the development and function of secondary lymphoid organs by providing a portal for entry of hemopoietic cells. During the development of lymphoid organs in the embryo, blood vessels deliver lymphoid tissue inducer cells that initiate and sustain the development of lymphoid tissues. In adults, the blood vessels are structurally distinct from those in other organs due to the requirement for high levels of lymphocyte recruitment under non-inflammatory conditions. In lymph nodes (LNs) and Peyer’s patches, high endothelial venules (HEVs) especially adapted for lymphocyte trafficking form a spatially organized network of blood vessels, which controls both the type of lymphocyte and the site of entry into lymphoid tissues. Uniquely, HEVs express vascular addressins that regulate lymphocyte entry into lymphoid organs and are, therefore, critical to the function of lymphoid organs. Recent studies have demonstrated important roles for CD11c+ dendritic cells in the induction, as well as the maintenance, of vascular addressin expression and, therefore, the function of HEVs. Tertiary lymphoid organs (TLOs) are HEV containing LN-like structures that develop inside organized tissues undergoing chronic immune-mediated inflammation. In autoimmune lesions, the development of TLOs is thought to exacerbate disease. In cancerous tissues, the development of HEVs and TLOs is associated with improved patient outcomes in several cancers. Therefore, it is important to understand what drives the development of HEVs and TLOs and how these structures contribute to pathology. In several human diseases and experimental animal models of chronic inflammation, there are some similarities between the development and function of HEVs within LN and TLOs. This review will summarize current knowledge of how hemopoietic cells with lymphoid tissue-inducing, HEV-inducing, and HEV-maintaining properties are recruited from the bloodstream to induce the development and

  6. 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.

  7. Osteoblastic and Vascular Endothelial Niches, Their Control on Normal Hematopoietic Stem Cells, and Their Consequences on the Development of Leukemia

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    Bella S. Guerrouahen

    2011-01-01

    Full Text Available Stem cell self-renewal is regulated by intrinsic mechanisms and extrinsic signals mediated via specialized microenvironments called “niches.” The best-characterized stem cell is the hematopoietic stem cell (HSC. Self-renewal and differentiation ability of HSC are regulated by two major elements: endosteal and vascular regulatory elements. The osteoblastic niche localized at the inner surface of the bone cavity might serve as a reservoir for long-term HSC storage in a quiescent state. Whereas the vascular niche, which consists of sinusoidal endothelial cell lining blood vessel, provides an environment for short-term HSC proliferation and differentiation. Both niches act together to maintain hematopoietic homeostasis. In this paper, we provide some principles applying to the hematopoietic niches, which will be useful in the study and understanding of other stem cell niches. We will discuss altered microenvironment signaling leading to myeloid lineage disease. And finally, we will review some data on the development of acute myeloid leukemia from a subpopulation called leukemia-initiating cells (LIC, and we will discuss on the emerging evidences supporting the influence of the microenvironment on chemotherapy resistance.

  8. The relationships between visit-to-visit blood pressure variability and renal and endothelial function in chronic kidney disease.

    Science.gov (United States)

    Nakano, Chikara; Morimoto, Satoshi; Nakahigashi, Mitsutaka; Kusabe, Makiko; Ueda, Hiroko; Someya, Kazunori; Ichihara, Atsuhiro; Iwasaka, Toshiji; Shiojima, Ichiro

    2015-03-01

    Visit-to-visit blood pressure variability has been shown to be an independent risk factor for cardiovascular diseases. High visit-to-visit blood pressure variability and endothelial dysfunction are observed in patients with chronic kidney disease. It is therefore assumed that high variability in visit-to-visit blood pressure measurements may be associated with endothelial dysfunction in these patients. The present study investigated the associations between visit-to-visit blood pressure variability and renal and endothelial function in patients with chronic kidney disease. We analyzed 150 consecutive patients with predialysis chronic kidney disease who visited our outpatient clinic from January 2006 to December 2010. The study examined the relationships between variability in visit-to-visit systolic blood pressure levels or mean systolic blood pressure (M SBP) and estimated glomerular filtration rate (eGFR) and flow-mediated dilation, an index of endothelial function. Variability in visit-to-visit systolic blood pressure showed a significant negative association with eGFR, independent of age, hemoglobin A1c, low-density lipoprotein (LDL) cholesterol and uric acid, whereas M SBP did not. Similarly, variability in SBP showed a significant negative association with flow-mediated dilation, independent of age, eGFR, HbA1c, LDL cholesterol and M SBP. These data indicate that variability in visit-to-visit blood pressure measurements is associated with impaired renal and endothelial function in patients with chronic kidney disease. This finding suggests that reducing blood pressure fluctuations might have beneficial effects in patients with chronic kidney disease, although this point needs to be addressed by future studies.

  9. The effects of physical training on cardiovascular parameters, lipid disorders and endothelial function

    Directory of Open Access Journals (Sweden)

    Ranković Goran

    2012-01-01

    Full Text Available Bacground/Aim. Regular physical activity is widely accepted as factor that reduces all-cause mortality and improves a number of health outcomes. The aim of this study was to investigate the effects of aerobic exercise training on cardiovascular parameters, lipid profile and endothelial function in patients with stable coronary artery disease (CAD. Methods. The study included seventy patients with stable CAD. All the patients were divided into two groups: the group I - 33 patients with CAD and with regular aerobic physical training during cardiovascular rehabilitation program phase II for 3 weeks in our rehabilitation center and 3 weeks after that in their home setting, and the group II (control - 37 patients with CAD and sedentary lifestyle. Exercise training consisted of continual aerobic exercise for 45 minutes on a treadmill, room bicycle or walking, three times a week. We determined lipid and cardiovascular parameters and nitric oxide (NO concentration at the beginning and after a six-week of training. Results. There were no significant differences in body weight, waist circumference and waist/hip ratio at the start and at the end of physical training program. Physical training significantly reduced body mass index after six weeks compared to the initial and control values. Physical training significantly reduced systolic and diastolic blood pressure and heart rate after a six-week training period (p < 0.05. Heart rate was significantly lower after a training period as compared to the control (p < 0.05. A significant reduction of triglyceride and increased high density lipoprotein cholesterol (HDL-C concentration after cardiovascular rehabilitation were registered (p < 0.05. The concentration of triglycerides was significantly lower while NO and HDL-C were higher after six weeks in the exercise training group (p < 0.05. Conclusion. Dynamic training can improve blood pressure in patients with moderate to severe hypertension and reduce the

  10. Impact of introducer sheath coating on endothelial function in humans after transradial coronary procedures.

    Science.gov (United States)

    Dawson, Ellen A; Rathore, Sudhir; Cable, N Timothy; Wright, D Jay; Morris, John L; Green, Daniel J

    2010-04-01

    The aim of this study was to compare the impact of transradial catheterization with hydrophilic-coated catheter sheaths versus uncoated sheaths on NO-mediated endothelial-dependent and -independent vasodilator function. Thirty-five subjects undergoing transradial catheterization were recruited and assessed before and the day after catheterization. A subgroup was also assessed 3 to 4 months after catheterization. Subjects received hydrophilic-coated sheaths (n=15) or uncoated sheaths (n=20). Radial artery flow-mediated dilatation and endothelium- and NO-dependent arterial dilatation were assessed within the region of sheath placement. Glyceryl trinitrate endothelium-independent NO-mediated function was also assessed. The noncatheterized arm provided an internal control. Flow-mediated dilatation in the catheterized arm decreased from 10.3+/-3.8% to 5.3+/-3.3% and 8.1+/-2.4% to 5.2+/-3.7% in the coated and uncoated groups, respectively (P<0.01). These values returned toward baseline levels approximately 3 months later (coated, 6.4+/-1.4%; uncoated, 9.4+/-4.1%; P<0.05) versus postprocedure. Glyceryl trinitrate decreased from 14.8+/-7.2% to 9.5+/-4.1% (P<0.05) in the coated group and from 12.2+/-4.6% to 7.5+/-4.2% (P<0.01) in the uncoated group. Values returned to baseline at approximately 3 months (coated, 16.6+/-5.6%; uncoated, 12.1+/-3.9%; P<0.05). There was no difference in the magnitude of decrease in flow-mediated dilatation or glyceryl trinitrate between coated and uncoated groups. No changes in function occurred in the noncatheterized arm. Placement of a catheter sheath inside the radial artery disrupts vasodilator function, which recovers after 3 months. No differences were evident between hydrophilic-coated and uncoated sheaths.

  11. [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.

  12. TNF signaling inhibition in the CNS: implications for normal brain function and neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    Tansey Malú G

    2008-10-01

    Full Text Available Abstract The role of tumor necrosis factor (TNF as an immune mediator has long been appreciated but its function in the brain is still unclear. TNF receptor 1 (TNFR1 is expressed in most cell types, and can be activated by binding of either soluble TNF (solTNF or transmembrane TNF (tmTNF, with a preference for solTNF; whereas TNFR2 is expressed primarily by microglia and endothelial cells and is preferentially activated by tmTNF. Elevation of solTNF is a hallmark of acute and chronic neuroinflammation as well as a number of neurodegenerative conditions including ischemic stroke, Alzheimer's (AD, Parkinson's (PD, amyotrophic lateral sclerosis (ALS, and multiple sclerosis (MS. The presence of this potent inflammatory factor at sites of injury implicates it as a mediator of neuronal damage and disease pathogenesis, making TNF an attractive target for therapeutic development to treat acute and chronic neurodegenerative conditions. However, new and old observations from animal models and clinical trials reviewed here suggest solTNF and tmTNF exert different functions under normal and pathological conditions in the CNS. A potential role for TNF in synaptic scaling and hippocampal neurogenesis demonstrated by recent studies suggest additional in-depth mechanistic studies are warranted to delineate the distinct functions of the two TNF ligands in different parts of the brain prior to large-scale development of anti-TNF therapies in the CNS. If inactivation of TNF-dependent inflammation in the brain is warranted by additional pre-clinical studies, selective targeting of TNFR1-mediated signaling while sparing TNFR2 activation may lessen adverse effects of anti-TNF therapies in the CNS.

  13. Impact of circulating esterified eicosanoids and other oxylipins on endothelial function

    Science.gov (United States)

    Eicosanoids including epoxyeicosatrienoic acids (EETs) and hydroxyeicosatetraenoic (HETEs) and other oxylipins derived from polyunsaturated fatty acids have emerging roles in endothelial inflammation and its atherosclerotic consequences. Unlike many eicosanoids, they are known to be esterified in c...

  14. Impaired endothelial function after aneurysmal subarachnoid haemorrhage correlates with arginine:asymmetric dimethylarginine ratio

    DEFF Research Database (Denmark)

    Bergström, A; Staalsø, J M; Romner, B

    2014-01-01

    BACKGROUND: Endothelial dysfunction might be involved in the development of cerebral vasospasm after aneurysmal subarachnoid haemorrhage (SAH). METHODS: This prospective observational study of 48 SAH subjects and 23 control subjects examined associations between reactive hyperaemia index (RHI...

  15. Eldecalcitol prevents endothelial dysfunction in postmenopausal osteoporosis model rats.

    Science.gov (United States)

    Serizawa, Kenichi; Yogo, Kenji; Tashiro, Yoshihito; Takeda, Satoshi; Kawasaki, Ryohei; Aizawa, Ken; Endo, Koichi

    2016-02-01

    Postmenopausal women have high incidence of cardiovascular events as estrogen deficiency can cause endothelial dysfunction. Vitamin D is reported to be beneficial on endothelial function, but it remains controversial whether vitamin D is effective for endothelial dysfunction under the treatment for osteoporosis in postmenopausal women. The aim of this study was to evaluate the endothelial protective effect of eldecalcitol (ELD) in ovariectomized (OVX) rats. ELD (20  ng/kg) was orally administrated five times a week for 4 weeks from 1 day after surgery. After that, flow-mediated dilation (FMD) as an indicator of endothelial function was measured by high-resolution ultrasound in the femoral artery of living rats. ELD ameliorated the reduction of FMD in OVX rats. ELD inhibited the increase in NOX4, nitrotyrosine, and p65 and the decrease in dimer/monomer ratio of nitric oxide synthase in OVX rat femoral arteries. ELD also prevented the decrease in peroxisome proliferator-activated receptor gamma (PPARγ) in femoral arteries and cultured endothelial cells. Although PPARγ is known to inhibit osteoblastogenesis, ELD understandably increased bone mineral density of OVX rats without increase in PPARγ in bone marrow. These results suggest that ELD prevented the deterioration of endothelial function under condition of preventing bone loss in OVX rats. This endothelial protective effect of ELD might be exerted through improvement of endothelial nitric oxide synthase uncoupling, which is mediated by an antioxidative effect through normalization of vascular PPARγ/NF-κB signaling. © 2016 Society for Endocrinology.

  16. Physiological adaptation of endothelial function to pregnancy: systematic review and meta-analysis.

    Science.gov (United States)

    Lopes van Balen, V A; van Gansewinkel, T A G; de Haas, S; van Kuijk, S M J; van Drongelen, J; Ghossein-Doha, C; Spaanderman, M E A

    2017-12-01

    To establish reference values for flow-mediated dilatation (FMD) and brachial artery diameter (BAD) in pregnancy and to provide insight into the physiological and pathological course of endothelial adaptation throughout human singleton pregnancy. A meta-analysis was performed following a systematic review of current literature on FMD, as a derivative for endothelial function, and BAD, throughout uncomplicated and complicated pregnancy. PubMed (NCBI) and EMBASE (Ovid) electronic databases were used for the literature search, which was performed from inception to 9 June 2016. To allow judgment of changes in comparison with the non-pregnant state, studies were required to report both non-pregnant mean reference of FMD (matched control group, prepregnancy or postpartum measurement) and mean FMD at a predetermined and reported gestational age. Pooled mean differences between the reference and pregnant FMD values were calculated for predefined intervals of gestational age. Fourteen studies that enrolled 1231 participants met the inclusion criteria. Publication dates ranged from 1999 to 2014. In uncomplicated pregnancy, FMD was increased in the second and third trimesters. Between 15 and 21 weeks of gestation, absolute FMD increased the most, by a mean (95% CI) of 1.89% (0.25-3.53%). This was a relative increase of 22.5% (3.0-42.0%) compared with the non-pregnant reference. BAD increased progressively, in a steady manner, by the second trimester but not significantly in the first half of the second trimester. We could not discern differences in FMD and BAD between complicated and uncomplicated pregnancies at 29-35 weeks' gestation, reported in the three studies that met our inclusion criteria. Despite the increase in FMD and BAD throughout gestation, both reference curves were characterized by wide 95% CIs. During healthy pregnancy, endothelium-dependent vasodilatation and BAD increase. Women with a complicated pregnancy had FMD values within the lower range when

  17. Influence of heavy ions on cell survival, cytogenetic damage and mitochondrial function of human endothelial cells

    Science.gov (United States)

    Ritter, Sylvia; Helm, Alexander; Lee, Ryonfa; Pollet, Dieter; Durante, Marco

    There is increasing evidence that there is an elevated risk of cardiovascular disease among atomic bomb survivors and radiotherapy patients, typically developing with a long latency. However, essentially no information is available on the potential cardiovascular risks associated with space radiation, in particular heavy ions. To address this issue, we have chosen human umbilical vein endothelial cells (HUVEC) as a model system. Cells at an early passage number were irradiated with 0.1 to 4 Gy of either 9.8 MeV/u C-ions (LET=170 keV/µm), 91 MeV/u C-ions (LET=29 keV/µm) or 250 kV X-rays. Cells were regularly subcultured up to 40 days (20 population doublings) post-irradiation. Immediately after exposure cell inactivation was deter-mined by the colony forming assay. Furthermore, at selected time-points cytogenetic damage (formation of micronuclei in binucleated cells) and the mitochondrial membrane potential ΨM (flow cytometric analysis following JC-1 staining) were assessed. Measurement of the directly induced radiation damage showed that 9.8 MeV/u and 91 MeV/u C-ions were more effective than X-rays (i.e. about 3 and 2 times, respectively) with respect to cell inactivation or the in-duction of cytogenetic damage. At the subsequent days in the irradiated cultures the number of cells with micronuclei declined to the control level (3-5Altogether our data indicate that under the applied radiation conditions the integrity of mitochondria which play a significant role in the regulation of cardiovascular cell function is not impaired. With respect to directly induced genetic damage C-ions are more effective than X-rays as observed in other cell systems. If the effectiveness of charged particles for the occurrence of late chromosomal damage in endothelial cells is higher than that of sparsely ionizing radiation needs further clarification. The data obtained up to now indicate that sophisticated cytogenetic techniques have to be applied in order to draw any firm

  18. Occurring of In Vitro Functional Vasculogenic Pericytes from Human Circulating Early Endothelial Precursor Cell Culture

    Directory of Open Access Journals (Sweden)

    Silvia Cantoni

    2015-01-01

    Full Text Available Pericytes are periendothelial cells of the microcirculation which contribute to tissue homeostasis and hemostasis by regulating microvascular morphogenesis and stability. Because of their multipotential ex vivo differentiation capabilities, pericytes are becoming very interesting in regenerative medicine field. Several studies address this issue by attempting to isolate pericyte/mesenchymal-like cells from peripheral blood; however the origin of these cells and their culture conditions are still debated. Here we showed that early Endothelial Progenitor Cells (EPCs expressing CD45+/CD146+/CD31+ can be a source of cells with pericyte/mesenchymal phenotype and function, identified as human Progenitor Perivascular Cells (hPPCs. We provided evidence that hPPCs have an immunophenotype consistent with Mesenchymal Stem Cells (MSCs from human adipose tissue (hASCs and fetal membranes of term placenta (FM-hMSCs. In addition, hPPCs can be subcultured and exhibit expression of pluripotent genes (OCT-4, KLF-4, and NANOG as well as a remarkable vasculogenic potential. Our findings could be helpful to develop innovative cell-based therapies for future clinical applications with distinct therapeutic purposes.

  19. 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

    amplitude tonometry technology in acute stroke patients. Similarly, reliability was tested in healthy subjects devoid of vascular disease to estimate reactivity and reliability in a younger non-stroke population. MATERIALS AND METHODS: EF was assessed using the EndoPAT2000 in 20 healthy volunteers (men 50......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...

  20. Nitric oxide and superoxide dismutase modulate endothelial progenitor cell function in type 2 diabetes mellitus

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    Brenner Benjamin

    2009-10-01

    Full Text Available Abstract Background The function of endothelial progenitor cells (EPCs, which are key cells in vascular repair, is impaired in diabetes mellitus. Nitric oxide (NO and reactive oxygen species can regulate EPC functions. EPCs tolerate oxidative stress by upregulating superoxide dismutase (SOD, the enzyme that neutralizes superoxide anion (O2-. Therefore, we investigated the roles of NO and SOD in glucose-stressed EPCs. Methods The functions of circulating EPCs from patients with type 2 diabetes were compared to those from healthy individuals. Healthy EPCs were glucose-stressed, and then treated with insulin and/or SOD. We assessed O2- generation, NO production, SOD activity, and their ability to form colonies. Results EPCs from diabetic patients generated more O2-, had higher NAD(PH oxidase and SOD activity, but lower NO bioavailability, and expressed higher mRNA and protein levels of p22-phox, and manganese SOD and copper/zinc SOD than those from the healthy individuals. Plasma glucose and HbA1c levels in the diabetic patients were correlated negatively with the NO production from their EPCs. SOD treatment of glucose-stressed EPCs attenuated O2- generation, restored NO production, and partially restored their ability to form colonies. Insulin treatment of glucose-stressed EPCs increased NO production, but did not change O2- generation and their ability to form colonies. However, their ability to produce NO and to form colonies was fully restored after combined SOD and insulin treatment. Conclusion Our data provide evidence that SOD may play an essential role in EPCs, and emphasize the important role of antioxidant therapy in type 2 diabetic patients.

  1. High Endothelial Venules and Lymphatic Vessels in Tertiary Lymphoid Organs: Characteristics, Functions, and Regulation

    Directory of Open Access Journals (Sweden)

    Nancy H Ruddle

    2016-11-01

    Full Text Available High endothelial venules (HEVs and lymphatic vessels (LVs are essential for the function of the immune system, by providing communication between the body and lymph nodes (LNs, specialized sites of antigen presentation and recognition. HEVs bring in naïve and central memory cells and LVs transport antigen, antigen presenting cells, and lymphocytes in and out of LNs. Tertiary lymphoid organs (TLOs are accumulations of lymphoid and stromal cells that arise and organize at ectopic sites in response to chronic inflammation in autoimmunity, microbial infection, graft rejection, and cancer. TLOs are distinguished from primary lymphoid organs-the thymus and bone marrow, and secondary lymphoid organs (SLOs-the LNs, spleen, and Peyer’s patches, in that they arise in response to inflammatory signals, rather than in ontogeny. TLOs usually do not have a capsule, but are rather contained within the confines of another organ. Their structure, cellular composition, chemokine expression, and vascular and stromal support resemble SLOs and are the defining aspects of TLOs. T and B cells, antigen presenting cells, fibroblast reticular cells and other stromal cells and vascular elements including HEVs and LVs are all typical components of TLOS. A key question is whether the HEVs and LVs play comparable roles and are regulated similarly to those in LNs. Data are presented that support this concept, especially with regard to TLO HEVs. Emerging data suggest that the functions and regulation of TLO LVs are also similar to those in LNs. These observations support the concept that TLOs are not merely cellular accumulations, but are functional entities that provide sites to generate effector cells, and that their HEVs and LVs are crucial elements in those activities.

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

    Science.gov (United States)

    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.

  3. Relationship of hyperglycemia with endothelial function, renal function, lipidemic profile, and morphological changes of blood cells in patients with insufficient compensation of type 2 diabetes mellitus with hypertension

    Directory of Open Access Journals (Sweden)

    N. O. Pertseva

    2014-12-01

    Full Text Available Many questions about the relationship between endothelial dysfunction and morphological substrate of hemostasis damage that occur during the progress of type 2 diabetes mellitus and arterial hypertension require clarification and further advance. In 87 patients with insufficient glycemic compensation using clinical, laboratory, morphological methods and correlational analysis were identified association between endothelial dysfunction, degree of renal function damage, lipidemic profile and morphological changes of vascular-platelet hemostasis. It has been established that in the insufficient glycemic control by a significant strengthening relationships between indicators of endothelial dysfunction and damaged platelet hemostasis (up to r=+0.95 formed significant correlations of ultrastructural characteristics of platelets with clinical and laboratory signs of nephropathic and dyslipidemic changes.

  4. Characteristic functions of scale mixtures of multivariate skew-normal distributions

    KAUST Repository

    Kim, Hyoung-Moon

    2011-08-01

    We obtain the characteristic function of scale mixtures of skew-normal distributions both in the univariate and multivariate cases. The derivation uses the simple stochastic relationship between skew-normal distributions and scale mixtures of skew-normal distributions. In particular, we describe the characteristic function of skew-normal, skew-t, and other related distributions. © 2011 Elsevier Inc.

  5. 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

    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...

  6. Insulin therapy improves insulin-stimulated endothelial function in patients with type 2 diabetes and ischemic heart disease

    DEFF Research Database (Denmark)

    Rask-Madsen, C; Ihlemann, N; Krarup, T

    2001-01-01

    Blunted insulin-stimulated endothelial function may be a mechanism for the development of atherothrombotic disease in type 2 diabetes, but it is unknown whether hypoglycemic drug therapy can modulate this abnormality. We studied patients with type 2 diabetes and stable ischemic heart disease (n......, and 69 +/- 36% (P = 0.0002). In the time control group, insulin stimulation remained without effect after 8 weeks (P = 0.7). In conclusion, insulin therapy partly restores insulin-stimulated endothelial function in patients with type 2 diabetes and ischemic heart disease....... after intrabrachial infusion of insulin. Patients were restudied after 2 months of insulin therapy with four daily subcutaneous injections (treatment group, n = 19) or without hypoglycemic drug therapy (time control group, n = 9). Insulin infusion raised venous serum insulin in the forearm to high...

  7. Peptides-Derived from Thai Rice Bran Improves Endothelial Function in 2K-1C Renovascular Hypertensive Rats

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    Orachorn Boonla

    2015-07-01

    Full Text Available In recent years, a number of studies have investigated complementary medical approaches to the treatment of hypertension using dietary supplements. Rice bran protein hydrolysates extracted from rice is a rich source of bioactive peptides. The present study aimed to investigate the vasorelaxation and antihypertensive effects of peptides-derived from rice bran protein hydrolysates (RBP in a rat model of two kidney-one clip (2K-1C renovascular hypertension. 2K-1C hypertension was induced in male Sprague-Dawley rats by placing a silver clip around the left renal artery, whereas sham-operated rats were served as controls. 2K-1C and sham-operated rats were intragastrically administered with RBP (50 mg kg−1 or 100 mg kg−1 or distilled water continuously for six weeks. We observed that RBP augmented endothelium-dependent vasorelaxation in all animals. Administration of RBP to 2K-1C rats significantly reduced blood pressure and decreased peripheral vascular resistance compared to the sham operated controls (p < 0.05. Restoration of normal endothelial function and blood pressure was associated with reduced plasma angiotensin converting enzyme (ACE, decreased superoxide formation, reduced plasma malondialdehyde and increased plasma nitrate/nitrite (p < 0.05. Up-regulation of eNOS protein and down-regulation of p47phox protein were found in 2K-1C hypertensive rats-treated with RBP. Our results suggest that RBP possesses antihypertensive properties which are mainly due to the inhibition of ACE, and its vasodilatory and antioxidant activity.

  8. Change in endothelial function state under the influence of antihypertensive therapy in patients with arterial hypertension and high cardiovascular risk

    Directory of Open Access Journals (Sweden)

    Turlyun T.S.

    2014-03-01

    Full Text Available The article analyzes the indicators characterizing endothelial function in patients of distinguished groups at the initial stage of the study (visit 1 and during the treatment (visit 2. At baseline levels of endothelin-1 in the blood of patients of all groups did not differ significantly between the groups distinguished. After treatment, the dynamics of the indicator in all groups was positive and statistically significant (p0,60.

  9. Impaired endothelial function in pediatric patients with turner syndrome and healthy controls: a case-control study

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    O'Gorman Clodagh S

    2012-04-01

    Full Text Available Abstract Background Turner Syndrome women are at high risk of vascular disease and the assessment of early risk factors in Turner Syndrome girls is an emerging focus of research. Our objective was to evaluate endothelial function (EF, a preclinical measure of atherosclerosis, in Turner Syndrome girls compared with controls. Methods A cross-sectional case-control study of Turner Syndrome girls and healthy controls. Subjects underwent fasting insulin and glucose with calculation of HOMA-IR, fasting lipid profile, anthropometrics, and EF testing using peripheral arterial tonometry (PAT. Subjects, aged 10-18 years, had karyotype-confirmed Turner Syndrome; growth hormone (GH, thyroxine and estrogen use were not exclusion criteria. Controls were age- and BMI-matched healthy girls. Fifteen Turner Syndrome and 15 controls were recruited. Results Turner Syndrome girls had lower height, higher HDL and higher waist:height ratio than controls. PAT-hyperemia ratio (RH-PAT scores were lower in Turner Syndrome (1.64 ± 0.34 vs. 2.08 ± 0.32, p = 0.002 indicating impaired EF. Among Turner Syndrome, RH-PAT did not vary with estrogen therapy or with karyotype 45,XO compared with other karyotypes. However, endothelial function was better in GH-treated compared with GH-untreated Turner Syndrome (1.80 ± 0.36 vs. 1.4 + 0.22, p = 0.02 although there were no differences in HOMA-IR, adiponectin or IGF-1. Conclusion Girls with Turner Syndrome exhibit impaired endothelial function compared with controls, which may explain higher risk for vascular disease. GH may protect endothelial function in Turner Syndrome.

  10. Effect of teriparatide treatment on endothelial function, glucose metabolism and inflammation markers in patients with postmenopausal osteoporosis.

    Science.gov (United States)

    Celer, Ozgen; Akalın, Aysen; Oztunali, Cigdem

    2016-10-01

    Teriparatide, an anabolic agent used in the treatment of postmenopausal osteoporosis, can induce effects similar to primary hyperparathyroidism. Our objective was to evaluate the effects of teriparatide on endothelial functions, glucose metabolism and inflammation markers in patients diagnosed with postmenopausal osteoporosis. This was a single-centre, single-arm, 6-month prospective study. Twenty-three postmenopausal women over 65 years old with a lumbar spine or femoral neck T-score of -4·0 or lower and having at least two compression fractures in thoracic or lumbar spine were studied. Low-dose intermittent teriparatide (20 μg/day) was supplemented with calcium carbonate (1000 mg elemental calcium) and 880 IU cholecalciferol for 6 months. The biochemical parameters for glucose metabolism, inflammation and atherosclerosis were determined. For the assessment of vascular endothelial function, carotid intima-media thickness (CIMT), brachial artery intima-media thickness (BIMT), per cent change in flow-mediated dilation (FMD%) and nitroglycerine-induced dilations (NID%) were measured on ultrasonography. The fasting plasma glucose, homoeostatic model assessment of insulin resistance, fibrinogen, homocysteine and high-density lipoprotein cholesterol increased significantly with teriparatide treatment (P teriparatide treatment (P > 0·05); however, FMD% and NID% showed significant decrease after treatment (P teriparatide treatment may adversely affect some parameters of glucose metabolism, inflammation and endothelial function. On the basis of our findings, further large-scale and controlled studies are needed to clarify the exact effect of teriparatide treatment on glucose metabolism, inflammation and endothelial function. © 2016 John Wiley & Sons Ltd.

  11. Effect of Chronic Social Stress on Endothelial Function of the Mesenteric Artery of Normotensive and Spontaneously Hypertensive Rats

    OpenAIRE

    Kaprinay B.; Bernatova I.; Sotnikova R.

    2016-01-01

    The aim of the work was to study the effect of chronic social stress induced by increased population density, “crowding stress” on blood pressure and endothelial function of arteries of male normotensive Wistar and spontaneously hypertensive (SHR) rats. Based on the results, we assume that social stress-induced reduction in endothelium-dependent relaxation and increased blood pressure of SHR rats is most likely associated with decreased bioavailability of nitric oxide.

  12. 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.

  13. Tpl2 Inhibitors Thwart Endothelial Cell Function in Angiogenesis and Peritoneal Dissemination

    Directory of Open Access Journals (Sweden)

    Wen-Jane Lee

    2013-09-01

    Full Text Available Angiogenesis is critical in the development of cancer, which involves several angiogenic factors in its peritoneal dissemination. The role of protein tumor progression locus 2 (Tpl2 in angiogenic factor-related endothelial cell angiogenesis is still unclear. To understand the precise mechanism(s of Tpl2 inhibition in endothelial cells, this study investigated the role of Tpl2 in mediating angiogenic signals using in vitro, in vivo, and ex vivo models. Results showed that inhibition of Tpl2 inhibitor significantly reduced peritoneal dissemination in a mouse model by positron emission tomography/computed tomography imaging. Simultaneously, inhibiting Tpl2 blocked angiogenesis in tumor nodules and prevented angiogenic factor-induced proliferating cell nuclear antigen (PCNA in endothelial cells. Vascular endothelial growth factor (VEGF or chemokine (C-X-C motif ligand 1 (CXCL1 increased Tpl2 kinase activity and phosphorylation in a dose- and time-dependent manner. Furthermore, Tpl2 inhibition or ablation by siRNA prevented the angiogenic signal-induced tube formation in Matrigel plug assay or aortic ring assay. Inhibiting Tpl2 also prevented the angiogenic factor-induced chemotactic motility and migration of endothelial cells. Tpl2 inhibition by CXCL1 or epidermal growth factor in endothelial cells was associated with inactivation of CCAAT/enhancer binding protein β, nuclear factor κ light-chain enhancer of activated B cells, and activating protein 1 and suppression of VEGF expression. Thus, Tpl2 inhibitors thwart Tpl2-regulated VEGF by inactivating transcription factors involved in angiogenic factor-triggered endothelial cell angiogenesis. These results suggest that the therapeutic inhibition of Tpl2 may extend beyond cancer and include the treatment of other diseases involving pathologic angiogenesis.

  14. The molecular mechanism for effects of TiN coating on NiTi alloy on endothelial cell function.

    Science.gov (United States)

    Yang, Dayun; Lü, Xiaoying; Hong, Ying; Xi, Tingfei; Zhang, Deyuan

    2014-08-01

    The aim of this study is to systematically investigate the molecular mechanism of different effects of nickel titanium (NiTi) alloy surface and titanium nitride (TiN) coating on endothelial cell function. Release of nickel (Ni) ion from bare and TiN-coated NiTi alloys and proliferation of endothelial cells on the two materials were evaluated, and then influence of the two materials on cellular protein expression profiles was investigated by proteomic technology. Subsequently, proteomic data were analyzed with bioinformatics analyses and further validated using a series of biological experiments. Results showed that although the two materials did not affect cell proliferation, the Ni ions released from bare NiTi alloy generated inhibition on pathways associated with actin cytoskeleton, focal adhesion, energy metabolism, inflammation, and amino acid metabolism. In comparison, TiN coating not only effectively prevented release of Ni ions from NiTi alloy, but also promoted actin cytoskeleton and focal adhesion formation, increased energy metabolism, enhanced regulation of inflammation, and promoted amino acid metabolism. Furthermore, the two processes, "the initial mediation of adsorbed serum protein layer to endothelial cell adhesion and growth on the two materials" from our previous study, and "the following action of the two materials on cellular protein expression profile", were linked up and comprehensively analyzed. It was found that in stage of cell adhesion (within 4 h), release of Ni ions from bare NiTi alloy was very low, and the activation of adsorbed proteins to cell adhesion and growth related biological pathways (such as regulation of actin cytoskeleton, and focal adhesion pathways) was almost as same as TiN-coated NiTi alloy. This indicated that the released Ni ions did not affect the mediation of adsorbed proteins to endothelial cell adhesion. However, in stage of cell growth and proliferation, the release of Ni ions from bare NiTi alloy increased with

  15. 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.)

  16. Novel Form of Curcumin Improves Endothelial Function in Young, Healthy Individuals: A Double-Blind Placebo Controlled Study

    Directory of Open Access Journals (Sweden)

    Jonathan M. Oliver

    2016-01-01

    Full Text Available Curcumin, a turmeric extract, may protect against cardiovascular diseases by enhancing endothelial function. In this randomized controlled double-blind parallel prospective study, fifty-nine healthy adults were assigned to placebo, 50 mg (50 mg, or 200 mg (200 mg curcumin, for 8 weeks. The higher curcumin (200 mg supplementation produced a dose-mediated improvement in endothelial function measured by flow-mediated dilation (FMD. The outcome was a clinically substantial 3.0% increase (90% CI 0.7 to 5.3%, p=0.032; benefit : harm odds ratio 546 : 1 with the 200 mg dose, relative to placebo. The 50 mg dose also increased FMD relative to placebo by 1.7% (−0.6 to 4.0%, p=0.23; 25 : 1, but the outcome was not clinically decisive. In apparently healthy adults, 8 weeks of 200 mg oral curcumin supplementation resulted in a clinically meaningful improvement in endothelial function as measured by FMD. Oral curcumin supplementation may present a simple lifestyle strategy for decreasing the risk of cardiovascular diseases. This trial was registered at ISRCTN registry (ISRCTN90184217.

  17. 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.)

  18. A microscopic view on the renal endothelial glycocalyx.

    Science.gov (United States)

    Dane, Martijn J C; van den Berg, Bernard M; Lee, Dae Hyun; Boels, Margien G S; Tiemeier, Gesa L; Avramut, M Cristina; van Zonneveld, Anton Jan; van der Vlag, Johan; Vink, Hans; Rabelink, Ton J

    2015-05-01

    Endothelial cells perform key homeostatic functions such as regulating blood flow, permeability, and aiding immune surveillance for pathogens. While endothelial activation serves normal physiological adaptation, maladaptation of these endothelial functions has been identified as an important effector mechanism in the progression of renal disease as well as the associated development of cardiovascular disease. The primary interface between blood and the endothelium is the glycocalyx. This carbohydrate-rich gel-like structure with its associated proteins mediates most of the regulatory functions of the endothelium. Because the endothelial glycocalyx is a highly dynamic and fragile structure ex vivo, and traditional tissue processing for staining and perfusion-fixation usually results in a partial or complete loss of the glycocalyx, studying its dimensions and function has proven to be challenging. In this review, we will outline the core functions of the glycocalyx and focus on different techniques to study structure-function relationships in kidney and vasculature. Copyright © 2015 the American Physiological Society.

  19. Effects of high glucose on human cavernous endothelial cells.

    Science.gov (United States)

    Ning, Hongxiu; Qiu, Xuefeng; Baine, Lia; Lin, Guiting; Lue, Tom F; Lin, Ching-Shwun

    2012-11-01

    To obtain experimental evidence for a causal effect of high glucose (HG) on cavernous endothelial dysfunction. Cavernous tissues were obtained from patients undergoing surgery for penile prosthesis implantation. Endothelial cells were isolated by binding to anti-CD31 antibody, followed by magnetic capture. Their endothelial identity was verified by flow cytometry and immunofluorescence staining for endothelial markers CD31, von Willebrand factor, and endothelial nitric oxide synthase, and by their ability to form tube-like structures in matrigel (tube formation) and to endocytose acetylated low-density lipoprotein (low-density lipoprotein uptake). The cells were then cultured under normal glucose (NG) (5 mM) or HG (25 mM) conditions, followed by analysis for endothelial gene expression, function, proliferation, apoptosis, and mitochondrial fragmentation. Human cavernous endothelial cell (HCEC) strains were established and determined to be nearly 100% pure endothelial cells. In the HG culture condition, HCECs expressed approximately 50% less CD31, von Willebrand factor, and endothelial nitric oxide synthase, but nearly twice as much collagen IV compared with HCECs grown in NG medium. HG also suppressed low-density lipoprotein uptake and tube formation by approximately 50%. HCECs grew significantly slower in the high-glucose medium than in the NG medium. Approximately 3 times as many cells exhibited apoptosis in the HG medium as in the NG medium. Approximately 4 times as many cells contained fragmented mitochondria in the HG medium as in the NG medium. HG caused a decrease in endothelial proliferation, function, and marker expression. It also caused an increase in endothelial collagen IV expression, apoptosis, and mitochondrial fragmentation. Together, these HG-induced changes in cavernous endothelial cells provide an explanation for hyperglycemia's detrimental effects on erectile function. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. 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

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

    Directory of Open Access Journals (Sweden)

    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

  2. Genetic engineering with endothelial nitric oxide synthase improves functional properties of endothelial progenitor cells from patients with coronary artery disease: an in vitro study.

    Science.gov (United States)

    Kaur, Savneet; Kumar, T R Santhosh; Uruno, Akira; Sugawara, Akira; Jayakumar, Karunakaran; Kartha, Chandrasekharan Cheranellore

    2009-11-01

    Recent studies have reported a marked impairment in the number and functions of endothelial progenitor cells (EPCs) in patients with coronary artery disease (CAD). In view of an important role of eNOS in angiogenesis, in the present study, we evaluated the effects of eNOS gene transfer in ex vivo expanded EPCs isolated from patients with CAD. The expanded EPCs were transfected with mammalian expression vector pcDNA3.1-eNOS containing the full-length human eNOS gene using lipofectamine. About 35-40% of the eNOS-EPCs had higher expression of eNOS as compared to untransfected EPCs. EPCs transfected with pcDNA3.0-EGFP, the plasmid vector expressing green fluorescent protein (GFP) were used as control. The untransfected, GFP-transfected and eNOS-transfected EPCs were compared in terms of important functional attributes of angiogenesis such as proliferation, migration, differentiation and adhesion/integration into tube-like structures in vitro. Functional studies revealed that in the presence of defined growth conditions, compared to the untransfected and GFP-transfected cells, eNOS-EPCs from patients with CAD have a significant increase in [3H] thymidine-labeled DNA (P < 0.01), migration (14.6 +/- 1.8 and 16.5 +/- 1.9 vs. 23.5 +/- 3.4 cells/field, P < 0.01), ability to differentiate into endothelial-like spindle-shaped cells (46 +/- 4.5 and 56.5 +/- 2.1 vs. 93.2 +/- 6.6 cells/field, P < 0.001) and also incorporation into tube-like structures on the matrigel (GFP-EPCs: 21.25 +/- 2.9 vs. GFP-eNOS-EPCs: 34.5 +/- 5.5 cells/field, P < 0.05). We conclude that eNOS gene transfection is a valuable approach to augment angiogenic properties of ex vivo expanded EPCs and eNOS-modified EPCs may offer significant advantages than EPCs alone in terms of their clinical use in patients with myocardial ischemia.

  3. Ubiquitination of basal VEGFR2 regulates signal transduction and endothelial function.

    Science.gov (United States)

    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.

  4. Expression and Function of the Homeostatic Molecule Del-1 in Endothelial Cells and the Periodontal Tissue

    Directory of Open Access Journals (Sweden)

    Jieun Shin

    2013-01-01

    Full Text Available Developmental endothelial locus-1 (Del-1 is an endothelial cell-secreted protein that limits the recruitment of neutrophils by antagonizing the interaction between the LFA-1 integrin on neutrophils and the intercellular adhesion molecule (ICAM-1 on endothelial cells. Mice with genetic or age-associated Del-1 deficiency exhibit increased neutrophil infiltration in the periodontium resulting in inflammatory bone loss. Here we investigated additional novel mechanisms whereby Del-1 could interfere with neutrophil recruitment and inflammation. Treatment of human endothelial cells with Del-1 did not affect the expression of endothelial molecules involved in the leukocyte adhesion cascade (ICAM-1, VCAM-1, and E-selectin. Moreover, genetic or age-associated Del-1 deficiency did not significantly alter the expression of these adhesion molecules in the murine periodontium, further ruling out altered adhesion molecule expression as a mechanism whereby Del-1 regulates leukocyte recruitment. Strikingly, Del-1 inhibited ICAM-1-dependent chemokine release (CXCL2, CCL3 by neutrophils. Therefore, Del-1 could potentially suppress the amplification of inflammatory cell recruitment mediated through chemokine release by infiltrating neutrophils. Interestingly, Del-1 was itself regulated by inflammatory stimuli, which generally exerted opposite effects on adhesion molecule expression. The reciprocal regulation between Del-1 and inflammation may contribute to optimally balance the protective and the potentially harmful effects of inflammatory cell recruitment.

  5. 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.

  6. Nilotinib Does Not Alter the Secretory Functions of Carotid Artery Endothelial Cells in a Prothrombotic or Antithrombotic Fashion.

    Science.gov (United States)

    Katgı, Abdullah; Sevindik, Ömür Gökmen; Gökbulut, Aysun Adan; Özsan, Güner Hayri; Yüksel, Faize; Solmaz, Şerife Medeni; Alacacıoğlu, İnci; Özcan, Mehmet Ali; Demirkan, Fatih; Baran, Yusuf; Pişkin, Özden

    2015-10-01

    There have been concerns about the possible prothrombotic effects of nilotinib, especially in patients having cardiovascular risk factors. The potential mechanism behind the increased risk of thromboembolic events is still not clear. In this study, we aimed to evaluate possible harmful effects of nilotinib on endothelial cells. To this aim, we examined proliferative capacity and secretory functions of healthy human carotid artery endothelial cells (HCtAECs) in response to nilotinib. 3-(4,5-Dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation method was used to determine antiproliferative effects of nilotinib on HCtAECs. The HCtAECs were incubated with 5, 10, and 100 nmol/L doses of nilotinib for 72 hours. Then, in order to assess the endothelial function, levels of nitric oxide (NO), von Willebrand factor (vWF), tissue plasminogen activator, plasminogen activator inhibitor 1 (PAI-1), and endothelin 1 (ET-1) were evaluated using enzyme-linked immunosorbent assay from tissue culture supernatants. There were slight but statistically significant decreases in cell proliferation in response to nilotinib. Nilotinib increased the secretion of t-PA, PAI-1, and vWF in a dose-dependent manner when compared with the untreated control group. The ET-1 secretion was lower in 5 nmol/L and higher in 10 and 100 nmol/L nilotinib-treated cells as compared to untreated cells. Regarding NO secretion, lower levels were observed in 5 and 10 nmol/L, and higher levels were detected in 100 nmol/L nilotinib-treated cells as compared to untreated control group cells. Considering the results obtained in our study, nilotinib does not affect the functions of endothelial cells either in a prothrombotic or an antithrombotic fashion, despite a dose-dependent decline in cell viability. © The Author(s) 2014.

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

    Science.gov (United States)

    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 diet on markers of endothelial function in overweight/obese women with PCOS.

  8. Effects of Continuous and Accumulated Exercise on Endothelial Function in Rat Aorta.

    Science.gov (United States)

    Martinez, Juliana Edwiges; Taipeiro, Elane de Fátima; Chies, Agnaldo Bruno

    2017-04-01

    The practice of exercise in short bouts repeated throughout the day may be an alternative strategy to lift people out of physical inactivity. to evaluate if accumulated exercise, as occurs in continuous exercise training, improve endothelial function in rat aorta. Wistar male rats were divided into three groups: continuous exercise (CEx, 1 hour on the treadmill) or accumulated exercise (AEx, 4 bouts of 15 minutes / day) for 5 days/week for 8 weeks, or sedentary (SED). During the training period, body weight gain and increase in exercise performance were recorded. On sacrifice day, aorta was dissected into rings (3-5 mm) and mounted on the organ bath. Fitness was significantly greater in CEx and AEx rats as compared with SED animals. In addition, compared with the SED group, CEx animals had a lower body mass gain, and the aorta obtained from these animals had reduced contractile response to norepinephrine and greater acetylcholine-induced relaxation. These results were not observed in ACEx animals. Both CEx and AEx improved fitness, but only CEx led to reduced body weight gain and improved endothelial function. A prática de exercícios em sessões curtas que se repetem ao longo do dia pode ser uma alternativa para tirar as pessoas da inatividade física. Verificar se o exercício acumulado, tal como ocorre com o treinamento com exercício contínuo, melhora a função endotelial na aorta de ratos. Ratos Wistar machos foram divididos em 3 grupos: treinamento com exercício contínuo (ExC; 1 hora em esteira) ou com exercício acumulado (ExA; 4 sessões de 15 minutos ao longo do dia) por 5 dias/semana, durante 8 semanas, ou grupo sedentário (SED). Durante o treinamento, foram registrados o ganho de peso corporal e desempenho na esteira. No dia do sacrifício, anéis (3-5 mm) da aorta foram obtidos e montados em banho de órgãos. Animais ExC e ExA mostraram aptidão física significativamente maior em comparação com os SED. Paralelamente, em comparação com SED

  9. Adaptive Linear and Normalized Combination of Radial Basis Function Networks for Function Approximation and Regression

    Directory of Open Access Journals (Sweden)

    Yunfeng Wu

    2014-01-01

    Full Text Available This paper presents a novel adaptive linear and normalized combination (ALNC method that can be used to combine the component radial basis function networks (RBFNs to implement better function approximation and regression tasks. The optimization of the fusion weights is obtained by solving a constrained quadratic programming problem. According to the instantaneous errors generated by the component RBFNs, the ALNC is able to perform the selective ensemble of multiple leaners by adaptively adjusting the fusion weights from one instance to another. The results of the experiments on eight synthetic function approximation and six benchmark regression data sets show that the ALNC method can effectively help the ensemble system achieve a higher accuracy (measured in terms of mean-squared error and the better fidelity (characterized by normalized correlation coefficient of approximation, in relation to the popular simple average, weighted average, and the Bagging methods.

  10. Endothelial nitric oxide synthase single nucleotide polymorphism and left ventricular function in early chronic kidney disease.

    Directory of Open Access Journals (Sweden)

    Sourabh Chand

    Full Text Available Chronic kidney disease (CKD is associated with accelerated cardiovascular disease and heart failure. Endothelial nitric oxide synthase (eNOS Glu298Asp single nucleotide polymorphism (SNP genotype has been associated with a worse phenotype amongst patients with established heart failure and in patients with progression of their renal disease. The association of a cardiac functional difference in non-dialysis CKD patients with no known previous heart failure, and eNOS gene variant is investigated.140 non-dialysis CKD patients, who had cardiac magnetic resonance (CMR imaging and tissue doppler echocardiography as part of two clinical trials, were genotyped for eNOS Glu298Asp SNP retrospectively.The median estimated glomerular filtration rate (eGFR was 50 mls/min and left ventricular ejection fraction (LVEF was 74% with no overt diastolic dysfunction in this cohort. There were significant differences in LVEF across eNOS genotypes with GG genotype being associated with a worse LVEF compared to other genotypes (LVEF: GG 71%, TG 76%, TT 73%, p = 0.006. After multivariate analysis, (adjusting for age, eGFR, baseline mean arterial pressure, contemporary CMR heart rate, total cholesterol, high sensitive C-reactive protein, body mass index and gender GG genotype was associated with a worse LVEF, and increased LV end-diastolic and systolic index (p = 0.004, 0.049 and 0.009 respectively.eNOS Glu298Asp rs1799983 polymorphism in CKD patients is associated with relevant sub-clinical cardiac remodelling as detected by CMR. This gene variant may therefore represent an important genetic biomarker, and possibly highlight pathways for intervention, in these patients who are at particular risk of worsening cardiac disease as their renal dysfunction progresses.

  11. Resistance Exercise Restores Endothelial Function and Reduces Blood Pressure in Type 1 Diabetic Rats

    International Nuclear Information System (INIS)

    Mota, Marcelo Mendonça; Silva, Tharciano Luiz Teixeira Braga da; Fontes, Milene Tavares; Barreto, André Sales; Araújo, João Eliakim dos Santos; Oliveira, Antônio Cesar Cabral de; Wichi, Rogério Brandão; Santos, Márcio Roberto Viana

    2014-01-01

    Resistance exercise effects on cardiovascular parameters are not consistent. The effects of resistance exercise on changes in blood glucose, blood pressure and vascular reactivity were evaluated in diabetic rats. Wistar rats were divided into three groups: control group (n = 8); sedentary diabetic (n = 8); and trained diabetic (n = 8). Resistance exercise was carried out in a squat device for rats and consisted of three sets of ten repetitions with an intensity of 50%, three times per week, for eight weeks. Changes in vascular reactivity were evaluated in superior mesenteric artery rings. A significant reduction in the maximum response of acetylcholine-induced relaxation was observed in the sedentary diabetic group (78.1 ± 2%) and an increase in the trained diabetic group (95 ± 3%) without changing potency. In the presence of NG-nitro-L-arginine methyl ester, the acetylcholine-induced relaxation was significantly reduced in the control and trained diabetic groups, but not in the sedentary diabetic group. Furthermore, a significant increase (p < 0.05) in mean arterial blood pressure was observed in the sedentary diabetic group (104.9 ± 5 to 126.7 ± 5 mmHg) as compared to that in the control group. However, the trained diabetic group showed a significant decrease (p < 0.05) in the mean arterial blood pressure levels (126.7 ± 5 to 105.1 ± 4 mmHg) as compared to the sedentary diabetic group. Resistance exercise could restore endothelial function and prevent an increase in arterial blood pressure in type 1 diabetic rats

  12. Resistance Exercise Restores Endothelial Function and Reduces Blood Pressure in Type 1 Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Marcelo Mendonça Mota

    2014-07-01

    Full Text Available Background: Resistance exercise effects on cardiovascular parameters are not consistent. Objectives: The effects of resistance exercise on changes in blood glucose, blood pressure and vascular reactivity were evaluated in diabetic rats. Methods: Wistar rats were divided into three groups: control group (n = 8; sedentary diabetic (n = 8; and trained diabetic (n = 8. Resistance exercise was carried out in a squat device for rats and consisted of three sets of ten repetitions with an intensity of 50%, three times per week, for eight weeks. Changes in vascular reactivity were evaluated in superior mesenteric artery rings. Results: A significant reduction in the maximum response of acetylcholine-induced relaxation was observed in the sedentary diabetic group (78.1 ± 2% and an increase in the trained diabetic group (95 ± 3% without changing potency. In the presence of NG-nitro-L-arginine methyl ester, the acetylcholine-induced relaxation was significantly reduced in the control and trained diabetic groups, but not in the sedentary diabetic group. Furthermore, a significant increase (p < 0.05 in mean arterial blood pressure was observed in the sedentary diabetic group (104.9 ± 5 to 126.7 ± 5 mmHg as compared to that in the control group. However, the trained diabetic group showed a significant decrease (p < 0.05 in the mean arterial blood pressure levels (126.7 ± 5 to 105.1 ± 4 mmHg as compared to the sedentary diabetic group. Conclusions: Resistance exercise could restore endothelial function and prevent an increase in arterial blood pressure in type 1 diabetic rats.

  13. Resistance Exercise Restores Endothelial Function and Reduces Blood Pressure in Type 1 Diabetic Rats

    Energy Technology Data Exchange (ETDEWEB)

    Mota, Marcelo Mendonça; Silva, Tharciano Luiz Teixeira Braga da; Fontes, Milene Tavares; Barreto, André Sales; Araújo, João Eliakim dos Santos [Departamento de Fisiologia - Universidade Federal de Sergipe (UFS), São Cristóvão, SE (Brazil); Oliveira, Antônio Cesar Cabral de; Wichi, Rogério Brandão [Departamento de Educação Física - UFS, São Cristóvão, SE (Brazil); Santos, Márcio Roberto Viana, E-mail: marciorvsantos@bol.com.br [Departamento de Fisiologia - Universidade Federal de Sergipe (UFS), São Cristóvão, SE (Brazil)

    2014-07-15

    Resistance exercise effects on cardiovascular parameters are not consistent. The effects of resistance exercise on changes in blood glucose, blood pressure and vascular reactivity were evaluated in diabetic rats. Wistar rats were divided into three groups: control group (n = 8); sedentary diabetic (n = 8); and trained diabetic (n = 8). Resistance exercise was carried out in a squat device for rats and consisted of three sets of ten repetitions with an intensity of 50%, three times per week, for eight weeks. Changes in vascular reactivity were evaluated in superior mesenteric artery rings. A significant reduction in the maximum response of acetylcholine-induced relaxation was observed in the sedentary diabetic group (78.1 ± 2%) and an increase in the trained diabetic group (95 ± 3%) without changing potency. In the presence of NG-nitro-L-arginine methyl ester, the acetylcholine-induced relaxation was significantly reduced in the control and trained diabetic groups, but not in the sedentary diabetic group. Furthermore, a significant increase (p < 0.05) in mean arterial blood pressure was observed in the sedentary diabetic group (104.9 ± 5 to 126.7 ± 5 mmHg) as compared to that in the control group. However, the trained diabetic group showed a significant decrease (p < 0.05) in the mean arterial blood pressure levels (126.7 ± 5 to 105.1 ± 4 mmHg) as compared to the sedentary diabetic group. Resistance exercise could restore endothelial function and prevent an increase in arterial blood pressure in type 1 diabetic rats.

  14. Self-gated golden angle spiral cine MRI for coronary endothelial function assessment.

    Science.gov (United States)

    Bonanno, Gabriele; Hays, Allison G; Weiss, Robert G; Schär, Michael

    2018-08-01

    Depressed coronary endothelial function (CEF) is a marker for atherosclerotic disease, an independent predictor of cardiovascular events, and can be quantified non-invasively with ECG-triggered spiral cine MRI combined with isometric handgrip exercise (IHE). However, MRI-CEF measures can be hindered by faulty ECG-triggering, leading to prolonged breath-holds and degraded image quality. Here, a self-gated golden angle spiral method (SG-GA) is proposed to eliminate the need for ECG during cine MRI. SG-GA was tested against retrospectively ECG-gated golden angle spiral MRI (ECG-GA) and gold-standard ECG-triggered spiral cine MRI (ECG-STD) in 10 healthy volunteers. CEF data were obtained from cross-sectional images of the proximal right and left coronary arteries in a 3T scanner. Self-gating heart rates were compared to those from simultaneous ECG-gating. Coronary vessel sharpness and cross-sectional area (CSA) change with IHE were compared among the 3 methods. Self-gating precision, accuracy, and correlation-coefficient were 7.7 ± 0.5 ms, 9.1 ± 0.7 ms, and 0.93 ± 0.01, respectively (mean ± standard error). Vessel sharpness by SG-GA was equal or higher than ECG-STD (rest: 63.0 ± 1.7% vs. 61.3 ± 1.3%; exercise: 62.6 ± 1.3% vs. 56.7 ± 1.6%, P cine MRI method even when ECG is faulty or not available. Magn Reson Med 80:560-570, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  15. Effects of dark chocolate and cocoa consumption on endothelial function and arterial stiffness in overweight adults.

    Science.gov (United States)

    West, Sheila G; McIntyre, Molly D; Piotrowski, Matthew J; Poupin, Nathalie; Miller, Debra L; Preston, Amy G; Wagner, Paul; Groves, Lisa F; Skulas-Ray, Ann C

    2014-02-01

    The consumption of cocoa and dark chocolate is associated with a lower risk of CVD, and improvements in endothelial function may mediate this relationship. Less is known about the effects of cocoa/chocolate on the augmentation index (AI), a measure of vascular stiffness and vascular tone in the peripheral arterioles. We enrolled thirty middle-aged, overweight adults in a randomised, placebo-controlled, 4-week, cross-over study. During the active treatment (cocoa) period, the participants consumed 37 g/d of dark chocolate and a sugar-free cocoa beverage (total cocoa = 22 g/d, total flavanols (TF) = 814 mg/d). Colour-matched controls included a low-flavanol chocolate bar and a cocoa-free beverage with no added sugar (TF = 3 mg/d). Treatments were matched for total fat, saturated fat, carbohydrates and protein. The cocoa treatment significantly increased the basal diameter and peak diameter of the brachial artery by 6% (+2 mm) and basal blood flow volume by 22%. Substantial decreases in the AI, a measure of arterial stiffness, were observed in only women. Flow-mediated dilation and the reactive hyperaemia index remained unchanged. The consumption of cocoa had no effect on fasting blood measures, while the control treatment increased fasting insulin concentration and insulin resistance (P= 0·01). Fasting blood pressure (BP) remained unchanged, although the acute consumption of cocoa increased resting BP by 4 mmHg. In summary, the high-flavanol cocoa and dark chocolate treatment was associated with enhanced vasodilation in both conduit and resistance arteries and was accompanied by significant reductions in arterial stiffness in women.

  16. Endothelial mineralocorticoid receptor ablation does not alter blood pressure, kidney function or renal vessel contractility

    DEFF Research Database (Denmark)

    Laursen, Sidsel B.; Finsen, Stine; Marcussen, Niels

    2018-01-01

    found between the groups with respect to urinary excretion of sodium after 4 weeks of AngII infusion, or in urinary albumin excretion and kidney morphology. In conclusion, deletion of the EC-MR does not confer protection towards the development of hypertension, endothelial dysfunction of renal arteries......Aldosterone blockade confers substantial cardiovascular and renal protection. The effects of aldosterone on mineralocorticoid receptors (MR) expressed in endothelial cells (EC) within the renal vasculature have not been delineated. We hypothesized that lack of MR in EC may be protective in renal...... vasculature and examined this by ablating the Nr3c2 gene in endothelial cells (EC-MR) in mice. Blood pressure, heart rate and PAH clearance were measured using indwelling catheters in conscious mice. The role of the MR in EC on contraction and relaxation was investigated in the renal artery and in perfused...

  17. Iptakalim attenuates hypoxia-induced pulmonary arterial hypertension in rats by endothelial function protection.

    Science.gov (United States)

    Zhu, Rong; Bi, Li-Qing; Wu, Su-Ling; Li, Lan; Kong, Hui; Xie, Wei-Ping; Wang, Hong; Meng, Zi-Li

    2015-08-01

    The present study aimed to investigate the protective effects of iptakalim, an adenosine triphosphate (ATP)-sensitive potassium channel opener, on the inflammation of the pulmonary artery and endothelial cell injury in a hypoxia-induced pulmonary arterial hypertension (PAH) rat model. Ninety-six Sprague-Dawley rats were placed into normobaric hypoxia chambers for four weeks and were treated with iptakalim (1.5 mg/kg/day) or saline for 28 days. The right ventricle systolic pressures (RVSP) were measured and small pulmonary arterial morphological alterations were analyzed with hematoxylin and eosin staining. Enzyme-linked immunosorbent assay (ELISA) was performed to analyze the content of interleukin (IL)-1β and IL-10. Immunohistochemical analysis for ED1(+) monocytes was performed to detect the inflammatory cells surrounding the pulmonary arterioles. Western blot analysis was performed to analyze the expression levels of platelet endothelial cell adhesion molecule-1 (PECAM-1) and endothelial nitric oxide synthase (eNOS) in the lung tissue. Alterations in small pulmonary arteriole morphology and the ultrastructure of pulmonary arterial endothelial cells were observed via light and transmission electron microscopy, respectively. Iptakalim significantly attenuated the increase in mean pulmonary artery pressure, RVSP, right ventricle to left ventricle plus septum ratio and small pulmonary artery wall remodeling in hypoxia-induced PAH rats. Iptakalim also prevented an increase in IL-1β and a decrease in IL-10 in the peripheral blood and lung tissue, and alleviated inflammatory cell infiltration in hypoxia-induced PAH rats. Furthermore, iptakalim enhanced PECAM-1 and eNOS expression and prevented the endothelial cell injury induced by hypoxic stimuli. Iptakalim suppressed the pulmonary arteriole and systemic inflammatory responses and protected against the endothelial damage associated with the upregulation of PECAM-1 and eNOS, suggesting that iptakalim may represent a

  18. Test-retest reliability of pulse amplitude tonometry measures of vascular endothelial function: implications for clinical trial design.

    Science.gov (United States)

    McCrea, Cindy E; Skulas-Ray, Ann C; Chow, Mosuk; West, Sheila G

    2012-02-01

    Endothelial dysfunction is an important outcome for assessing vascular health in intervention studies. However, reliability of the standard non-invasive method (flow-mediated dilation) is a significant challenge for clinical applications and multicenter trials. We evaluated the repeatability of pulse amplitude tonometry (PAT) to measure change in pulse wave amplitude during reactive hyperemia (Itamar Medical Ltd, Caesarea, Israel). Twenty healthy adults completed two PAT tests (mean interval = 19.5 days) under standardized conditions. PAT-derived measures of endothelial function (reactive hyperemia index, RHI) and arterial stiffness (augmentation index, AI) showed strong repeatability (intra-class correlations = 0.74 and 0.83, respectively). To guide future research, we also analyzed sample size requirements for a range of effect sizes. A crossover design powered at 0.90 requires 28 participants to detect a 15% change in RHI. Our study is the first to show that PAT measurements are repeatable in adults over an interval greater than 1 week.

  19. S100A1 deficiency impairs postischemic angiogenesis via compromised proangiogenic endothelial cell function and nitric oxide synthase regulation.

    Science.gov (United States)

    Most, Patrick; Lerchenmüller, Carolin; Rengo, Giuseppe; Mahlmann, Adrian; Ritterhoff, Julia; Rohde, David; Goodman, Chelain; Busch, Cornelius J; Laube, Felix; Heissenberg, Julian; Pleger, Sven T; Weiss, Norbert; Katus, Hugo A; Koch, Walter J; Peppel, Karsten

    2013-01-04

    Mice lacking the EF-hand Ca2+ sensor S100A1 display endothelial dysfunction because of distorted Ca2+ -activated nitric oxide (NO) generation. To determine the pathophysiological role of S100A1 in endothelial cell (EC) function in experimental ischemic revascularization. Patients with chronic critical limb ischemia showed almost complete loss of S100A1 expression in hypoxic tissue. Ensuing studies in S100A1 knockout (SKO) mice subjected to femoral artery resection unveiled insufficient perfusion recovery and high rates of autoamputation. Defective in vivo angiogenesis prompted cellular studies in SKO ECs and human ECs, with small interfering RNA-mediated S100A1 knockdown demonstrating impaired in vitro and in vivo proangiogenic properties (proliferation, migration, tube formation) and attenuated vascular endothelial growth factor (VEGF)-stimulated and hypoxia-stimulated endothelial NO synthase (eNOS) activity. Mechanistically, S100A1 deficiency compromised eNOS activity in ECs by interrupted stimulatory S100A1/eNOS interaction and protein kinase C hyperactivation that resulted in inhibitory eNOS phosphorylation and enhanced VEGF receptor-2 degradation with attenuated VEGF signaling. Ischemic SKO tissue recapitulated the same molecular abnormalities with insufficient in vivo NO generation. Unresolved ischemia entailed excessive VEGF accumulation in SKO mice with aggravated VEGF receptor-2 degradation and blunted in vivo signaling through the proangiogenic phosphoinositide-3-kinase/Akt/eNOS cascade. The NO supplementation strategies rescued defective angiogenesis and salvaged limbs in SKO mice after femoral artery resection. Our study shows for the first time downregulation of S100A1 expression in patients with critical limb ischemia and identifies S100A1 as critical for EC function in postnatal ischemic angiogenesis. These findings link its pathological plasticity in critical limb ischemia to impaired neovascularization, prompting further studies to probe the

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

    Science.gov (United States)

    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.

  1. Blueberries Improve Endothelial Function, but Not Blood Pressure, in Adults with Metabolic Syndrome: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

    Directory of Open Access Journals (Sweden)

    April J. Stull

    2015-05-01

    Full Text Available 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.

  2. Physiological adaptation of endothelial function to pregnancy: systematic review and meta-analysis

    NARCIS (Netherlands)

    Balen, V.A.L. van; Gansewinkel, T.A.G. van; Haas, S.; Kuijk, S.M.J. van; Drongelen, J. van; Ghossein-Doha, C.; Spaanderman, M.E.A.

    2017-01-01

    OBJECTIVES: To establish reference values for flow-mediated dilatation (FMD) and brachial artery diameter (BAD) in pregnancy and to provide insight into the physiological and pathological course of endothelial adaptation throughout human singleton pregnancy. METHODS: A meta-analysis was performed

  3. Impaired coronary endothelial function in a rat model of spontaneous albuminuria

    NARCIS (Netherlands)

    Gschwend, Simone; Pinto-Sietsma, Sara-Joan; Buikema, Hendrik; Pinto, Yigal M.; van Gilst, Wiek H.; Schulz, Angela; de Zeeuw, Dick; Kreutz, Reinhold

    2002-01-01

    BACKGROUND: Albuminuria is an independent risk factor of coronary artery disease and has been proposed to reflect a general endothelial disorder. The Munich Wistar Frömter (MWF) rat strain develops spontaneous albuminuria and, therefore, may be an interesting experimental model to study alterations

  4. Effect of delayed onset prostacyclin on markers of endothelial function and damage after subarachnoid hemorrhage

    DEFF Research Database (Denmark)

    Gybel-Brask, Mikkel; Rasmussen, Rune; Stensballe, Jakob

    2017-01-01

    Background: Subarachnoid hemorrhage (SAH) is a neurological emergency. Delayed ischemic neurological deficit is one of the main causes of poor outcome after SAH and is probably caused, at least in part, by cerebral vasospasm. The pathophysiology of this is multifaceted, but endothelial damage...

  5. Neuronal function in male Sprague Dawley rats during normal ageing

    African Journals Online (AJOL)

    During normal ageing, there are physiological changes especially in high energy demanding tissues including the brain and skeletal muscles. Ageing may disrupt homeostasis and allow tissue vulnerability to disease. To establish an appropriate animal model which is readily available and will be useful to test therapeutic ...

  6. The effect of aprotinin on hypoxia-reoxygenation-induced changes in neutrophil and endothelial function.

    LENUS (Irish Health Repository)

    Harmon, D

    2012-02-03

    BACKGROUND AND OBJECTIVE: An acute inflammatory response associated with cerebral ischaemia-reperfusion contributes to the development of brain injury. Aprotinin has potential, though unexplained, neuroprotective effects in patients undergoing cardiac surgery. METHODS: Human neutrophil CD11 b\\/CD18, endothelial cell intercellular adhesion molecule-1 (ICAM-1) expression and endothelial interleukin (IL)-1beta supernatant concentrations in response to in vitro hypoxia-reoxygenation was studied in the presence or absence of aprotinin (1600 KIU mL(-1)). Adhesion molecule expression was quantified using flow cytometry and IL-1beta concentrations by enzyme-linked immunosorbent assay. Data were analysed using ANOVA and post hoc Student-Newman-Keuls test as appropriate. RESULTS: Exposure to 60-min hypoxia increased neutrophil CD11b expression compared to normoxia (170+\\/-46% vs. 91+\\/-27%, P = 0.001) (percent intensity of fluorescence compared to time 0) (n = 8). Hypoxia (60 min) produced greater upregulation of CD11b expression in controls compared to aprotinin-treated neutrophils [(170+\\/-46% vs. 129+\\/-40%) (P = 0.04)] (n = 8). Hypoxia-reoxygenation increased endothelial cell ICAM-1 expression (155+\\/-3.7 vs. 43+\\/-21 mean channel fluorescence, P = 0.0003) and IL-1beta supernatant concentrations compared to normoxia (3.4+\\/-0.4 vs. 2.6+\\/-0.2, P = 0.02) (n = 3). Hypoxia-reoxygenation produced greater upregulation of ICAM- 1 expression [(155+\\/-3.3 vs. 116+\\/-0.7) (P = 0.001)] and IL-1beta supernatant concentrations [(3.4+\\/-0.3 vs. 2.6+\\/-0.1) (P = 0.01)] in controls compared to aprotinin-treated endothelial cell preparation (n = 3). CONCLUSIONS: Hypoxia-reoxygenation-induced upregulation of neutrophil CD11b, endothelial cell ICAM-1 expression and IL-1beta concentrations is decreased by aprotinin at clinically relevant concentrations.

  7. In vitro recapitulation of functional microvessels for the study of endothelial shear response, nitric oxide and [Ca2+]i.

    Directory of Open Access Journals (Sweden)

    Xiang Li

    Full Text Available Microfluidic technologies enable in vitro studies to closely simulate in vivo microvessel environment with complexity. Such method overcomes certain constrains of the statically cultured endothelial monolayers and enables the cells grow under physiological range of shear flow with geometry similar to microvessels in vivo. However, there are still existing knowledge gaps and lack of convincing evidence to demonstrate and quantify key biological features of the microfluidic microvessels. In this paper, using advanced micromanufacturing and microfluidic technologies, we presented an engineered microvessel model that mimicked the dimensions and network structures of in vivo microvessels with a long-term and continuous perfusion capability, as well as high-resolution and real-time imaging capability. Through direct comparisons with studies conducted in intact microvessels, our results demonstrated that the cultured microvessels formed under perfused conditions recapitulated certain key features of the microvessels in vivo. In particular, primary human umbilical vein endothelial cells were successfully cultured the entire inner surfaces of the microchannel network with well-developed junctions indicated by VE-cadherin staining. The morphological and proliferative responses of endothelial cells to shear stresses were quantified under different flow conditions which was simulated with three-dimensional shear dependent numerical flow model. Furthermore, we successfully measured agonist-induced changes in intracellular Ca2+ concentration and nitric oxide production at individual endothelial cell levels using fluorescence imaging. The results were comparable to those derived from individually perfused intact venules. With in vivo validation of its functionalities, our microfluidic model demonstrates a great potential for biological applications and bridges the gaps between in vitro and in vivo microvascular research.

  8. Endothelial function and gene expression in perivascular adipose tissue from internal mammary arteries of obese patients with coronary artery disease.

    Science.gov (United States)

    Cybularz, Maria; Langbein, Heike; Zatschler, Birgit; Brunssen, Coy; Deussen, Andreas; Matschke, Klaus; Morawietz, Henning

    2017-11-01

    Obesity is a risk factor for endothelial dysfunction and atherosclerosis. However, perivascular adipose tissue can release adipokines and other unknown adipose-derived relaxing factors. Therefore, we investigated the impact of obesity on vascular function and expression of genes in perivascular adipose tissue from internal mammary arteries of patients with coronary artery disease undergoing coronary artery bypass grafting. The vessel function was compared between groups of patients with a body-mass index (BMI) between 25 and 30 kg/m 2 . The groups did not differ in age, gender (males), and ejection fraction. Vascular segments of internal mammary arteries were examined in a Mulvany myograph. Following preconstriction with noradrenaline, dose-response curves were assessed for relaxation with acetylcholine and sodium nitroprusside. Maximum contraction in response to potassium and noradrenaline was increased in obese patients with a BMI >30 kg/m 2 . EC50 of endothelium-dependent relaxation was impaired in patients with a BMI above 25, but below 30 kg/m 2 . Sodium nitroprusside-mediated maximal relaxation was not different between study groups. Integrin alpha X chain (ITGAX/CD11c) and macrophage mannose receptor (MRC1/CD206) expression was reduced in perivascular adipose tissue of patients with a BMI above 30 kg/m 2 , while adiponectin (ADPQ) expression was increased in the same tissue. Our data suggest a partially reduced endothelial function in internal mammary arteries of adipose patients with a BMI between 25 and 30 kg/m 2 undergoing coronary artery bypass grafting surgery. Increased adiponectin expression in perivascular tissue might contribute to maintenance of endothelial function in obese patients with a BMI above 30 kg/m 2 . Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Systemic Monocyte Chemotactic Protein-1 Inhibition Modifies Renal Macrophages and Restores Glomerular Endothelial Glycocalyx and Barrier Function in Diabetic Nephropathy.

    Science.gov (United States)

    Boels, Margien G S; Koudijs, Angela; Avramut, M Cristina; Sol, Wendy M P J; Wang, Gangqi; van Oeveren-Rietdijk, Annemarie M; van Zonneveld, Anton Jan; de Boer, Hetty C; van der Vlag, Johan; van Kooten, Cees; Eulberg, Dirk; van den Berg, Bernard M; IJpelaar, Daphne H T; Rabelink, Ton J

    2017-11-01

    Inhibition of monocyte chemotactic protein-1 (MCP-1) with the Spiegelmer emapticap pegol (NOX-E36) shows long-lasting albuminuria-reducing effects in diabetic nephropathy. MCP-1 regulates inflammatory cell recruitment and differentiation of macrophages. Because the endothelial glycocalyx is also reduced in diabetic nephropathy, we hypothesized that MCP-1 inhibition restores glomerular barrier function through influencing macrophage cathepsin L secretion, thus reducing activation of the glycocalyx-degrading enzyme heparanase. Four weeks of treatment of diabetic Apoe knockout mice with the mouse-specific NOX-E36 attenuated albuminuria without any change in systemic hemodynamics, despite persistent loss of podocyte function. MCP-1 inhibition, however, increased glomerular endothelial glycocalyx coverage, with preservation of heparan sulfate. Mechanistically, both glomerular cathepsin L and heparanase expression were reduced. MCP-1 inhibition resulted in reduced CCR2-expressing Ly6C hi monocytes in the peripheral blood, without affecting overall number of kidney macrophages at the tissue level. However, the CD206 + /Mac3 + cell ratio, as an index of presence of anti-inflammatory macrophages, increased in diabetic mice after treatment. Functional analysis of isolated renal macrophages showed increased release of IL-10, whereas tumor necrosis factor and cathepsin L release was reduced, further confirming polarization of tissue macrophages toward an anti-inflammatory phenotype during mouse-specific NOX-E36 treatment. We show that MCP-1 inhibition restores glomerular endothelial glycocalyx and barrier function and reduces tissue inflammation in the presence of ongoing diabetic injury, suggesting a therapeutic potential for NOX-E36 in diabetic nephropathy. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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) (Pchocolate ingestion, flow-mediated dilation was reduced after OGTT from 7.88±0.68 to 6.07±0.76 (P=0.027), 6.74±0.51 (P=0.046) at 1 and 2 h after the glucose load, respectively. Similarly, after white chocolate but not after dark chocolate, wave 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.

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

    Science.gov (United States)

    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.

  12. ENDOTHELIAL DYSFUNCTION IN ISCHEMIC HEART DISEASE

    Directory of Open Access Journals (Sweden)

    N. E. Zakirova

    2008-01-01

    Full Text Available Aim. To assess the role of endothelial vasodilating, vasoconstrictive and adhesive dysfunction in the development of angina pectoris (AP in patients with ischemic heart disease (IHD.Material and methods. 83 patients with IHD were included in the study. 30 patients had AP of functional class (FC-II, 27 patients - FC-III and 26 patients - FC-IV. The control group consisted of 25 healthy persons. Bicycle ergometry, daily ECG monitoring and echocardiography were used for verification of IHD. Endothelial vasodilating function was assessed by endothelium-dependent (EDVD and endothelium-independent vasodilatation (EIDVD of brachial artery. Vasoconstrictive function was assessed by the level of endothelin (ET-1. Endothelial adhesive function was evaluated by plasma concentration of intracellular adhesion molecules – JCAM-1, VCAM-1 and Е-selectin.Results. Normal EDVD and EIDVD were observed in patients with AP of FC-II. The more severe FC of AP the more prominent endothelial vasodilating dysfunction was revealed as well as the higher levels of ET-1 and intracellular adhesion molecules. Patients with AP of FC-IV had hyperexpression of JCAM-1, VCAM-1, Е-selectin and ET-1 and low levels of EDVD and EIDVD.Conclusion. Progression of IHD related with growing endothelial vasodilating, vasoconstrictive and adhesive dysfunction.

  13. Assessment of endothelial function during oral contraception in women with insulin-dependent diabetes mellitus

    DEFF Research Database (Denmark)

    Petersen, K R; Skouby, S O; Sidelmann, Johannes Jakobsen

    1994-01-01

    The effects of contraceptive steroids on the expression of endothelial homeostasis were examined by direct and indirect measures in women with insulin-dependent diabetes mellitus (IDDM) in a prospective nonrandomized controlled study. Study subjects were 13 women with uncomplicated IDDM treated w...... of the fibrinolytic system, is induced by hormonal treatment. Clinical and metabolic monitoring is recommended if the use of oral contraceptives in women with IDDM is extended.......The effects of contraceptive steroids on the expression of endothelial homeostasis were examined by direct and indirect measures in women with insulin-dependent diabetes mellitus (IDDM) in a prospective nonrandomized controlled study. Study subjects were 13 women with uncomplicated IDDM treated...... with a monophasic combination of 30 micrograms ethinyl estradiol and 75 micrograms gestodene for 12 consecutive cycles and 13 women of comparable diabetic status as control. During the study period, none of the participants developed increased renal albumin excretion, which was used as a direct measure...

  14. THE EFFECTS OF LONG-TERM REGULAR EXERCISE ON ENDOTHELIAL FUNCTIONS, INFLAMMATORY AND THROMBOTIC ACTIVITY IN MIDDLE-AGED, HEALTHY MEN

    Directory of Open Access Journals (Sweden)

    Metin Ergün

    2006-06-01

    Full Text Available As studying with population carrying no classical cardiovascular risk factors seems to be an advantage in isolating effects of regular exercise on endothelial functions, inflammatory and thrombotic activity; the present study was designed to evaluate the clear effects of long-term regular exercise in middle-aged, healthy men. A total of 32 regularly exercising (three times per week, 12.8 ± 6.8 years men (Group I, mean age = 53.2 ± 6. 1 yrs and 32 sex- and age-matched sedentary subjects (Group II, mean age = 51.0 ± 7.7 yrs were involved in the study. All participants were non-smokers and with no history of hypertension and diabetes. During one day preceding tests, the subjects refrained from training and maintained their normal diet. In all subjects, body mass index (BMI, percentage of body fat (% BF and maximal oxygen uptake (VO2max were calculated. Serum uric acid, glucose, HbA1c, lipids, high-sensitive C-reactive protein (hs-CRP, fibrinogen levels, white blood cell (WBC and platelet count were measured. Resting heart rates and blood pressures were recorded and standard exercise stress test was applied using the modified Bruce protocol. Flow-mediated and nitrate-induced dilatation (FMD and NID of the brachial artery and carotid intima-media thickness (cIMT were evaluated as markers of endothelial functions and early atherosclerosis. Mean BMI, % BF, systolic and diastolic blood pressures, WBC and platelet count, HbA1c, total and LDL cholesterol, hs-CRP and fibrinogen levels were similar between the groups. Group I had significantly lower serum glucose, uric acid and triglyceride (p < 0.05, p < 0.005 and p < 0.05, respectively and higher HDL cholesterol levels (p < 0.0001 than in Group II. FMD values were significantly higher in Group I than in Group II (p < 0.005 while there were no significant differences in NID and cIMT measures between the groups. VO2max and cIMT showed a negative correlation in Group I (r = -0.463, p < 0.0001. Negative

  15. Impact of endothelin blockade on acute exercise-induced changes in blood flow and endothelial function in type 2 diabetes mellitus.

    Science.gov (United States)

    Schreuder, Tim H A; van Lotringen, Jaap H; Hopman, Maria T E; Thijssen, Dick H J

    2014-09-01

    Positive vascular effects of exercise training are mediated by acute increases in blood flow. Type 2 diabetes patients show attenuated exercise-induced increases in blood flow, possibly mediated by the endothelin pathway, preventing an optimal stimulus for vascular adaptation. We examined the impact of endothelin receptor blockade (bosentan) on exercise-induced blood flow in the brachial artery and on pre- and postexercise endothelial function in type 2 diabetes patients (n = 9, 60 ± 7 years old) and control subjects (n = 10, 60 ± 5 years old). Subjects reported twice to the laboratory to perform hand-grip exercise in the presence of endothelin receptor blockade or placebo. We examined brachial artery endothelial function (via flow-mediated dilatation) before and after exercise, as well as blood flow during exercise. Endothelin receptor blockade resulted in a larger increase in blood flow during exercise in type 2 diabetes patients (P = 0.046), but not in control subjects (P = 0.309). Exercise increased shear rate across the exercise protocol, unaffected by endothelin receptor blockade. Exercise did not alter brachial artery diameter in either group, but endothelin receptor blockade resulted in a larger brachial artery diameter in type 2 diabetes patients (P = 0.033). Exercise significantly increased brachial artery flow-mediated dilatation in both groups, unaffected by endothelin receptor blockade. Endothelin receptor blockade increased exercise-induced brachial artery blood flow in type 2 diabetes patients, but not in control subjects. Despite this effect of endothelin receptor blockade on blood flow, we found no impact on baseline or post-exercise endothelial function in type 2 diabetes patients or control subjects, possibly related to normalization of the shear stimulus during exercise. The successful increase in blood flow during exercise in type 2 diabetes patients through endothelin receptor blockade may have beneficial effects in

  16. The Acute Effects of Grape Polyphenols Supplementation on Endothelial Function in Adults: Meta-Analyses of Controlled Trials

    Science.gov (United States)

    Li, Shao-Hua; Tian, Hong-Bo; Zhao, Hong-Jin; Chen, Liang-Hua; Cui, Lian-Qun

    2013-01-01

    Background The acute effects of grape polyphenols on endothelial function in adults are inconsistent. Here, we performed meta-analyses to determine these acute effects as measured by flow-mediated dilation (FMD). Methods Trials were searched in PubMed, Embase and the Cochrane Library database. Summary estimates of weighted mean differences (WMDs) and 95% CIs were obtained by using random-effects models. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity. The protocol details of our meta-analysis have been submitted to the PROSPERO register and our registration number is CRD42013004157. Results Nine studies were included in the present meta-analyses. The results showed that the FMD level was significantly increased in the initial 120 min after intake of grape polyphenols as compared with controls. Meta-regression and subgroup analyses were performed and showed that a health status was the main effect modifier of the significant heterogeneity. Subgroups indicated that intake of grape polyphenols could significantly increase FMD in healthy subjects, and the increased FMD appeared to be more obviously in subjects with high cardiovascular risk factors. Moreover, the peak effect of grape polyphenols on FMD in healthy subjects was found 30 min after ingestion, which was different from the effect in subjects with high cardiovascular risk factors, in whom the peak effect was found 60 min after ingestion. Conclusions Endothelial function can be significantly improved in healthy adults in the initial 2 h after intake of grape polyphenols. The acute effect of grape polyphenols on endothelial function may be more significant but the peak effect is delayed in subjects with a smoking history or coronary heart disease as compared with the healthy subjects. PMID:23894543

  17. The acute effects of grape polyphenols supplementation on endothelial function in adults: meta-analyses of controlled trials.

    Directory of Open Access Journals (Sweden)

    Shao-Hua Li

    Full Text Available BACKGROUND: The acute effects of grape polyphenols on endothelial function in adults are inconsistent. Here, we performed meta-analyses to determine these acute effects as measured by flow-mediated dilation (FMD. METHODS: Trials were searched in PubMed, Embase and the Cochrane Library database. Summary estimates of weighted mean differences (WMDs and 95% CIs were obtained by using random-effects models. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity. The protocol details of our meta-analysis have been submitted to the PROSPERO register and our registration number is CRD42013004157. RESULTS: Nine studies were included in the present meta-analyses. The results showed that the FMD level was significantly increased in the initial 120 min after intake of grape polyphenols as compared with controls. Meta-regression and subgroup analyses were performed and showed that a health status was the main effect modifier of the significant heterogeneity. Subgroups indicated that intake of grape polyphenols could significantly increase FMD in healthy subjects, and the increased FMD appeared to be more obviously in subjects with high cardiovascular risk factors. Moreover, the peak effect of grape polyphenols on FMD in healthy subjects was found 30 min after ingestion, which was different from the effect in subjects with high cardiovascular risk factors, in whom the peak effect was found 60 min after ingestion. CONCLUSIONS: Endothelial function can be significantly improved in healthy adults in the initial 2 h after intake of grape polyphenols. The acute effect of grape polyphenols on endothelial function may be more significant but the peak effect is delayed in subjects with a smoking history or coronary heart disease as compared with the healthy subjects.

  18. The acute effects of grape polyphenols supplementation on endothelial function in adults: meta-analyses of controlled trials.

    Science.gov (United States)

    Li, Shao-Hua; Tian, Hong-Bo; Zhao, Hong-Jin; Chen, Liang-Hua; Cui, Lian-Qun

    2013-01-01

    The acute effects of grape polyphenols on endothelial function in adults are inconsistent. Here, we performed meta-analyses to determine these acute effects as measured by flow-mediated dilation (FMD). Trials were searched in PubMed, Embase and the Cochrane Library database. Summary estimates of weighted mean differences (WMDs) and 95% CIs were obtained by using random-effects models. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity. The protocol details of our meta-analysis have been submitted to the PROSPERO register and our registration number is CRD42013004157. Nine studies were included in the present meta-analyses. The results showed that the FMD level was significantly increased in the initial 120 min after intake of grape polyphenols as compared with controls. Meta-regression and subgroup analyses were performed and showed that a health status was the main effect modifier of the significant heterogeneity. Subgroups indicated that intake of grape polyphenols could significantly increase FMD in healthy subjects, and the increased FMD appeared to be more obviously in subjects with high cardiovascular risk factors. Moreover, the peak effect of grape polyphenols on FMD in healthy subjects was found 30 min after ingestion, which was different from the effect in subjects with high cardiovascular risk factors, in whom the peak effect was found 60 min after ingestion. Endothelial function can be significantly improved in healthy adults in the initial 2 h after intake of grape polyphenols. The acute effect of grape polyphenols on endothelial function may be more significant but the peak effect is delayed in subjects with a smoking history or coronary heart disease as compared with the healthy subjects.

  19. Bipolar disorder and related mood states are not associated with endothelial function of small arteries in adults without heart disease.

    Science.gov (United States)

    Tong, Brian; Abosi, Oluchi; Schmitz, Samantha; Myers, Janie; Pierce, Gary L; Fiedorowicz, Jess G

    Individuals with bipolar disorder are at increased risk for adverse cardiovascular disease (CVD) events. This study aimed to assess endothelial function and wave reflection, a risk factor for CVD, as measured by finger plethysmography in bipolar disorder to investigate whether CVD risk was higher in bipolar disorder and altered during acute mood episodes. We hypothesized that EndoPAT would detect a lower reactive hyperemia index (RHI) and higher augmentation index (AIX) in individuals with bipolar disorder compared with controls. Second, we predicted lower RHI and higher AIX during acute mood episodes. Reactive hyperemia index and augmentation index, measures of microvascular endothelial function and arterial pressure wave reflection respectively, were assessed using the EndoPAT 2000 device in a sample of 56 participants with a DSM-IV diagnosis of bipolar I disorder with 82 measures spanning different mood states (mania, depression, euthymia) and cross-sectionally in 26 healthy controls. RHI and AIX were not different between adults with and without bipolar disorder (mean age 40.3 vs. 41.2years; RHI: 2.04±0.67 vs. 2.05±0.51; AIX@75 (AIX adjusted for heart rate of 75): 1.4±19.7 vs. 0.8±22.4). When modeled in linear mixed models with a random intercept (to account for repeated observations of persons with bipolar disorder) and adjusting for age and sex, there were no significant differences between those with bipolar disorder and controls (p=0.89 for RHI; p=0.85 for AIX@75). Microvascular endothelial function and wave reflection estimated by finger plethysmography were unable to detect differences between adults with and without bipolar disorder or changes with mood states. Future research is necessary to identify more proximal and sensitive, yet relevant, biomarkers of abnormal mood-related influences on CVD risk or must target higher risk samples. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. An analysis of endothelial microparticles as a function of cell surface antibodies and centrifugation techniques.

    Science.gov (United States)

    Venable, Adam S; Williams, Randall R; Haviland, David L; McFarlin, Brian K

    2014-04-01

    Chronic vascular disease is partially characterized by the presence of lesions along the vascular endothelial wall. Current FDA-approved clinical techniques lack the ability to measure very early changes in endothelial cell health. When endothelial cells are damaged, they release endothelial microparticles (EMPs) into circulation. Thus, blood EMP concentration may represent a useful cardiovascular disease biomarker. Despite the potential value of EMPs, current flow cytometry techniques may not consistently distinguish EMPs from other small cell particles. The purpose of this study was to use imaging flow cytometry to modify existing methods of identifying EMPs based on cell-surface receptor expression and visual morphology. Platelet poor plasma (PPP) was isolated using four different techniques, each utilizing a two-step serial centrifugation process. The cell-surface markers used in this study were selected based on those that are commonly reported in the literature. PPP (100μL) was labeled with CD31, CD42a, CD45, CD51, CD66b, and CD144 for 30-min in dark on ice. Based on replicated experiments, EMPs were best identified by cell-surface CD144 expression relative to other commonly reported EMP markers (CD31 & CD51). It is important to note that contaminating LMPs, GMPs, and PMPs were thought to be removed in the preparation of PPP. However, upon analysis of prepared samples staining CD31 against CD51 revealed a double-positive population that was less than 1% EMPs. In contrast, when using CD144 to identify EMPs, ~87% of observed particles were free of contaminating microparticles. Using a counterstain of CD42a, this purity can be improved to over 99%. More research is needed to understand how our improved EMP measurement method can be used in experimental models measuring acute vascular responses or chronic vascular diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

    OpenAIRE

    Heathfield, Sarah; Parker, Ben; Zeef, Leo; Bruce, Ian; Alexander, Yvonne; Collins, Fraser; Stone, Michael; Wang, Edward; Williams, Anwen S.; Wright, Helen L.; Thomas, Huw B.; Moots, Robert J.; Edwards, Steven W.; Bullock, Craig; Chapman, Victoria

    2017-01-01

    Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vas...

  2. Nonischemic changes in right ventricular function on exercise. Do normal volunteers differ from patients with normal coronary arteries

    International Nuclear Information System (INIS)

    Caplin, J.L.; Maltz, M.B.; Flatman, W.D.; Dymond, D.S.

    1988-01-01

    Factors other than ischemia may alter right ventricular function both at rest and on exercise. Normal volunteers differ from cardiac patients with normal coronary arteries with regard to their left ventricular response to exercise. This study examined changes in right ventricular function on exercise in 21 normal volunteers and 13 patients with normal coronary arteries, using first-pass radionuclide angiography. There were large ranges of right ventricular ejection fraction in the two groups, both at rest and on exercise. Resting right ventricular ejection fraction was 40.2 +/- 10.6% (mean +/- SD) in the volunteers and 38.6 +/- 9.7% in the patients, p = not significant, and on exercise rose significantly in both groups to 46.1 +/- 9.9% and 45.8 +/- 9.7%, respectively. The difference between the groups was not significant. In both groups some subjects with high resting values showed large decreases in ejection fraction on exercise, and there were significant negative correlations between resting ejection fraction and the change on exercise, r = -0.59 (p less than 0.01) in volunteers, and r = -0.66 (p less than 0.05) in patients. Older volunteers tended to have lower rest and exercise ejection fractions, but there was no difference between normotensive and hypertensive patients in their rest or exercise values. In conclusion, changes in right ventricular function on exercise are similar in normal volunteers and in patients with normal coronary arteries. Some subjects show decreases in right ventricular ejection fraction on exercise which do not appear to be related to ischemia

  3. Propranolol treatment of infantile hemangioma endothelial cells: A molecular analysis

    Science.gov (United States)

    STILES, JESSICA; AMAYA, CLARISSA; PHAM, ROBERT; ROWNTREE, REBECCA K.; LACAZE, MARY; MULNE, ARLYNN; BISCHOFF, JOYCE; KOKTA, VICTOR; BOUCHERON, LAURA E.; MITCHELL, DIANNE C.; BRYAN, BRAD A.

    2012-01-01

    Infantile hemangiomas (IHs) are non-malignant, largely cutaneous vascular tumors affecting approximately 5–10% of children to varying degrees. During the first year of life, these tumors are strongly proliferative, reaching an average size ranging from 2 to 20 cm. These lesions subsequently stabilize, undergo a spontaneous slow involution and are fully regressed by 5 to 10 years of age. Systemic treatment of infants with the non-selective β-adrenergic receptor blocker, propranolol, has demonstrated remarkable efficacy in reducing the size and appearance of IHs. However, the mechanism by which this occurs is largely unknown. In this study, we sought to understand the molecular mechanisms underlying the effectiveness of β blocker treatment in IHs. Our data reveal that propranolol treatment of IH endothelial cells, as well as a panel of normal primary endothelial cells, blocks endothelial cell proliferation, migration, and formation of the actin cytoskeleton coincident with alterations in vascular endothelial growth factor receptor-2 (VEGFR-2), p38 and cofilin signaling. Moreover, propranolol induces major alterations in the protein levels of key cyclins and cyclin-dependent kinase inhibitors, and modulates global gene expression patterns with a particular affect on genes involved in lipid/sterol metabolism, cell cycle regulation, angiogenesis and ubiquitination. Interestingly, the effects of propranolol were endothelial cell-type independent, affecting the properties of IH endothelial cells at similar levels to that observed in neonatal dermal microvascular and coronary artery endothelial cells. This data suggests that while propranolol markedly inhibits hemangioma and normal endothelial cell function, its lack of endothelial cell specificity hints that the efficacy of this drug in the treatment of IHs may be more complex than simply blockage of endothelial function as previously believed. PMID:23170111

  4. 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.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    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......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...

  6. 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.

  7. Passive heat therapy improves endothelial function, arterial stiffness and blood pressure in sedentary humans.

    Science.gov (United States)

    Brunt, Vienna E; Howard, Matthew J; Francisco, Michael A; Ely, Brett R; Minson, Christopher T

    2016-09-15

    A recent 30 year prospective study showed that lifelong sauna use reduces cardiovascular-related and all-cause mortality; however, the specific cardiovascular adaptations that cause this chronic protection are currently unknown. We investigated the effects of 8 weeks of repeated hot water immersion ('heat therapy') on various biomarkers of cardiovascular health in young, sedentary humans. We showed that, relative to a sham group which participated in thermoneutral water immersion, heat therapy increased flow-mediated dilatation, reduced arterial stiffness, reduced mean arterial and diastolic blood pressure, and reduced carotid intima media thickness, with changes all on par or greater than what is typically observed in sedentary subjects with exercise training. Our results show for the first time that heat therapy has widespread and robust effects on vascular function, and as such, could be a viable treatment option for improving cardiovascular health in a variety of patient populations, particularly those with limited exercise tolerance and/or capabilities. The majority of cardiovascular diseases are characterized by disorders of the arteries, predominantly caused by endothelial dysfunction and arterial stiffening. Intermittent hot water immersion ('heat therapy') results in elevations in core temperature and changes in cardiovascular haemodynamics, such as cardiac output and vascular shear stress, that are similar to exercise, and thus may provide an alternative means of improving health which could be utilized by patients with low exercise tolerance and/or capabilities. We sought to comprehensively assess the effects of 8 weeks of heat therapy on biomarkers of vascular function in young, sedentary subjects. Twenty young, sedentary subjects were assigned to participate in 8 weeks (4-5 times per week) of heat therapy (n = 10; immersion in a 40.5°C bath sufficient to maintain rectal temperature ≥ 38.5°C for 60 min per session) or thermoneutral water

  8. Vascular endothelium derived endothelin-1 is required for normal heart function after chronic pressure overload in mice.

    Directory of Open Access Journals (Sweden)

    Susi Heiden

    Full Text Available BACKGROUND: Endothelin-1 participates in the pathophysiology of heart failure. The reasons for the lack of beneficial effect of endothelin antagonists in heart failure patients remain however speculative. The anti-apoptotic properties of ET-1 on cardiomyocytes could be a reasonable explanation. We therefore hypothesized that blocking the pro-apoptotic TNF-α pathway using pentoxifylline could prevent the deleterious effect of the lack of ET-1 in a model for heart failure. METHODS: We performed transaortic constriction (TAC in vascular endothelial cells specific ET-1 deficient (VEETKO and wild type (WT mice (n = 5-9 and treated them with pentoxifylline for twelve weeks. RESULTS: TAC induced a cardiac hypertrophy in VEETKO and WT mice but a reduction of fractional shortening could be detected by echocardiography in VEETKO mice only. Cardiomyocyte diameter was significantly increased by TAC in VEETKO mice only. Pentoxifylline treatment prevented cardiac hypertrophy and reduction of fractional shortening in VEETKO mice but decreased fractional shortening in WT mice. Collagen deposition and number of apoptotic cells remained stable between the groups as did TNF-α, caspase-3 and caspase-8 messenger RNA expression levels. TAC surgery enhanced ANP, BNP and bcl2 expression. Pentoxifylline treatment reduced expression levels of BNP, bcl2 and bax. CONCLUSIONS: Lack of endothelial ET-1 worsened the impact of TAC-induced pressure overload on cardiac function, indicating the crucial role of ET-1 for normal cardiac function under stress. Moreover, we put in light a TNF-α-independent beneficial effect of pentoxifylline in the VEETKO mice suggesting a therapeutic potential for pentoxifylline in a subpopulation of heart failure patients at higher risk.

  9. Effects of Acute Active Video Games on Endothelial Function Following a High-Fat Meal in Overweight Adolescents.

    Science.gov (United States)

    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.

  10. Expression of BMP-2 in Vascular Endothelial Cells of Recipient May Predict Delayed Graft Function After Renal Transplantation

    Directory of Open Access Journals (Sweden)

    Nikolina Basic-Jukic

    2016-11-01

    Full Text Available Background/Aims: Delayed graft function (DGF is associated with adverse outcomes after renal transplantation. Bone morphogenetic protein-2 (BMP-2 is involved in both endothelial function and immunological events. We compared expression of BMP-2 in epigastric artery of renal transplant recipients with immediate graft function (IGF and DGF. Methods: 79 patients were included in this prospective study. Patients were divided in IGF group (64 patients and DGF group (15 patients. BMP-2 expression in intima media (BMP2m and endothelium (BMP2e of epigastric artery was assessed by immunohistochemistry. Results: Lower intensity of BMP2e staining was recorded in DGF compared to IGF. In DGF patients, 93% had no expression of BMP2e and 7% had 1st grade expression, compared to 45% and 41% in IGF group, respectively (P=0.001 (Pst grade expression. Patients who had BMP2e staining positive had lower odds for DGF (OR 0.059 [0.007, 0.477] and this remained significant even after adjustment for donor and recipient variables, cold ischemia time, and immunological matching (OR 0.038 [0.003, 0.492]. Conclusions: Our results demonstrate that BMP-2 expression in endothelial cells of epigastric arteries may predict development of DGF.

  11. Expression of BMP-2 in Vascular Endothelial Cells of Recipient May Predict Delayed Graft Function After Renal Transplantation.

    Science.gov (United States)

    Basic-Jukic, Nikolina; Gulin, Marijana; Hudolin, Tvrtko; Kastelan, Zeljko; Katalinic, Lea; Coric, Marijana; Veda, Marija Varnai; Ivkovic, Vanja; Kes, Petar; Jelakovic, Bojan

    2016-01-01

    Delayed graft function (DGF) is associated with adverse outcomes after renal transplantation. Bone morphogenetic protein-2 (BMP-2) is involved in both endothelial function and immunological events. We compared expression of BMP-2 in epigastric artery of renal transplant recipients with immediate graft function (IGF) and DGF. 79 patients were included in this prospective study. Patients were divided in IGF group (64 patients) and DGF group (15 patients). BMP-2 expression in intima media (BMP2m) and endothelium (BMP2e) of epigastric artery was assessed by immunohistochemistry. Lower intensity of BMP2e staining was recorded in DGF compared to IGF. In DGF patients, 93% had no expression of BMP2e and 7% had 1st grade expression, compared to 45% and 41% in IGF group, respectively (P=0.001) (P<0.001 for no expression and P = 0.015 for 1st grade expression). Patients who had BMP2e staining positive had lower odds for DGF (OR 0.059 [0.007, 0.477]) and this remained significant even after adjustment for donor and recipient variables, cold ischemia time, and immunological matching (OR 0.038 [0.003, 0.492]). Our results demonstrate that BMP-2 expression in endothelial cells of epigastric arteries may predict development of DGF. © 2016 The Author(s) Published by S. Karger AG, Basel.

  12. Effect of sequential mechanical ventilation on cardiac function, endothelial injury and oxidative stress response in patients with cor pulmonale

    Directory of Open Access Journals (Sweden)

    Yuan-Zeng He

    2017-08-01

    Full Text Available Objective: To study the effect of sequential mechanical ventilation on cardiac function, endothelial injury and oxidative stress response in patients with cor pulmonale (CCP. Methods: Patients with cor pulmonale complicated by respiratory failure who were treated in Dongfeng People’s Hospital between May 2014 and February 2017 were selected and randomly divided into the sequential group who received sequential mechanical ventilation combined with conventional therapy and the control group who received invasive positive pressure ventilation combined with conventional therapy. The serum levels of cardiac functionrelated neurohumoral indicators, endothelial injury indicators and oxidative stress response indicators were detected before treatment as well as 3 d and 7 d after treatment. Results: 3 d and 7 d after treatment, serum NT-proBNP, Copeptin, Ang-II, ALD, ET-1, vWF, sST2 levels of both groups of patients were significantly lower than those before treatment while NO, SOD, GSH-Px and T-AOC levels were significantly higher than those before treatment; serum NTproBNP, Copeptin, Ang-II, ALD, ET-1, vWF, sST2, NO, 8-iso-PGF2a, MDA, SOD, GSH-Px and T-AOC levels of sequential group 3 d after treatment were not significantly different from those of control group; serum NT-proBNP, Copeptin, Ang-II, ALDET-1, vWF, sST2, 8-iso- PGF2a and MDA levels of sequential group 7 d after treatment were significantly lower than those of control group while NO, SOD, GSH-Px and T-AOC levels were significantly higher than those of control group. Conclusion: Sequential mechanical ventilation for cor pulmonale can improve the cardiac function and reduce the degree of endothelial injury and oxidative stress response.

  13. A comparison of cell survival and heat shock protein expression after radiation in normal dermal fibroblasts, microvascular endothelial cells, and different head and neck squamous carcinoma cell lines.

    Science.gov (United States)

    Muschter, Dominique; Geyer, Fabian; Bauer, Richard; Ettl, Tobias; Schreml, Stephan; Haubner, Frank

    2018-01-06

    Head and neck squamous cell carcinoma (HNSCC) shows increased radioresistance due to the manipulation of homeostatic mechanisms like the heat shock response. This study intended to comparatively analyze effects of ionizing radiation on different HNSCC cell lines (PCI) and normal human dermal fibroblasts (NHFs) and human dermal microvascular endothelial cells (HDMECs) to uncover differences in radiation coping strategies. Proliferation (BrdU assay), apoptosis (caspase 3/7) and intracellular protein expression of heat shock protein (HSP)-70, and phosphorylated and total HSP27, determined by enzyme-linked immunosorbent assay (ELISA), were analyzed after exposure to increasing doses of ionizing radiation (2, 6, and 12 Gray, Gy). Cell count decreased dose-dependently, but PCI cell lines consistently showed higher numbers compared to NHF and HDMEC. Likewise, high doses reduced cell proliferation, but low-dose radiation (2 Gy) instead increased proliferation in PCI 9 and 52. Apoptosis was not detectable in PCI cell lines. Basic HSP70 expression was high in PCI cells with little additional increase by irradiation. PCI cells yielded high basic total HSP27 concentrations but irradiation dose-dependently increased HSP27 in HDMEC, NHF, and PCI cells. Phosphorylated HSP27 concentrations were highest in NHF. PCI cell lines showed higher resistance to dose-dependent reduction in cell number, proliferation, and protection from apoptosis compared to NHF and HDMEC. In parallel, we observed a high basic and radiation-induced expression of intracellular HSP70 leading to the assumption that the radioresistance of PCI cells is conferred by HSP70. HNSCC use HSP to escape radiation-induced apoptosis and certain subtypes might increase proliferation after low-dose irradiation.

  14. An Introduction to Normalization and Calibration Methods in Functional MRI

    Science.gov (United States)

    Liu, Thomas T.; Glover, Gary H.; Mueller, Bryon A.; Greve, Douglas N.; Brown, Gregory G.

    2013-01-01

    In functional magnetic resonance imaging (fMRI), the blood oxygenation level dependent (BOLD) signal is often interpreted as a measure of neural activity. However, because the BOLD signal reflects the complex interplay of neural, vascular, and metabolic processes, such an interpretation is not always valid. There is growing evidence that changes…

  15. Evaluation of an extended pancreatic function test in normal ...

    African Journals Online (AJOL)

    Exocrine pancreatic response was evaluated in patients with varying degrees of pancreatic damage and in control subjects by means of an extended pancreatic function test (PFT). A second injection of secretin and pancreozymin was given after completion of the standard test. The discriminatory value of the standard PFT ...

  16. An Important Method in the Investigation of Vascular Pathologies: Endothelial Cell Culture

    Directory of Open Access Journals (Sweden)

    Yusufhan Yazır

    2012-12-01

    Full Text Available Endothelial cells line the interior surface of blood vessels and form an interface between circulating blood in the lumen and the rest of the vessel wall. Endothelial cells are involved in many aspects of vascular biology, including barrier function, vasoconstriction, coagulation and inflamation. The endothelial cells in different organs have different functions and surface phenotype. These cells express prostoglandin-I2, platelet activating factor, collagen, endothelin-1, laminin, fibronectin and growth factors including platelet derived growth factor, fibroblast growth factor. İn the cell culture, cells can be isolated, maintened and proliferate in the laboratory conditions. The techniques of the cell culture have allowed scientists to use the cells in vitro for experimental studies, such as the production of vaccine, antibody and enzime, drug research, cell-cell interactions. Human umbilical vein endothelial cell is a good source for endothelial cell, because it is cheaper, easy to find and has the basic features of the normal endothelial cells.

  17. Overexpression of neurofilament H disrupts normal cell structure and function

    Science.gov (United States)

    Szebenyi, Gyorgyi; Smith, George M.; Li, Ping; Brady, Scott T.

    2002-01-01

    Studying exogenously expressed tagged proteins in live cells has become a standard technique for evaluating protein distribution and function. Typically, expression levels of experimentally introduced proteins are not regulated, and high levels are often preferred to facilitate detection. However, overexpression of many proteins leads to mislocalization and pathologies. Therefore, for normative studies, moderate levels of expression may be more suitable. To understand better the dynamics of intermediate filament formation, transport, and stability in a healthy, living cell, we inserted neurofilament heavy chain (NFH)-green fluorescent protein (GFP) fusion constructs in adenoviral vectors with tetracycline (tet)-regulated promoters. This system allows for turning on or off the synthesis of NFH-GFP at a selected time, for a defined period, in a dose-dependent manner. We used this inducible system for live cell imaging of changes in filament structure and cell shape, motility, and transport associated with increasing NFH-GFP expression. Cells with low to intermediate levels of NFH-GFP were structurally and functionally similar to neighboring, nonexpressing cells. In contrast, overexpression led to pathological alterations in both filament organization and cell function. Copyright 2002 Wiley-Liss, Inc.

  18. Normal function of immunologic stem cells from aged mice

    International Nuclear Information System (INIS)

    Harrison, D.E.; Doubleday, J.W.

    1975-01-01

    Marrow or spleen grafts from aged donor mice produced antibody-forming cells as effectively as did grafts from younger controls in recipients tested 3 to 10 months after the transplantation. All recipients were lethally irradiated, and the T6 chromosome marker was used to demonstrate that they were populated by donor cell lines. Recipients of aged or younger control grafts gave similar responses when stimulated with varying doses of antigen and when tested at different times after the transplantation except in two cases. Recipients of aged spleen grafts gave significantly lower responses than younger controls for the first few weeks after the transplantation. If recipients had been thymectomized before lethal irradiation, aged cell lines (pooled marrow and spleen cells) gave only 37 percent of the responses of younger controls. Given sufficient time and intact young recipients, immunologic stem cell lines from old donors populated recipients with cells having normal immune responses. These results suggest that age-related immunologic defects are not intrinsically timed in the precursor cell lines that populate the immune system. (U.S.)

  19. Renal functional reserve in children with apparently normal congenital solitary functioning kidney.

    Science.gov (United States)

    Peco-Antić, Amira; Paripović, Dušan; Kotur-Stevuljević, Jelena; Stefanović, Aleksandra; Sćekić, Gordana; Miloševski-Lomić, Gordana

    2012-10-01

    The aim of the study was to investigate renal functional reserve (RFR) and to assess its relationship with serum cystatin C and blood pressure in children with apparently normal congenital solitary functioning kidney (SFK). RFR was obtained from the difference of endogenous creatinine clearance (CrCs) before and after a meat-free oral protein load (OPL) in the patients who were pre-treated with cimetidine. Serum cystatin C and urinary protein excretion were determined before and after OPL. Among 22 patients (13 boys), aged 9.5 ± 4.3 years, 72.7% had increased serum cystatin C, and 54.5% had decreased RFR. Following OPL, CrCs and urine creatinine increased, while serum creatinine and cystatin C remained unchanged. The multiple regression analysis demonstrated that cystatin C could predict more than 90% of RFR variability. Half of the patients with apparently normal SFK had decreased RFR. Serum cystatin C is one of the best predictors of RFR. Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  20. Structural and Functional Characterization of Two Alternative Splicing Variants of Mouse Endothelial Cell-Specific Chemotaxis Regulator (ECSCR

    Directory of Open Access Journals (Sweden)

    Yongchang Chang

    2012-04-01

    Full Text Available Endothelial cells (ECs that line the lumen of blood vessels are important players in blood vessel formation, and EC migration is a key component of the angiogenic process. Thus, identification of genes that are specifically or preferentially expressed in vascular ECs and in-depth understanding of their biological functions may lead to discovery of new therapeutic targets. We have previously reported molecular characterization of human endothelial cell-specific molecule 2 (ECSM2/endothelial cell-specific chemotaxis regulator (ECSCR. In the present study, we cloned two mouse full-length cDNAs by RT-PCR, which encode two putative ECSCR isoform precursors with considerable homology to the human ECSCR. Nucleotide sequence and exon-intron junction analyses suggested that they are alternative splicing variants (ECSCR isoform-1 and -2, differing from each other in the first and second exons. Quantitative RT-PCR results revealed that isoform-2 is the predominant form, which was most abundant in heart, lung, and muscles, and moderately abundant in uterus and testis. In contrast, the expression of isoform-1 seemed to be more enriched in testis. To further explore their potential cellular functions, we expressed GFP- and FLAG-tagged ECSCR isoforms, respectively, in an ECSCR deficient cell line (HEK293. Interestingly, the actual sizes of either ECSCR-GFP or -FLAG fusion proteins detected by immunoblotting are much larger than their predicted sizes, suggesting that both isoforms are glycoproteins. Fluorescence microscopy revealed that both ECSCR isoforms are localized at the cell surface, which is consistent with the structural prediction. Finally, we performed cell migration assays using mouse endothelial MS1 cells overexpressing GFP alone, isoform-1-GFP, and isoform-2-GFP, respectively. Our results showed that both isoforms significantly inhibited vascular epidermal growth factor (VEGF-induced cell migration. Taken together, we have provided several lines

  1. Surface-mediated functional gene delivery: an effective strategy for enhancing competitiveness of endothelial cells over smooth muscle cells.

    Science.gov (United States)

    Chang, Hao; Ren, Ke-feng; Wang, Jin-Lei; Zhang, He; Wang, Bai-liang; Zheng, Shan-mei; Zhou, Yuan-yuan; Ji, Jian

    2013-04-01

    The non-biorecognition of general biomaterials and inherent biospecificity of biological systems pose key challenges to the optimal functions of medical devices. In this study, we constructed the surface-mediated functional gene delivery through layer-by-layer self-assembly of protamine sulfate (PrS) and plasmid DNA encoding hepatocyte growth factor (HGF), aiming at specific enhancing endothelial cells (EC) compeititiveness over smooth muscle cells (SMC). Characterizations of the (PrS/HGF-pDNA) multilayered films present the linear buildup with homogeneous and flat topographical feature. The amount of DNA can be easily controlled. By using these multilayered films, both human umbilical vein endothelial cells (HUVEC) and human umbilical artery smooth muscle cells (HUASMC) can be directly transfected when they contact with the multilayered films. On transfection, increasing secretion of HGF has been detected in both HUVEC and HUASMC culture, which leads to selective promotion of HUVEC proliferation. In the co-culture experiment, we also exhibit the promoted and hindered growth of HUVEC and HUASMC, respectively, which could be attributed to the inverse influence of HUVEC on HUASMC. These results collectively demonstrate that our system can be served as a powerful tool for enhancing competitiveness of EC over SMC, which opens perspectives for the regulation of intercellular competitiveness in the field of interventional therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Curcumin induces therapeutic angiogenesis in a diabetic mouse hindlimb ischemia model via modulating the function of endothelial progenitor cells.

    Science.gov (United States)

    You, Jinzhi; Sun, Jiacheng; Ma, Teng; Yang, Ziying; Wang, Xu; Zhang, Zhiwei; Li, Jingjing; Wang, Longgang; Ii, Masaaki; Yang, Junjie; Shen, Zhenya

    2017-08-03

    Neovascularization is impaired in diabetes mellitus, which leads to the development of peripheral arterial disease and is mainly attributed to the dysfunction of endothelial progenitor cells (EPCs). Previous studies proved the promotional effect of curcumin on neovascularization in wound healing of diabetes. Thus, we hypothesize that curcumin could promote neovascularization at sites of hindlimb ischemia in diabetes and might take effect via modulating the function of EPCs. Streptozotocin-induced type 1 diabetic mice and nondiabetic mice both received unilateral hindlimb ischemic surgery. Curcumin was then administrated to the mice by lavage for 14 days consecutively. Laser Doppler perfusion imaging was conducted to demonstrate the blood flow reperfusion. Capillary density was measured in the ischemic gastrocnemius muscle. In addition, angiogenesis, migration, proliferation abilities, and senescence were determined in EPCs isolated from diabetic and nondiabetic mice. Quantitative PCR was then used to determine the mRNA expression of vascular endothelial growth factor (VEGF) and angiopoetin-1 (Ang-1) in EPCs. Curcumin application to type 1 diabetic mice significantly improved blood reperfusion and increased the capillary density in ischemic hindlimbs. The in-vitro study also revealed that the angiogenesis, migration, and proliferation abilities of EPCs and the number of senescent EPCs were reversed by curcumin application. Quantitative PCR confirmed the overexpression of VEGF-A and Ang-1 in EPCs after curcumin treatment. Curcumin could enhance neovascularization via promoting the function of EPCs in a diabetic mouse hindlimb ischemia model.

  3. Effect of exercise intensity on postprandial lipemia, markers of oxidative stress, and endothelial function after a high-fat meal.

    Science.gov (United States)

    Lopes Krüger, Renata; Costa Teixeira, Bruno; Boufleur Farinha, Juliano; Cauduro Oliveira Macedo, Rodrigo; Pinto Boeno, Francesco; Rech, Anderson; Lopez, Pedro; Silveira Pinto, Ronei; Reischak-Oliveira, Alvaro

    2016-12-01

    The aim of this study was to compare the effects of 2 different exercise intensities on postprandial lipemia, oxidative stress markers, and endothelial function after a high-fat meal (HFM). Eleven young men completed 2-day trials in 3 conditions: rest, moderate-intensity exercise (MI-Exercise) and heavy-intensity exercise (HI-Exercise). Subjects performed an exercise bout or no exercise (Rest) on the evening of day 1. On the morning of day 2, an HFM was provided. Blood was sampled at fasting (0 h) and every hour from 1 to 5 h during the postprandial period for triacylglycerol (TAG), thiobarbituric acid reactive substance (TBARS), and nitrite/nitrate (NOx) concentrations. Flow-mediated dilatation (FMD) was also analyzed. TAG concentrations were reduced in exercise conditions compared with Rest during the postprandial period (P postprandial TAG enhancement. Conversely, MI-Exercise can be beneficial to attenuate the susceptibility of oxidative damage induced by an HFM and to increase endothelial function in the fasted state compared with Rest.

  4. Excessive dietary phosphorus intake impairs endothelial function in young healthy men: a time- and dose-dependent study.

    Science.gov (United States)

    Nishi, Tamae; Shuto, Emi; Ogawa, Mariko; Ohya, Miho; Nakanishi, Misaki; Masuda, Masashi; Katsumoto, Misaki; Yamanaka-Okumura, Hisami; Sakai, Tohru; Takeda, Eiji; Sakaue, Hiroshi; Taketani, Yutaka

    2015-01-01

    Excessive dietary phosphorus (P) has been speculated to be a risk factor for cardiovascular disease (CVD). Here, we performed a double-blinded crossover study to investigate the time- and dose-dependent effects of dietary P intake on endothelial function in healthy subjects. Sixteen healthy male volunteers were given meals containing 400, 800, and 1,200 mg P (P400, P800, and P1200 meals, respectively) with at least 7 days between doses. There were no differences in nutritional composition among the experimental diets except for P content. Blood biochemistry data and flow-mediated dilation (%FMD) of the brachial artery were measured while fasted, at 0 h, 1 h, 2 h, and 4 h after meal ingestion, and the next morning while fasted. The P800 and P1200 meals significantly increased serum P levels at 1-4 h after ingestion. A significant decrease in %FMD was observed between 1-4 h,while the P400 meal did not affect %FMD. We observed no differences among meals in serum P levels or %FMD the next morning. A significant negative correlation was observed between %FMD and serum P. These results indicate that excessive dietary P intake can acutely impair endothelial function in healthy people.

  5. Effect of Regular Aerobic Activity in Young Healthy Athletes on Profile of Endothelial Function and Platelet Activity

    Directory of Open Access Journals (Sweden)

    Katarzyna Podgórska

    2017-01-01

    Full Text Available The aim of the study was to assess the impact of regular professional sports activity on the endothelial and platelet function in young men. The studied group were 79 young men (18–40 y, 25 athletes and 54 without any regular physical activity. The nitric oxide (NO metabolic pathway intermediates, oxidative stress markers, mediators of inflammation, and platelet aggregation were measured. Flow mediated dilation (FMD was studied before and after intravenous 16,0 g L-arginine infusion, which was repeated after oral administration of acetylsalicylic acid (ASA-75 mg/day for 4 days. Both groups had similar demographic characteristics. In the athletes, there was significantly higher hsCRP level, better serum lipid profile, and lower pulse pressure. Greater baseline FMD in athletes and in response to L-arginine disappeared following ASA treatment. There were no differences in the levels of the NO pathway metabolites. The control group was characterized by higher PAI-1 following ASA treatment and sICAM-1 both at baseline and after ASA, but no differences in MDA and 6-keto-PGF-1 alpha and platelet aggregation were noted. Regular professional physical activity modulates endothelial but not platelet function and may thus exert an effect on overall cardiovascular risk.

  6. Dynamics of endothelial function violation in patients with arterial hypertension with moderate cardiovascular risk and antihypertensive therapy treatment influence

    Directory of Open Access Journals (Sweden)

    T. S. Turlyun

    2016-08-01

    stabilization of blood pressure, indices of lipid profile lowering, the tendency to endothelial function improvement, especially with losartan potassium therapy.

  7. Exposure to lipopolysaccharide and/or unconjugated bilirubin impair the integrity and function of brain microvascular endothelial cells.

    Directory of Open Access Journals (Sweden)

    Filipa L Cardoso

    Full Text Available BACKGROUND: Sepsis and jaundice are common conditions in newborns that can lead to brain damage. Though lipopolysaccharide (LPS is known to alter the integrity of the blood-brain barrier (BBB, little is known on the effects of unconjugated bilirubin (UCB and even less on the joint effects of UCB and LPS on brain microvascular endothelial cells (BMEC. METHODOLOGY/PRINCIPAL FINDINGS: Monolayers of primary rat BMEC were treated with 1 µg/ml LPS and/or 50 µM UCB, in the presence of 100 µM human serum albumin, for 4 or 24 h. Co-cultures of BMEC with astroglial cells, a more complex BBB model, were used in selected experiments. LPS led to apoptosis and UCB induced both apoptotic and necrotic-like cell death. LPS and UCB led to inhibition of P-glycoprotein and activation of matrix metalloproteinases-2 and -9 in mono-cultures. Transmission electron microscopy evidenced apoptotic bodies, as well as damaged mitochondria and rough endoplasmic reticulum in BMEC by either insult. Shorter cell contacts and increased caveolae-like invaginations were noticeable in LPS-treated cells and loss of intercellular junctions was observed upon treatment with UCB. Both compounds triggered impairment of endothelial permeability and transendothelial electrical resistance both in mono- and co-cultures. The functional changes were confirmed by alterations in immunostaining for junctional proteins β-catenin, ZO-1 and claudin-5. Enlargement of intercellular spaces, and redistribution of junctional proteins were found in BMEC after exposure to LPS and UCB. CONCLUSIONS: LPS and/or UCB exert direct toxic effects on BMEC, with distinct temporal profiles and mechanisms of action. Therefore, the impairment of brain endothelial integrity upon exposure to these neurotoxins may favor their access to the brain, thus increasing the risk of injury and requiring adequate clinical management of sepsis and jaundice in the neonatal period.

  8. Decreased endothelial nitric oxide synthase expression and function contribute to impaired mitochondrial biogenesis and oxidative stress in fetal lambs with persistent pulmonary hypertension.

    Science.gov (United States)

    Afolayan, Adeleye J; Eis, Annie; Alexander, Maxwell; Michalkiewicz, Teresa; Teng, Ru-Jeng; Lakshminrusimha, Satyan; Konduri, Girija G

    2016-01-01

    Impaired vasodilation in persistent pulmonary hypertension of the newborn (PPHN) is characterized by mitochondrial dysfunction. We investigated the hypothesis that a decreased endothelial nitric oxide synthase level leads to impaired mitochondrial biogenesis and function in a lamb model of PPHN induced by prenatal ductus arteriosus constriction. We ventilated PPHN lambs with 100% O2 alone or with inhaled nitric oxide (iNO). We treated pulmonary artery endothelial cells (PAECs) from normal and PPHN lambs with detaNONOate, an NO donor. We observed decreased mitochondrial (mt) DNA copy number, electron transport chain (ETC) complex subunit levels, and ATP levels in PAECs and lung tissue of PPHN fetal lambs at baseline compared with gestation matched controls. Phosphorylation of AMP-activated kinase (AMPK) and levels of peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC-1α) and sirtuin-1, which facilitate mitochondrial biogenesis, were decreased in PPHN. Ventilation with 100% O2 was associated with larger decreases in ETC subunits in the lungs of PPHN lambs compared with unventilated PPHN lambs. iNO administration, which facilitated weaning of FiO2 , partly restored mtDNA copy number, ETC subunit levels, and ATP levels. DetaNONOate increased eNOS phosphorylation and its interaction with heat shock protein 90 (HSP90); increased levels of superoxide dismutase 2 (SOD2) mRNA, protein, and activity; and decreased the mitochondrial superoxide levels in PPHN-PAECs. Knockdown of eNOS decreased ETC protein levels in control PAECs. We conclude that ventilation with 100% O2 amplifies oxidative stress and mitochondrial dysfunction in PPHN, which are partly improved by iNO and weaning of oxygen. Copyright © 2016 the American Physiological Society.

  9. Purinergic glio-endothelial coupling during neuronal activity: role of P2Y1 receptors and eNOS in functional hyperemia in the mouse somatosensory cortex.

    Science.gov (United States)

    Toth, Peter; Tarantini, Stefano; Davila, Antonio; Valcarcel-Ares, M Noa; Tucsek, Zsuzsanna; Varamini, Behzad; Ballabh, Praveen; Sonntag, William E; Baur, Joseph A; Csiszar, Anna; Ungvari, Zoltan

    2015-12-01

    Impairment of moment-to-moment adjustment of cerebral blood flow (CBF) via neurovascular coupling is thought to play a critical role in the genesis of cognitive impairment associated with aging and pathological conditions associated with accelerated cerebromicrovascular aging (e.g., hypertension, obesity). Although previous studies demonstrate that endothelial dysfunction plays a critical role in neurovascular uncoupling in these conditions, the role of endothelial NO mediation in neurovascular coupling responses is not well understood. To establish the link between endothelial function and functional hyperemia, neurovascular coupling responses were studied in mutant mice overexpressing or deficient in endothelial NO synthase (eNOS), and the role of P2Y1 receptors in purinergic glioendothelial coupling was assessed. We found that genetic depletion of eNOS (eNOS(-/-)) and pharmacological inhibition of NO synthesis significantly decreased the CBF responses in the somatosensory cortex evoked by whisker stimulation and by administration of ATP. Overexpression of eNOS enhanced NO mediation of functional hyperemia. In control mice, the selective and potent P2Y1 receptor antagonist MRS2179 attenuated both whisker stimulation-induced and ATP-mediated CBF responses, whereas, in eNOS(-/-) mice, the inhibitory effects of MRS2179 were blunted. Collectively, our findings provide additional evidence for purinergic glio-endothelial coupling during neuronal activity, highlighting the role of ATP-mediated activation of eNOS via P2Y1 receptors in functional hyperemia. Copyright © 2015 the American Physiological Society.

  10. Intranasal Oxytocin Normalizes Amygdala Functional Connectivity in Posttraumatic Stress Disorder.

    Science.gov (United States)

    Koch, Saskia B J; van Zuiden, Mirjam; Nawijn, Laura; Frijling, Jessie L; Veltman, Dick J; Olff, Miranda

    2016-07-01

    The neuropeptide oxytocin (OT) has been suggested as a promising pharmacological agent for medication-enhanced psychotherapy in posttraumatic stress disorder (PTSD) because of its anxiolytic and prosocial properties. We therefore investigated the behavioral and neurobiological effects of a single intranasal OT administration (40 IU) in PTSD patients. We conducted a randomized, placebo-controlled, cross-over resting-state fMRI study in male and female police officers with (n=37, 21 males) and without PTSD (n=40, 20 males). We investigated OT administration effects on subjective anxiety and functional connectivity of basolateral (BLA) and centromedial (CeM) amygdala subregions with prefrontal and salience processing areas. In PTSD patients, OT administration resulted in decreased subjective anxiety and nervousness. Under placebo, male PTSD patients showed diminished right CeM to left ventromedial prefrontal cortex (vmPFC) connectivity compared with male trauma-exposed controls, which was reinstated after OT administration. Additionally, female PTSD patients showed enhanced right BLA to bilateral dorsal anterior cingulate cortex (dACC) connectivity compared with female trauma-exposed controls, which was dampened after OT administration. Although caution is warranted, our findings tentatively suggest that OT has the potential to diminish anxiety and fear expression of the amygdala in PTSD, either via increased control of the vmPFC over the CeM (males) or via decreased salience processing of the dACC and BLA (females). Our findings add to accumulating evidence that OT administration could potentially enhance treatment response in PTSD.

  11. Daily consumption for six weeks of a lignan complex isolated from flaxseed does not affect endothelial function in healthy postmenopausal women

    DEFF Research Database (Denmark)

    Hallund, Jesper; Tetens, Inge; Bügel, Susanne

    2006-01-01

    function. Healthy postmenopausal women (n = 22) completed a randomized, double-blind, placebo-controlled, crossover study. Women consumed daily a low-fat muffin, with or without a lignan complex, for 6 wk, separated by a 6-wk washout period. Flow-mediated, endothelium-dependent vasodilatation (FMD...... on endothelial function in healthy postmenopausal women....

  12. Acute effects of beer on endothelial function and hemodynamics: a single-blind, crossover study in healthy volunteers.

    Science.gov (United States)

    Karatzi, Kalliopi; Rontoyanni, Victoria G; Protogerou, Athanase D; Georgoulia, Aggeliki; Xenos, Konstantinos; Chrysou, John; Sfikakis, Petros P; Sidossis, Labros S

    2013-09-01

    Moderate consumption of beer is associated with lower cardiovascular (CV) risk. The goal of this study was to determine the effect of beer consumption on CV risk. To explore the underlying mechanisms, we studied the acute effects of the constituents of beer (alcohol and antioxidants), on established predictors of CV risk: endothelial function, aortic stiffness, pressure wave reflections and aortic pressure. In a randomized, single-blind, crossover study, 17 healthy, non-smoking, men (ages 28.5 ± 5.2 y with body mass index 24.4 ± 2.5 kg/m(2)) consumed on three separate occasions, at least 1 wk apart: 1. 400 mL of beer and 400 mL water, 2. 800 mL of dealcoholized beer (same amount of polyphenols as in the 400 mL of beer), and 3. 67 mL of vodka and 733 mL water (same amount of alcohol as in the 400 mL of beer). Each time aortic stiffness (pulse wave velocity), pressure wave reflections (AΙx), aortic and brachial pressure (Sphygmocor device), and endothelial function (brachial flow mediated dilatation) were assessed at fast and 1 and 2 h postprandial. Aortic stiffness was significantly and similarly reduced by all three interventions. However, endothelial function was significantly improved only after beer consumption (average 1.33%, 95% confidence interval [CI] 0.15-2.53). Although wave reflections were significantly reduced by all three interventions (average of beer: 9.1%, dealcoholized beer: 2.8%, vodka 8.5%, all CI within limits of significance), the reduction was higher after beer consumption compared with dealcoholized beer (P = 0.018). Pulse pressure amplification (i.e., brachial/aortic) was increased by all three test drinks. Beer acutely improves parameters of arterial function and structure, in healthy non-smokers. This benefit seems to be mediated by the additive or synergistic effects of alcohol and antioxidants and merits further investigation. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. GroEL1, a heat shock protein 60 of Chlamydia pneumoniae, impairs neovascularization by decreasing endothelial progenitor cell function.

    Directory of Open Access Journals (Sweden)

    Yi-Wen Lin

    Full Text Available The number and function of endothelial progenitor cells (EPCs are sensitive to hyperglycemia, hypertension, and smoking in humans, which are also associated with the development of atherosclerosis. GroEL1 from Chlamydia pneumoniae has been found in atherosclerotic lesions and is related to atherosclerotic pathogenesis. However, the actual effects of GroEL1 on EPC function are unclear. In this study, we investigate the EPC function in GroEL1-administered hind limb-ischemic C57BL/B6 and C57BL/10ScNJ (a toll-like receptor 4 (TLR4 mutation mice and human EPCs. In mice, laser Doppler imaging, flow cytometry, and immunohistochemistry were used to evaluate the degree of neo-vasculogenesis, circulating level of EPCs, and expression of CD34, vWF, and endothelial nitric oxide synthase (eNOS in vessels. Blood flow in the ischemic limb was significantly impaired in C57BL/B6 but not C57BL/10ScNJ mice treated with GroEL1. Circulating EPCs were also decreased after GroEL1 administration in C57BL/B6 mice. Additionally, GroEL1 inhibited the expression of CD34 and eNOS in C57BL/B6 ischemic muscle. In vitro, GroEL1 impaired the capacity of differentiation, mobilization, tube formation, and migration of EPCs. GroEL1 increased senescence, which was mediated by caspases, p38 MAPK, and ERK1/2 signaling in EPCs. Furthermore, GroEL1 decreased integrin and E-selectin expression and induced inflammatory responses in EPCs. In conclusion, these findings suggest that TLR4 and impaired NO-related mechanisms could contribute to the reduced number and functional activity of EPCs in the presence of GroEL1 from C. pneumoniae.

  14. The effect of pre-dive ingestion of dark chocolate on endothelial function after a scuba dive.

    Science.gov (United States)

    Theunissen, Sigrid; Balestra, Costantino; Boutros, Antoine; De Bels, David; Guerrero, François; Germonpré, Peter

    2015-03-01

    The aim of the study was to observe the effects of dark chocolate on endothelial function after scuba diving. Forty-two male scuba divers were divided into two groups: a control (n=21) and a chocolate group (n=21). They performed a 33-metres deep scuba-air dive for 20 minutes in a diving pool (Nemo 33, Brussels). Water temperature was 33⁰C. The chocolate group ingested 30 g of dark chocolate (86% cocoa) 90 minutes before the dive. Flow-mediated dilatation (FMD), digital photoplethysmography and nitric oxide (NO) and peroxynitrites (ONOO-) levels were measured before and after the scuba dive in both groups. A significant decrease in FMD was observed in the control group after the dive (91±7% (mean±95% confidence interval) of pre-dive values; Pdive values; Pdives. No variation of circulating NO level was observed in the control group whereas an increase was shown in the chocolate group (154±73% of pre-dive values; P=0.04). A significant reduction in ONOO- was observed in the control group (84±12% of pre-dive values; P=0.003) whereas no variation was shown after the dive with chocolate intake (100±28% of pre-dive values; ns). Ingestion of 30 g of dark chocolate 90 minutes before scuba diving prevented post-dive endothelial dysfunction, as the antioxidants contained in dark chocolate probably scavenge free radicals.

  15. Bartonella henselae: subversion of vascular endothelial cell functions by translocated bacterial effector proteins.

    Science.gov (United States)

    Pulliainen, Arto Tapio; Dehio, Christoph

    2009-03-01

    Bartonella henselae (Bh) is a worldwide distributed zoonotic pathogen. Depending on the immune status of the infected individual this bacterium can cause a wide spectrum of clinical manifestations, ranging from cat scratch disease (CSD) to bacillary angiomatosis (BA) and bacillary peliosis (BP). BA and BP are characterized by tumor-like lesions at the skin or in the inner organs, respectively. These structures display pathological sprouting of capillaries with enlarged and hyperproliferated vascular endothelial cells (ECs) that are frequently found in close association with bacteria. Here we review the cellular changes observed upon Bh infection of ECs in vitro and outline the role of the VirB type IV secretion system (T4SS) and its translocated effector proteins in the modulation of EC signalling cascades. The current model how this virulence system could contribute to the vasoproliferative activity of Bh is described.

  16. Mechano-sensing and transduction by endothelial surface glycocalyx: composition, structure, and function.

    Science.gov (United States)

    Fu, Bingmei M; Tarbell, John M

    2013-01-01

    The endothelial cells (ECs) lining every blood vessel wall are constantly exposed to the mechanical forces generated by blood flow. The EC responses to these hemodynamic forces play a critical role in the homeostasis of the circulatory system. To ensure proper EC mechano-sensing and transduction, there are a variety of mechano-sensors and transducers that have been identified on the EC surface, intra- and trans-EC membrane and within the EC cytoskeleton. Among them, the most recent candidate is the endothelial surface glycocalyx (ESG), which is a matrix-like thin layer covering the luminal surface of the EC. It consists of various proteoglycans, glycosaminoglycans, and plasma proteins, and is close to other prominent EC mechano-sensors and transducers. The ESG thickness was found to be in the order of 0.1-1 µm by different visualization techniques and in different types of vessels. Detailed analysis on the electron microscopy (EM) images of the microvascular ESG revealed a quasi-periodic substructure with the ESG fiber diameter of 10-12 and 20 nm spacing between adjacent fibers. Atomic force microscopy and optical tweezers were applied to investigate the mechanical properties of the ESG on the cultured EC monolayers and in solutions. Enzymatic degradation of specific ESG glycosaminoglycan components was used to directly elucidate the role of the ESG in EC mechano-sensing and transduction by measuring the shear-induced productions of nitric oxide and prostacyclin, two characteristic responses of the ECs to the flow. The unique location, composition, and structure of the ESG determine its role in EC mechano-sensing and transduction. Copyright © 2013 Wiley Periodicals, Inc.

  17. The Comparison of the Executive-Neurological Functions of the Narcotic Addicted and Normal Adults

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    Fereshteh Amini

    2010-05-01

    Full Text Available Aim: The purpose of present research was the comparison of executive-neurological functions of narcotics addicted and normal adults. Method: In this causal-comparative study 38 narcotics addicted person selected of two addiction treatment clinics in Tehran, and 38 normal persons selected through available sampling. The both groups assessed by neuropsychological tests namely: the Wisconsin classification cards. Results: The analysis of data indicated the significant difference on executive functions of addicted and normal groups. That is addicted group were poorer than normal group on executive functions. Conclusion: The findings of present research showed the addicts have weaker executive functions than the normal persons. In other words, the addicts showed impairments on cognitive flexibility and formation of change concepts.

  18. ACL-RSI and KOOS Measures Predict Normal Knee Function after ACL-SPORTS Training

    OpenAIRE

    White, Kathleen; Zeni, Joseph; Snyder-Mackler, Lynn

    2014-01-01

    Objectives: After anterior cruciate ligament reconstruction (ACLR) athletes commonly report increased fear of re-injury and below normal knee function. Implementing a post-operative training protocol (ACL-SPORTS Training) to improve patient perceived knee function, may improve short term outcomes after surgery. Identifying pre-training measures that predict normal knee function after training may allow us to determine who may respond to the treatment intervention. The purpose of this study wa...

  19. Consumption of water containing over 3.5 mg of dissolved hydrogen could improve vascular endothelial function

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    Sakai T

    2014-10-01

    Full Text Available Takaaki Sakai,1 Bunpei Sato,2 Koji Hara,3 Yuichi Hara,3 Yuji Naritomi,3 Samon Koyanagi,1 Hiroshi Hara,3 Tetsuhiko Nagao,4 Toru Ishibashi51Department of Cardiology, Haradoi Hospital, Fukuoka, Japan; 2MiZ Company Limited, Fujisawa, Kanagawa, Japan; 3Department of Internal Medicine, Haradoi Hospital, Fukuoka, Japan; 4Midorino Clinic, Aoba, Higashi-ku, Fukuoka, Japan; 5Department of Rheumatology and Orthopedic Surgery, Haradoi Hospital, Fukuoka, Japan Background: The redox imbalance between nitric oxide and superoxide generated in the endothelium is thought to play a pivotal role in the development of endothelial dysfunction. A third reactive oxygen species (ROS, H2O2, is known to have both beneficial and detrimental effects on the vasculature. Nonetheless, the influence of the hydroxyl radical, a byproduct of H2O2 decay, is unclear, and there is no direct evidence that the hydroxyl radical impairs endothelial function in conduit arteries. Molecular hydrogen (H2 neutralizes detrimental ROS, especially the hydroxyl radical. Objectives: To assess the influence of the hydroxyl radical on the endothelium and to confirm that a gaseous antioxidant, H2, can be a useful modulator of blood vessel function. Methods: The efficacy of water containing a high concentration of H2 was tested by measuring flow-mediated dilation (FMD of the brachial artery (BA. The subjects were randomly divided into two groups: the high-H2 group, who drank high-H2 water containing 7 ppm H2 (3.5 mg H2 in 500 mL water; and the placebo group. Endothelial function was evaluated by measuring the FMD of the BA. After measurement of diameter of the BA and FMD at baseline, volunteers drank the high-H2 water or placebo water immediately and with a 30-minute interval; FMD was compared to baseline. Results: FMD increased in the high-H2 group (eight males; eight females from 6.80%±1.96% to 7.64%±1.68% (mean ± standard deviation and decreased from 8.07%±2.41% to 6.87%±2.94% in the placebo

  20. Effects of Music Therapy on Endothelial Function in Patients With Coronary Artery Disease Participating in Aerobic Exercise Therapy.

    Science.gov (United States)

    Deljanin Ilic, Marina; Pavlovic, Radmila F; Kocic, Gordana; Simonovic, Dejan; Lazarevic, Gordana

    2017-05-01

    Context • Pleasant music that evokes a positive emotional response may activate brain pathways of the insular cortex, central nucleus of the amygdala, and lateral hypothalamus, which are involved in the integration of emotional and ambient sensory input, with corresponding autonomic responses. Exercise training can improve endothelium-dependent vasodilatation, both in epicardial coronary vessels and in resistance vessels, for patients with coronary heart disease. Objective • The aim of the present study was to evaluate the effects on endothelial function when patients with stable coronary artery disease (CAD) listened to their favorite music. Design • The study was a randomized controlled trial. Setting • The study occurred at the Institute of Cardiology, Niska Banja, Faculty of Medicine, University of Nis (Nis, Serbia). Participants • Participants were 74 patients with stable CAD. Intervention • Participants were randomly assigned to 1 of 3 groups: (1) exercise training only (T) group (n = 33), (2) listening to music and exercise training (MT) group (n = 31), and listening to music only (M) group (n = 10). Participants in the T and MT groups received usual medical care and underwent 3 wk of supervised aerobic exercise training. In addition to the exercise training, participants in the MT group listened to their favorite music for 1.5 h every day. Participants in the M group received the usual medical care and listened to their favorite music for 1.5 h every day. Outcome Measures • At baseline and postintervention, outcomes were assessed through measurement of the changes in circulating blood markers of endothelial function-the stable end product of nitric oxide (NOx), asymmetric dimethylarginine, symmetric dimethylarginine, and xanthine oxidase-and through the results of submaximal or symptom-limited exercise test. Results • After 3 wk, the NOx significantly increased in both in MT and T groups, with P exercise capacity, which increased in the T

  1. Age-related normal structural and functional ventricular values in cardiac function assessed by magnetic resonance

    International Nuclear Information System (INIS)

    Fiechter, Michael; Gaemperli, Oliver; Kaufmann, Philipp A; Fuchs, Tobias A; Gebhard, Catherine; Stehli, Julia; Klaeser, Bernd; Stähli, Barbara E; Manka, Robert; Manes, Costantina; Tanner, Felix C

    2013-01-01

    The heart is subject to structural and functional changes with advancing age. However, the magnitude of cardiac age-dependent transformation has not been conclusively elucidated. This retrospective cardiac magnetic resonance (CMR) study included 183 subjects with normal structural and functional ventricular values. End systolic volume (ESV), end diastolic volume (EDV), and ejection fraction (EF) were obtained from the left and the right ventricle in breath-hold cine CMR. Patients were classified into four age groups (20–29, 30–49, 50–69, and ≥70 years) and cardiac measurements were compared using Pearson’s rank correlation over the four different groups. With advanced age a slight but significant decrease in ESV (r=−0.41 for both ventricles, P<0.001) and EDV (r=−0.39 for left ventricle, r=−0.35 for right ventricle, P<0.001) were observed associated with a significant increase in left (r=0.28, P<0.001) and right (r=0.27, P<0.01) ventricular EF reaching a maximal increase in EF of +8.4% (P<0.001) for the left and +6.1% (P<0.01) for the right ventricle in the oldest compared to the youngest patient group. Left ventricular myocardial mass significantly decreased over the four different age groups (P<0.05). The aging process is associated with significant changes in left and right ventricular EF, ESV and EDV in subjects with no cardiac functional and structural abnormalities. These findings underline the importance of using age adapted values as standard of reference when evaluating CMR studies

  2. 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.

  3. Taurine and magnesium supplementation enhances the function of endothelial progenitor cells through antioxidation in healthy men and spontaneously hypertensive rats.

    Science.gov (United States)

    Katakawa, Mayumi; Fukuda, Noboru; Tsunemi, Akiko; Mori, Mari; Maruyama, Takashi; Matsumoto, Taro; Abe, Masanori; Yamori, Yukio

    2016-12-01

    Endothelial damage is repaired by endothelial progenitor cells (EPCs), which are pivotal in preventing cardiovascular diseases and prolonging lifespan. The WHO Cardiovascular Diseases and Alimentary Comparison Study demonstrated that dietary taurine and magnesium (Mg) intake suppresses cardiovascular diseases. We herein evaluate the effects of taurine and Mg supplementation on EPC function and oxidative stress in healthy men and spontaneously hypertensive rats (SHRs). Healthy men received taurine (3 g per day) or Mg (340 mg per day) for 2 weeks. SHRs and Wistar-Kyoto (WKY) rats were housed with high-salt drinking water (1% NaCl). The SHRs received 3% taurine solution and/or a high-Mg (600 mg per 100 g) diet for 4 weeks. Their peripheral blood mononuclear cells were separated to quantify EPC colony formation. Oxidative stress markers in their peripheral blood were evaluated using a free radical analytical system and a thiobarbituric acid reactive substance (TBARS) assay. Taurine and Mg supplementation significantly increased EPC colony numbers and significantly decreased free radical levels and TBARS scores in healthy men. Taurine and Mg supplementation significantly increased EPC colony numbers and significantly decreased TBARS scores and free radical levels in SHRs. Nicotinamide adenine dinucleotide phosphate oxidase component mRNA expression was significantly higher in the renal cortex of salt-loaded SHRs than in WKY rats, in which it was suppressed by taurine and Mg supplementation. Taurine and Mg supplementation increased EPC colony formation in healthy men and improved impaired EPC function in SHRs through antioxidation, indicating that the dietary intake of taurine and Mg may prolong lifespan by preventing the progression of cardiovascular diseases.

  4. BH4 improves postprandial endothelial function after a high-fat meal in men and postmenopausal women.

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    Shah, Yashesh; Bass, Leon; Davison, Gareth W; Seigler, Nichole; Pollock, Jennifer S; Thomas, Jeff; Harris, Ryan A

    2017-05-01

    The timing and duration of menopause is important when evaluating the risk for cardiovascular disease in postmenopausal women, likely related in part to nitric oxide (NO) bioavailability. The flow-mediated dilation (FMD) test is a noninvasive assessment of NO bioavailability in humans, and tetrahydrobiopterin (BH4) is essential for NO synthesis. A high-fat meal (HFM) has been used to increase lipemia and reduce NO bioavailability. Thus, this study sought to determine if menopausal transition has any impact on the postprandial endothelial function response to a HFM, and evaluate the effect of BH4 on postprandial endothelial function in postmenopausal women and men. Utilizing a randomized, double-blind, placebo-controlled design, sex-steroid hormones and FMD were determined in 30 older adults (10 postmenopausal women aged below 3 y [W y [W > 10], and 10 men) at baseline and 4 hours after the ingestion of a HFM alone or a HFM with BH4 (HFM + BH4; 5 mg/kg). Data are presented as mean ± SEM. Independent of treatment, postprandial testosterone was significantly (P  10 group. In addition, concentrations of progesterone were higher (P = 0.019) and the testosterone/estradiol ratio was lower (P = 0.026) in all groups after the ingestion of HFM + BH4 compared with the ingestion of HFM alone. Overall, an increase in FMD was observed after the ingestion of HFM + BH4 (Δ1.9% ± 0.6%), whereas no change in FMD was observed after the ingestion of HFM alone (Δ-0.7% ± 0.6%). Co-ingestion of BH4 with a HFM not only alters the sex-steroid hormone ratio, it improves postprandial FMD after a HFM regardless of postmenopause status or sex.

  5. Insulin therapy does not interfere with venous endothelial function evaluation in patients with type 2 diabetes mellitus

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    Antônio Marcos Vargas da Silva

    2010-01-01

    Full Text Available INTRODUCTION: Endothelium-dependent dilation is improved in insulin-treated diabetic patients, but this effect is probably due to improved glycemic control. The objective of the present study was to compare endothelium-dependent dilation in patients with well-controlled type 2 diabetes who are or are not using insulin as part of their therapy. METHODS: We studied 27 patients with type 2 diabetes (11 women, 60.3 years ± 6 years, with HbA1c < 7% and no nephropathy, including 16 patients treated with anti-diabetic agents (No-Ins, 8 women and 11 patients treated with insulin alone or in combination with anti-diabetic agents (Ins, 3 women. Endothelial function was evaluated by the dorsal hand vein technique, which measures changes in vein diameter in response to phenylephrine, acetylcholine (endothelium-dependent vasodilation and sodium nitroprusside (endothelium-independent vasodilation. RESULTS: Age, systolic blood pressure (No-Ins: 129.4 mmHg ± 11.8 mmHg, Ins: 134.8 mmHg ± 12.0 mmHg; P= 0.257, HbA1c, lipids and urinary albumin excretion rate [No-Ins: 9 mg/24 h (0-14.1 mg/24 h vs. Ins: 10.6 mg/24 h (7.5-14.4 mg/24 h, P=0.398] were similar between groups. There was no difference between endothelium-dependent vasodilation of the No-Ins group (59.3% ± 26.5% vs. the Ins group (54.0% ± 16.3%; P=0.526. Endothelium-independent vasodilation was also similar between the No-Ins (113.7% ± 35.3% and Ins groups (111.9% ± 28.5%; P=0.888. CONCLUSIONS: Subcutaneous insulin therapy does not interfere with venous endothelial function in type 2 diabetes when glycemic and blood pressure control are stable.

  6. Insulin therapy does not interfere with venous endothelial function evaluation in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Silva, Antônio Marcos Vargas da; Penno, Luciana de Moraes; Bertoluci, Marcello Casaccia; Irigoyen, Maria Cláudia; Schaan, Beatriz D'Agord

    2010-01-01

    Endothelium-dependent dilation is improved in insulin-treated diabetic patients, but this effect is probably due to improved glycemic control. The objective of the present study was to compare endothelium-dependent dilation in patients with well-controlled type 2 diabetes who are or are not using insulin as part of their therapy. We studied 27 patients with type 2 diabetes (11 women, 60.3 years ± 6 years, with HbA1c < 7% and no nephropathy), including 16 patients treated with anti-diabetic agents (No-Ins, 8 women) and 11 patients treated with insulin alone or in combination with anti-diabetic agents (Ins, 3 women). Endothelial function was evaluated by the dorsal hand vein technique, which measures changes in vein diameter in response to phenylephrine, acetylcholine (endothelium-dependent vasodilation) and sodium nitroprusside (endothelium-independent vasodilation). Age, systolic blood pressure (No-Ins: 129.4 mmHg ± 11.8 mmHg, Ins: 134.8 mmHg ± 12.0 mmHg; P= 0.257), HbA1c, lipids and urinary albumin excretion rate [No-Ins: 9 mg/24 h (0-14.1 mg/24 h) vs. Ins: 10.6 mg/24 h (7.5-14.4 mg/24 h), P=0.398] were similar between groups. There was no difference between endothelium-dependent vasodilation of the No-Ins group (59.3% ± 26.5%) vs. the Ins group (54.0% ± 16.3%; P=0.526). Endothelium-independent vasodilation was also similar between the No-Ins (113.7% ± 35.3%) and Ins groups (111.9% ± 28.5%; P=0.888). Subcutaneous insulin therapy does not interfere with venous endothelial function in type 2 diabetes when glycemic and blood pressure control are stable.

  7. Functional cross-talk between endothelial muscarinic and α2-adrenergic receptors in rabbit cerebral arteries

    Science.gov (United States)

    Thorin, Eric

    1998-01-01

    Interactions between two classes of receptors have been observed in several cell lines and preparations. The aim of this work was to assess the impact of simultaneous stimulation of endothelial muscarinic and α2-adrenergic receptors (α2-AR) on vascular reactivity.Rabbit middle cerebral arteries were isolated and changes in isometric tension were recorded in the presence of indomethacin.Inhibition of nitric oxide (NO) synthase with Nω-nitro-L-arginine (L-NOARG, 100 μmol l−1) revealed α-AR-dependent contractions. Pre-addition of acetylcholine (ACH, 1 μmol l−1) augmented oxymetazoline (OXY, 10 μmol l−1, α2-AR agonist)-, but decreased phenylephrine (PE, 10 μmol l−1, α1-AR agonist)-induced contraction (P<0.05). The effects of ACH were endothelium-dependent.Vessels were precontracted with 40 mmol l−1 KCl-physiological salt solution (PSS) in the absence of L-NOARG, or PE or OXY in the presence of L-NOARG. In the presence of high external K+ or PE, ACH induced a potent relaxation (P<0.05). In the presence of OXY, however, ACH mediated contraction (P<0.05).After pertussis toxin (PTX, inactivator of Gαi/o proteins) pre-treatment, α2-AR-dependent contractions were abolished. Forty mmol l−1 KCl-PSS induced contraction was not altered by PTX whereas ACH-induced relaxation was augmented (P<0.05).To investigate if endothelin-1 (ET-1) intervened in the endothelium-dependent contractile response to ACH in the presence of OXY-dependent tone, vessels were incubated in the presence of BQ123 (1 μmol l−1), an ETA receptor antagonist. OXY-mediated tone was not affected by BQ123; however, ACH-induced contraction was reversed to a relaxation (P<0.05).These data indicate that activation of endothelial α2-AR triggers an endothelium-dependent, ET-1 mediated, contraction to ACH. This suggests that activation of α2-AR affects muscarinic receptor/G protein coupling leading to an opposite biological effect. PMID:9863646

  8. Far infra-red therapy promotes ischemia-induced angiogenesis in diabetic mice and restores high glucose-suppressed endothelial progenitor cell functions

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    Huang Po-Hsun

    2012-08-01

    Full Text Available Abstract Background Far infra-red (IFR therapy was shown to exert beneficial effects in cardiovascular system, but effects of IFR on endothelial progenitor cell (EPC and EPC-related vasculogenesis remain unclear. We hypothesized that IFR radiation can restore blood flow recovery in ischemic hindlimb in diabetic mice by enhancement of EPCs functions and homing process. Materials and methods Starting at 4 weeks after the onset of diabetes, unilateral hindlimb ischemia was induced in streptozotocine (STZ-induced diabetic mice, which were divided into control and IFR therapy groups (n = 6 per group. The latter mice were placed in an IFR dry sauna at 34°C for 30 min once per day for 5 weeks. Results Doppler perfusion imaging demonstrated that the ischemic limb/normal side blood perfusion ratio in the thermal therapy group was significantly increased beyond that in controls, and significantly greater capillary density was seen in the IFR therapy group. Flow cytometry analysis showed impaired EPCs (Sca-1+/Flk-1+ mobilization after ischemia surgery in diabetic mice with or without IFR therapy (n = 6 per group. However, as compared to those in the control group, bone marrow-derived EPCs differentiated into endothelial cells defined as GFP+/CD31+ double-positive cells were significantly increased in ischemic tissue around the vessels in diabetic mice that received IFR radiation. In in-vitro studies, cultured EPCs treated with IFR radiation markedly augmented high glucose-impaired EPC functions, inhibited high glucose-induced EPC senescence and reduced H2O2 production. Nude mice received human EPCs treated with IFR in high glucose medium showed a significant improvement in blood flow recovery in ischemic limb compared to those without IFR therapy. IFR therapy promoted blood flow recovery and new vessel formation in STZ-induced diabetic mice. Conclusions Administration of IFR therapy promoted collateral flow recovery and new vessel formation in STZ

  9. Normal serum matrix metalloproteinase-3 levels can be used to predict clinical remission and normal physical function in patients with rheumatoid arthritis.

    Science.gov (United States)

    Hattori, Yosuke; Kida, Daihei; Kaneko, Atsushi

    2017-09-22

    This study aimed to evaluate whether normal serum matrix metalloproteinase-3 (MMP-3) levels can be used to predict clinical remission and normal physical function at a single time point when treating patients with rheumatoid arthritis (RA) in daily practice settings. Subjects were all 1321 RA patients who were treated at our hospital. The accuracy of serum MMP-3 levels was larger than those of C-reactive protein (CRP) levels for predicting clinical remission [Simplified Disease Activity Index (SDAI) ≤ 3.3], normal function [Disability Index of the Health Assessment Questionnaire (HAQ-DI) ≤ 0.5], and both in clinical remission and with normal function (clinical remission + normal function) using receiver operating characteristic curve analysis. Serum MMP-3 levels were significantly correlated with CRP levels [r 0.229 (men), r 0.476 (women)] using Pearson's correlation coefficients. Among patients with normal CRP levels (n = 807), the percentage of patients in clinical remission, with normal function, and with clinical remission + normal function having normal serum MMP-3 levels was significantly higher than those with abnormal serum MMP-3 levels. In addition, among patients with the 28-point count Disease Activity Score-CRP (DAS28-CRP) remission (DAS28-CRP normal function, and with clinical remission + normal function having normal serum MMP-3 levels was significantly higher than those with abnormal serum MMP-3 levels. Our findings suggest that normal serum MMP-3 levels, in combination with CRP levels or disease activity, are useful for predicting clinical remission and normal physical function in patients with RA.

  10. Pharmacokinetic-Pharmacodynamic Model for the Effect of l-Arginine on Endothelial Function in Patients with Moderately Severe Falciparum Malaria

    Science.gov (United States)

    Brussee, Janneke M.; Yeo, Tsin W.; Lampah, Daniel A.; Anstey, Nicholas M.

    2015-01-01

    Impaired organ perfusion in severe falciparum malaria arises from microvascular sequestration of parasitized cells and endothelial dysfunction. Endothelial dysfunction in malaria is secondary to impaired nitric oxide (NO) bioavailability, in part due to decreased plasma concentrations of l-arginine, the substrate for endothelial cell NO synthase. We quantified the time course of the effects of adjunctive l-arginine treatment on endothelial function in 73 patients with moderately severe falciparum malaria derived from previous studies. Three groups of 10 different patients received 3 g, 6 g, or 12 g of l-arginine as a half-hour infusion. The remaining 43 received saline placebo. A pharmacokinetic-pharmacodynamic (PKPD) model was developed to describe the time course of changes in exhaled NO concentrations and reactive hyperemia-peripheral arterial tonometry (RH-PAT) index values describing endothelial function and then used to explore optimal dosing regimens for l-arginine. A PK model describing arginine concentrations in patients with moderately severe malaria was extended with two pharmacodynamic biomeasures, the intermediary biochemical step (NO production) and endothelial function (RH-PAT index). A linear model described the relationship between arginine concentrations and exhaled NO. NO concentrations were linearly related to RH-PAT index. Simulations of dosing schedules using this PKPD model predicted that the time within therapeutic range would increase with increasing arginine dose. However, simulations demonstrated that regimens of continuous infusion over longer periods would prolong the time within the therapeutic range even more. The optimal dosing regimen for l-arginine is likely to be administration schedule dependent. Further studies are necessary to characterize the effects of such continuous infusions of l-arginine on NO and microvascular reactivity in severe malaria. PMID:26482311

  11. Functional characterization of S100A8 and S100A9 in altering monolayer permeability of human umbilical endothelial cells.

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    Liqun Wang

    Full Text Available S100A8, S100A9 and S100A8/A9 complexes have been known as important endogenous damage-associated molecular pattern (DAMP proteins. But the pathophysiological roles of S100A8, S100A9 and S100A8/A9 in cardiovascular diseases are incompletely explained. In this present study, the effects of homo S100A8, S100A9 and their hetero-complex S100A8/A9 on endothelial barrier function were tested respectively in cultured human umbilical venous endothelial cells (HUVECs. The involvement of TLR4 and RAGE were observed by using inhibitor of TLR4 and blocking antibody of RAGE. The clarification of different MAPK subtypes in S100A8/A9-induced endothelial response was implemented by using specific inhibitors. The calcium-dependency was detected in the absence of Ca2+ or in the presence of gradient-dose Ca2+. The results showed that S100A8, S100A9 and S100A8/A9 could induce F-actin and ZO-1 disorganization in HUVECs and evoked the increases of HUVEC monolayer permeability in a dose- and time-dependent manner. The effects of S100A8, S100A9 and S100A8/A9 on endothelial barrier function depended on the activation of p38 and ERK1/2 signal pathways through receptors TLR4 and RAGE. Most importantly, we revealed the preference of S100A8 on TLR4 and S100A9 on RAGE in HUVECs. The results also showed the calcium dependency in S100A8- and S100A9-evoked endothelial response, indicating that calcium dependency on formation of S100A8 or A9 dimmers might be the prerequisite for this endothelial functional alteration.

  12. A 12-week after-school physical activity programme improves endothelial cell function in overweight and obese children: a randomised controlled study

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    Park Jong-Hwan

    2012-07-01

    Full Text Available Abstract Background Endothelial dysfunction is associated with childhood obesity and is closely linked to the amount and function of endothelial progenitor cells. However, it remains unclear whether endothelial progenitor cells increase with after-school exercise in overweight and obese children. The purpose of this study was to investigate the effects of an after-school exercise programme on endothelial cell function in overweight and obese children. Methods A total of 29 overweight/obese children (12.2 ± 0.1 years were randomly divided into control (i.e. no after-school exercise, n = 14 and after-school exercise (n = 15 groups. The 12-week after-school exercise intervention consisted of 3 days of combined aerobic and resistance exercise per week. Each 80-minute exercise programme included 10 minutes of warm-up and 10 minutes of cool-down after school. CD34+ (a cell surface marker on hematopoietic stem cells, CD133+ (a cell surface marker on hematopoietic progenitor cells and CD34+/CD133+ (considered as endothelial progenitor cells were measured at baseline and after 12 weeks using flow cytometry. Results Increased percentages of CD34+, CD133+ and CD34+/CD133+ cells were observed in the after-school exercise group (p = 0.018; p = 0.001; p = 0.002, respectively compared with the control group. Carotid intima-media thickness decreased after 12 weeks in the after-school exercise group (p = 0.020 compared with the control group. Conclusions This study provides preliminary evidence that a combined after-school exercise programme may represent an effective intervention strategy for improving vascular repair and endothelial cell function, leading to improved cardiovascular health in overweight and obese children. Trial registration Current Controlled Trials ISRCTN19037201

  13. Expression and function of receptors for advanced glycation end products in bovine corneal endothelial cells.

    Science.gov (United States)

    Kaji, Yuichi; Amano, Shiro; Usui, Tomohiko; Oshika, Tetsuro; Yamashiro, Kenji; Ishida, Susumu; Suzuki, Kaori; Tanaka, Sumiyoshi; Adamis, Anthony P; Nagai, Ryoji; Horiuchi, Seiko

    2003-02-01

    The corneal endothelium is a target of the aging process. This study was undertaken to reveal the relationship between corneal endothelial cell (CEC) death and the accumulation of advanced glycation end products (AGEs), by investigating the possible mechanism of accumulation of AGE in CECs and its effects on CEC death. First, the in vivo expression of the receptor was investigated for AGE (RAGE) and galectin-3, both receptors for AGE, at both the mRNA and protein levels. Second, AGEs were added to the culture media of the cultured CECs, and the uptake of AGEs, the generation of reactive oxygen species, and the induction of apoptosis were investigated. Immunohistochemistry and RT-PCR demonstrated that both RAGE and galectin-3 were expressed in bovine CECs. After administration of AGE-modified bovine serum albumin to the culture medium, uptake of AGE was observed in the cytoplasm of the cultured bovine CECs. In addition, with increasing concentration of AGEs, the generation of reactive oxygen and the number of apoptotic cells also increased. These results show that the accumulation of AGEs in CECs induced apoptosis, in part, by increasing cellular oxidative stress. The accumulation of AGEs in the CECs of elderly patients may be involved in the loss of CECs during the aging process.

  14. Characterization Theorems for Generalized Functionals of Discrete-Time Normal Martingale

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    Caishi Wang

    2015-01-01

    Full Text Available We aim at characterizing generalized functionals of discrete-time normal martingales. Let M=(Mnn∈N be a discrete-time normal martingale that has the chaotic representation property. We first construct testing and generalized functionals of M with an appropriate orthonormal basis for M’s square integrable functionals. Then we introduce a transform, called the Fock transform, for these functionals and characterize them via the transform. Several characterization theorems are established. Finally we give some applications of these characterization theorems. Our results show that generalized functionals of discrete-time normal martingales can be characterized only by growth condition, which contrasts sharply with the case of some continuous-time processes (e.g., Brownian motion, where both growth condition and analyticity condition are needed to characterize generalized functionals of those continuous-time processes.

  15. Vascular Endothelial Growth Factor Is Associated with the Morphologic and Functional Parameters in Patients with Hypertrophic Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Radek Pudil

    2015-01-01

    Full Text Available Background. Hypertrophic cardiomyopathy (HCM is mostly autosomal dominant disease of the myocardium, which is characterized by myocardial hypertrophy. Vascular endothelial growth factor (VEGF is involved in myocyte function, growth, and survival. The aim of study was to analyze the clinical significance of VEGF in structural and functional changes in patient with HCM. Methods. In a group of 21 patients with nonobstructive HCM, we assessed serum VEGF and analyzed its association with morphological and functional parameters. Compared to healthy controls, serum VEGF was increased: 199 (IQR: 120.4–260.8 ng/L versus 20 (IQR: 14.8–37.7 ng/L, P<0.001. VEGF levels were associated with left atrium diameter (r=0.51, P=0.01, left ventricle ejection fraction (r=-0.56, P=0.01, fractional shortening (r=-0.54, P=0.02, left ventricular mass (r=0.61, P=0.03, LV mass index (r=0.46, P=0.04, vena cava inferior diameter (r=0.65, P=0.01, and peak gradient of tricuspid regurgitation (r=0.46, P=0.03. Conclusions. Increased VEGF level is associated with structural and functional parameters in patients with HCM and serves as a potential tool for diagnostic process of these patients.

  16. Dual delivery of hepatocyte and vascular endothelial growth factors via a protease-degradable hydrogel improves cardiac function in rats.

    Directory of Open Access Journals (Sweden)

    Apoorva S Salimath

    Full Text Available Acute myocardial infarction (MI caused by ischemia and reperfusion (IR is the most common cause of cardiac dysfunction due to local cell death and a temporally regulated inflammatory response. Current therapeutics are limited by delivery vehicles that do not address spatial and temporal aspects of healing. The aim of this study was to engineer biotherapeutic delivery materials to harness endogenous cell repair to enhance myocardial repair and function. We have previously engineered poly(ethylene glycol (PEG-based hydrogels to present cell adhesive motifs and deliver VEGF to promote vascularization in vivo. In the current study, bioactive hydrogels with a protease-degradable crosslinker were loaded with hepatocyte and vascular endothelial growth factors (HGF and VEGF, respectively and delivered to the infarcted myocardium of rats. Release of both growth factors was accelerated in the presence of collagenase due to hydrogel degradation. When delivered to the border zones following ischemia-reperfusion injury, there was no acute effect on cardiac function as measured by echocardiography. Over time there was a significant increase in angiogenesis, stem cell recruitment, and a decrease in fibrosis in the dual growth factor delivery group that was significant compared with single growth factor therapy. This led to an improvement in chronic function as measured by both invasive hemodynamics and echocardiography. These data demonstrate that dual growth factor release of HGF and VEGF from a bioactive hydrogel has the capacity to significantly improve cardiac remodeling and function following IR injury.

  17. Effect of Trimetazidine Dihydrochloride Tablets adjuvant therapy on inflammatory reaction, oxidative stress, vascular endothelial function and myocardial function in patients with coronary heart disease complicated with heart failure

    Directory of Open Access Journals (Sweden)

    Cai-Wen Wei

    2017-11-01

    Full Text Available Objective: To investigate the effects of Trimetazidine Dihydrochloride Tablets on inflammatory reaction, oxidative stress, vascular endothelial function and myocardial function in patients with coronary heart disease complicated with heart failure. Methods: A total of 98 patients with coronary heart disease and heart failure who met the criteria of the study were selected as the subjects, based on the random data table they were divided into the control group (n=49 and observation group (n=49, the patients in the control group were treated with Metoprolol Tartrate Sustained-release Tablets treatment, and the patients in the observation group were treated with Metoprolol Tartrate Sustained-release Tablets combined with Trimetazidine Dihydrochloride Tablets, the levels of inflammatory reaction, oxidative stress, vascular endothelial function and myocardial function indexes were compared between the two groups before and after treatment. Results: The difference of the CRP, TNF-α, MDA, SOD, NO, ET-1, LVEF, LVEDD and LVESD levels in the two groups before treatment were not statistically significant; Compared with the levels of the two groups before treatment, the two groups of CRP, TNF-α, MDA, ET-1, LVEDD and LVESD levels after treatment were significantly decreased, and the level of the observation group after treatment was significantly lower than those levels in the control group, the difference was statistically significant; The levels of SOD, NO and LVEF of the two groups after treatment were significantly higher than those in the same group before treatment, and the observation group levels [(88.09±7.51 U/ ml, (72.58±14.64 mol/L, (48.34±5.09% ] were significantly higher than the control group [(79.44±7.27 U/ml, (61.89±11.06 mol/L, (44.19±4.58%], the difference was statistically significant. Conclusion: Trimetazidine Dihydrochloride Tablets in the treatment of coronary heart disease with heart failure can effectively inhibit the release

  18. Plant stanols do not restore endothelial function in pre-pubertal children with familial hypercholesterolemia despite reduction of low-density lipoprotein cholesterol levels

    NARCIS (Netherlands)

    Jakulj, Lily; Vissers, Maud N.; Rodenburg, Jessica; Wiegman, Albert; Trip, Mieke D.; Kastelein, John J. P.

    2006-01-01

    OBJECTIVE: To examine the effect of plant stanols on lipids and endothelial function in pre-pubertal children with familial hypercholesterolemia (FH). STUDY DESIGN: Children with FH (n=42), aged 7-12 years, were enrolled in a double-blind crossover trial, in which they consumed 500 mL of a low-fat

  19. Effect of intensive lipid-lowering treatment compared to moderate lipid-lowering treatment with rosuvastatin on endothelial function in high risk patients

    DEFF Research Database (Denmark)

    Egede, Rasmus; Jensen, Lisette Okkels; Hansen, Henrik Steen

    2011-01-01

    on the endothelial function evaluated with endothelium-dependent and endothelium-independent flow-mediated dilatation (FMD). METHODS: 87 Statin-naive patients with ST-segment elevation myocardial infarction (STEMI) were randomized to 5mg or 40mg rosuvastatin. The FMD was assessed at baseline, 6months and after 12...

  20. Associations of sedentary time patterns and TV viewing time with inflammatory and endothelial function biomarkers in children

    Science.gov (United States)

    Gabel, L.; Ridgers, N. D.; Della Gatta, P. A.; Arundell, L.; Cerin, E.; Robinson, S.; Daly, R. M.; Dunstan, D. W.

    2015-01-01

    Summary Objective Investigate associations of TV viewing time and accelerometry‐derived sedentary time with inflammatory and endothelial function biomarkers in children. Methods Cross‐sectional analysis of 164 7–10‐year‐old children. TV viewing time was assessed by parental proxy report and total and patterns of sedentary time accumulation (e.g. prolonged bouts) were assessed by accelerometry. C‐reactive protein (CRP), homeostasis model assessment of insulin resistance, interleukin‐2, ‐6, ‐8, ‐10, tumour necrosis factor alpha, adiponectin, resistin, brain‐derived neurotrophic factor, soluble intercellular and vascular adhesion molecule 1, plasminogen activator inhibitor 1 and soluble E‐selectin were assessed. Generalised linear models assessed the associations of TV viewing and sedentary time with biomarkers, adjusting for sex, waist circumference, moderate‐ to vigorous‐intensity physical activity and diet density. Results Each additional h week−1 of TV viewing was associated with 4.4% (95% CI: 2.1, 6.7) greater CRP and 0.6% (0.2, 1.0) greater sVCAM‐1 in the fully adjusted model. The association between frequency and duration of 5–10 min bouts of sedentary time and CRP was positive after adjustment for sex and waist circumference but attenuated after adjustment for diet density. Conclusions This study suggests that TV viewing was unfavourably associated with several markers of inflammation and endothelial dysfunction. The detrimental association between 5 and 10 min bouts of sedentary time and CRP approached significance, suggesting that further research with a stronger study design (longitudinal and/or experimental) is needed to better understand how the accumulation of sedentary time early in life may influence short and longer term health. PMID:26097139

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

    Science.gov (United States)

    Huffman, Mark D; Khalil, Anita; Osmond, Clive; Fall, Caroline H D; Tandon, Nikhil; Lakshmy, Ramakrishnan; Ramji, Siddharth; Gera, Tarun; Prabhakaran, Poornima; Dey Biswas, S K; Reddy, K Srinath; Bhargava, Santosh K; Sachdev, Harshpal S; Prabhakaran, Dorairaj

    2015-12-01

    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. 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. 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. 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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Effects of cryopreservation on excretory function, cellular adhesion molecules and vessel lumen formation in human umbilical vein endothelial cells.

    Science.gov (United States)

    Cai, Guoping; Lai, Binbin; Hong, Huaxing; Lin, Peng; Chen, Weifu; Zhu, Zhong; Chen, Haixiao

    2017-07-01

    Cryopreservation is widely used in regenerative medicine for tissue preservation. In the present study, the effects of cryopreservation on excretory function, cellular adhesion molecules and vessel lumen formation in human umbilical vein endothelial cells (HUVECs) were investigated. After 0, 4, 8, 12 or 24 weeks of cryopreservation in liquid nitrogen, the HUVECs were thawed. The excretory functions markers (endothelin‑1, prostaglandin E1, von Willebrand factor and nitric oxide) of HUVECs were measured by ELISA assay. The expression of intercellular adhesion molecule‑1 (ICAM‑1) in HUVECs was analyzed using flow cytometry. An angiogenesis assay was used to determine the angiogeneic capabilities of the thawed HUVECs. The results demonstrated that cryopreserved/thawed and recultivated HUVECs were unsuitable for tissue‑engineered microvascular construction. Specifically, the excretory function of the cells was significantly decreased in the post‑cryopreserved HUVECs at 24 weeks. In addition, the level of ICAM‑1 in HUVECs was significantly upregulated from the fourth week of cryopreservation. Furthermore, the tube‑like structure‑forming potential was weakened with increasing cryopreservation duration, and the numbers of lumen and the length of the pipeline were decreased in the thawed HUVECs, in a time‑dependent manner. In conclusion, the results of the present study revealed that prolonged cryopreservation may lead to HUVEC dysfunction and did not create stable cell lines for tissue‑engineered microvascular construction.

  5. Endothelial cell-derived matrix promotes the metabolic functional maturation of hepatocyte via integrin-Src signalling.

    Science.gov (United States)

    Guo, Xinyue; Li, Weihong; Ma, Minghui; Lu, Xin; Zhang, Haiyan

    2017-11-01

    The extracellular matrix (ECM) microenvironment is involved in the regulation of hepatocyte phenotype and function. Recently, the cell-derived extracellular matrix has been proposed to represent the bioactive and biocompatible materials of the native ECM. Here, we show that the endothelial cell-derived matrix (EC matrix) promotes the metabolic maturation of human adipose stem cell-derived hepatocyte-like cells (hASC-HLCs) through the activation of the transcription factor forkhead box protein A2 (FOXA2) and the nuclear receptors hepatocyte nuclear factor 4 alpha (HNF4α) and pregnane X receptor (PXR). Reducing the fibronectin content in the EC matrix or silencing the expression of α5 integrin in the hASC-HLCs inhibited the effect of the EC matrix on Src phosphorylation and hepatocyte maturation. The inhibition of Src phosphorylation using the inhibitor PP2 or silencing the expression of Src in hASC-HLCs also attenuated the up-regulation of the metabolic function of hASC-HLCs in a nuclear receptor-dependent manner. These data elucidate integrin-Src signalling linking the extrinsic EC matrix signals and metabolic functional maturation of hepatocyte. This study provides a model for studying the interaction between hepatocytes and non-parenchymal cell-derived matrix. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  6. The RNA-binding protein quaking maintains endothelial barrier function and affects VE-cadherin and β-catenin protein expression.

    Science.gov (United States)

    de Bruin, Ruben G; van der Veer, Eric P; Prins, Jurriën; Lee, Dae Hyun; Dane, Martijn J C; Zhang, Huayu; Roeten, Marko K; Bijkerk, Roel; de Boer, Hetty C; Rabelink, Ton J; van Zonneveld, Anton Jan; van Gils, Janine M

    2016-02-24

    Proper regulation of endothelial cell-cell contacts is essential for physiological functioning of the endothelium. Interendothelial junctions are actively involved in the control of vascular leakage, leukocyte diapedesis, and the initiation and progression of angiogenesis. We found that the RNA-binding protein quaking is highly expressed by endothelial cells, and that its expression was augmented by prolonged culture under laminar flow and the transcription factor KLF2 binding to the promoter. Moreover, we demonstrated that quaking directly binds to the mRNA of VE-cadherin and β-catenin and can induce mRNA translation mediated by the 3'UTR of these genes. Reduced quaking levels attenuated VE-cadherin and β-catenin expression and endothelial barrier function in vitro and resulted in increased bradykinin-induced vascular leakage in vivo. Taken together, we report that quaking is essential in maintaining endothelial barrier function. Our results provide novel insight into the importance of post-transcriptional regulation in controlling vascular integrity.

  7. Endothelial Function Assessed by Peripheral Arterial Tonometry is not related to Cardiovascular Risk Score in Healthy Subjects

    Directory of Open Access Journals (Sweden)

    Ylfa Run Sigurdardottir

    2016-01-01

    Endothelial dysfunction, measured by PAT, was not associated with an increased 10-year risk of developing CVD. The relation between endothelial dysfunction and established CV risk factors was limited. Further clinical end point studies are needed to fully comprehend the diagnostic and predictive value of PAT measurements in healthy subjects.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  9. Chronic Lymphocytic Leukemia B-Cell Normal Cellular Counterpart: Clues From a Functional Perspective.

    Science.gov (United States)

    Darwiche, Walaa; Gubler, Brigitte; Marolleau, Jean-Pierre; Ghamlouch, Hussein

    2018-01-01

    Chronic lymphocytic leukemia (CLL) is characterized by the clonal expansion of small mature-looking CD19+ CD23+ CD5+ B-cells that accumulate in the blood, bone marrow, and lymphoid organs. To date, no consensus has been reached concerning the normal cellular counterpart of CLL B-cells and several B-cell types have been proposed. CLL B-cells have remarkable phenotypic and gene expression profile homogeneity. In recent years, the molecular and cellular biology of CLL has been enriched by seminal insights that are leading to a better understanding of the natural history of the disease. Immunophenotypic and molecular approaches (including immunoglobulin heavy-chain variable gene mutational status, transcriptional and epigenetic profiling) comparing the normal B-cell subset and CLL B-cells provide some new insights into the normal cellular counterpart. Functional characteristics (including activation requirements and propensity for plasma cell differentiation) of CLL B-cells have now been investigated for 50 years. B-cell subsets differ substantially in terms of their functional features. Analysis of shared functional characteristics may reveal similarities between normal B-cell subsets and CLL B-cells, allowing speculative assignment of a normal cellular counterpart for CLL B-cells. In this review, we summarize current data regarding peripheral B-cell differentiation and human B-cell subsets and suggest possibilities for a normal cellular counterpart based on the functional characteristics of CLL B-cells. However, a definitive normal cellular counterpart cannot be attributed on the basis of the available data. We discuss the functional characteristics required for a cell to be logically considered to be the normal counterpart of CLL B-cells.

  10. Ratio of serum levels of AGEs to soluble form of RAGE is a predictor of endothelial function.

    Science.gov (United States)

    Kajikawa, Masato; Nakashima, Ayumu; Fujimura, Noritaka; Maruhashi, Tatsuya; Iwamoto, Yumiko; Iwamoto, Akimichi; Matsumoto, Takeshi; Oda, Nozomu; Hidaka, Takayuki; Kihara, Yasuki; Chayama, Kazuaki; Goto, Chikara; Aibara, Yoshiki; Noma, Kensuke; Takeuchi, Masayoshi; Matsui, Takanori; Yamagishi, Sho-Ichi; Higashi, Yukihito

    2015-01-01

    Advanced glycation end products (AGEs) and their specific receptor, the receptor for AGEs (RAGE), play an important role in atherosclerosis. Recently, a soluble form of RAGE (sRAGE) has been identified in human serum. However, the role of sRAGE in cardiovascular disease is still controversial. There is no information on the association between simultaneous measurements of AGEs and sRAGE and vascular function. In this study, we evaluated the associations between serum levels of AGEs and sRAGE, ratio of AGEs to sRAGE, and vascular function. We measured serum levels of AGEs and sRAGE and assessed vascular function by measurement of flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation in 110 subjects who underwent health examinations. Multivariate regression analyses were performed to identify factors associated with vascular function. Univariate regression analysis revealed that FMD correlated with age, BMI, systolic blood pressure, diastolic blood pressure, heart rate, triglycerides, HDL cholesterol, glucose, smoking pack-years, nitroglycerine-induced vasodilation, serum levels of AGEs and sRAGE, and ratio of AGEs to sRAGE. Multivariate analysis revealed that the ratio of AGEs to sRAGE remained an independent predictor of FMD, while serum level of AGEs alone or sRAGE alone was not associated with FMD. These findings suggest that sRAGE may have a counterregulatory mechanism that is activated to counteract the vasotoxic effect of the AGE-RAGE axis. The ratio of AGEs to sRAGE may be a new chemical biomarker of endothelial function. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  11. Age related vascular endothelial function following lifelong sedentariness: positive impact of cardiovascular conditioning without further improvement following low frequency high intensity interval training

    OpenAIRE

    Grace, Fergal M.; Herbert, Peter; Ratcliffe, John W.; New, Karl J.; Baker, Julien S.; Sculthorpe, Nicholas F.

    2015-01-01

    Abstract Aging is associated with diffuse impairments in vascular endothelial function and traditional aerobic exercise is known to ameliorate these changes. High intensity interval training (HIIT) is effective at improving vascular function in aging men with existing disease, but its effectiveness remains to be demonstrated in otherwise healthy sedentary aging. However, the frequency of commonly used HIIT protocols may be poorly tolerated in older cohorts. Therefore, the present study invest...

  12. Vascular endothelial growth factor promotes anatomical and functional recovery of injured peripheral nerves in the avascular cornea.

    Science.gov (United States)

    Pan, Zan; Fukuoka, Shima; Karagianni, Natalia; Guaiquil, Victor H; Rosenblatt, Mark I

    2013-07-01

    Peripheral nerve injury is a major neurological disorder that can cause severe motor and sensory dysfunction. Neurogenic effects of vascular endothelial growth factor (VEGF) have been found in the central nervous system, and we examined whether VEGF could promote anatomical and functional recovery of peripheral nerves after injury using an avascular corneal nerve injury model. We found that VEGF enhanced neurite elongation in isolated trigeminal ganglion neurons in a dose-dependent manner. This effect was suppressed by neutralizing antibodies for VEGF receptor (VEGFR) 1 and 2 or neuropilin receptor 1 or by VEGFR2 inhibitors (SU 1498 and Ki 8751). In vivo, mice receiving sustained VEGF via implanted pellets showed increased corneal nerve regeneration after superficial injury compared with those receiving vehicle. VEGF injected subconjunctivally at the time of injury accelerated reinnervation, the recovery of mechanosensation, and epithelial wound healing. Endogenous VEGF expression was up-regulated in the corneal epithelium and stroma after wounding. Thus, VEGF can mediate peripheral neuron growth but requires the activation of multiple VEGF receptor types. In addition, VEGF can accelerate the return of sensory and trophic functions of damaged peripheral nerves. Wounding induces the expression of VEFG, which may modulate physiological nerve repair.

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

    DEFF Research Database (Denmark)

    Chennupati, Ramesh; Meens, Merlijn J P M T; Marion, Vincent

    2014-01-01

    AIM: 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. METHODS...... 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...

  14. Green coffee polyphenols do not attenuate features of the metabolic syndrome and improve endothelial function in mice fed a high fat diet.

    Science.gov (United States)

    Li Kwok Cheong, J D; Croft, K D; Henry, P D; Matthews, V; Hodgson, J M; Ward, N C

    2014-10-01

    We have investigated the effects of the major polyphenol in coffee, chlorogenic acid (CGA), on obesity, glucose intolerance, insulin resistance, systemic oxidative stress and endothelial dysfunction in a mouse model of the metabolic syndrome. Thirty C57BL6 mice were randomly divided into (n=10/group) (i) normal diet (ND), (ii) high fat diet (HFD), or (iii) high fat diet supplemented with 0.5% w/w green coffee bean extract (GCE) rich in chlorogenic acid (HFD+GCE). The high fat diet consisted of 28% fat and all animals were maintained on their diets for 12 weeks. The mice fed a HFD and HFD+GCE displayed symptoms of the metabolic syndrome compared to their normal fed counterparts, although no endothelial dysfunction was detected in the abdominal aortas after 12 weeks. GCE did not attenuate HFD-induced obesity, glucose intolerance, insulin resistance or systemic oxidative stress. Furthermore, GCE did not protect against ex vivo oxidant (hypochlorous acid)-induced endothelial dysfunction. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Validation of MCDS by comparison of predicted with experimental velocity distribution functions in rarefied normal shocks

    Science.gov (United States)

    Pham-Van-diep, Gerald C.; Erwin, Daniel A.

    1989-01-01

    Velocity distribution functions in normal shock waves in argon and helium are calculated using Monte Carlo direct simulation. These are compared with experimental results for argon at M = 7.18 and for helium at M = 1.59 and 20. For both argon and helium, the variable-hard-sphere (VHS) model is used for the elastic scattering cross section, with the velocity dependence derived from a viscosity-temperature power-law relationship in the way normally used by Bird (1976).

  16. Renal function maturation in children: is normalization to surface area valid?

    International Nuclear Information System (INIS)

    Rutland, M.D.; Hassan, I.M.; Que, L.

    1999-01-01

    Full text: Gamma camera DTPA renograms were analysed to measure renal function by the rate at which the kidneys took up tracer from the blood. This was expressed either directly as the fractional uptake rate (FUR), which is not related to body size, or it was converted to a camera-based GFR by the formula GFR blood volume x FUR, and this GFR was normalized to a body surface area of 1.73 m2. Most of the patients studied had one completely normal kidney, and one kidney with reflux but normal function and no large scars. The completely normal kidneys contributed, on average, 50% of the total renal function. The results were considered in age bands, to display the effect of age on renal function. The camera-GFR measurements showed the conventional results of poor renal function in early childhood, with a slow rise to near-adult values by the age of 2 years, and somewhat low values throughout childhood. The uptake values showed a different pattern, with renal function rising to adult equivalent values by the age of 4 months, and with children having better renal function than adults throughout most of their childhood. The standard deviations expressed as coefficients of variation (CV) were smaller for the FUR technique than the GFR (Wilcoxon rank test, P < 0.01). These results resemble recent published measurements of absolute DMSA uptake, which are also unrelated to body size and show early renal maturation. The results also suggest that the reason children have lower serum creatinine levels than adults is that they have better renal function. If this were confirmed, it would raise doubts about the usefulness of normalizing renal function to body surface area in children

  17. The Application of Normal Stress Reduction Function in Tilt Tests for Different Block Shapes

    Science.gov (United States)

    Kim, Dong Hyun; Gratchev, Ivan; Hein, Maw; Balasubramaniam, Arumugam

    2016-08-01

    This paper focuses on the influence of the shapes of rock cores, which control the sliding or toppling behaviours in tilt tests for the estimation of rock joint roughness coefficients (JRC). When the JRC values are estimated by performing tilt tests, the values are directly proportional to the basic friction of the rock material and the applied normal stress on the sliding planes. Normal stress obviously varies with the shape of the sliding block, and the basic friction angle is also affected by the sample shapes in tilt tests. In this study, the shapes of core blocks are classified into three representative shapes and those are created using plaster. Using the various shaped artificial cores, a set of tilt tests is carried out to identify the shape influences on the normal stress and the basic friction angle in tilt tests. The test results propose a normal stress reduction function to estimate the normal stress for tilt tests according to the sample shapes based on Barton's empirical equation. The proposed normal stress reduction functions are verified by tilt tests using artificial plaster joints and real rock joint sets. The plaster joint sets are well matched and cast in detailed printed moulds using a 3D printing technique. With the application of the functions, the obtained JRC values from the tilt tests using the plaster samples and the natural rock samples are distributed within a reasonable JRC range when compared with the measured values.

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

    Science.gov (United States)

    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.

  19. Role of oxidants/inflammation in declining renal function in chronic kidney disease and normal aging.

    Science.gov (United States)

    Vlassara, Helen; Torreggiani, Massimo; Post, James B; Zheng, Feng; Uribarri, Jaime; Striker, Gary E

    2009-12-01

    Oxidant stress (OS) and inflammation increase in normal aging and in chronic kidney disease (CKD), as observed in human and animal studies. In cross-sectional studies of the US population, these changes are associated with a decrease in renal function, which is exhibited by a significant proportion of the population. However, since many normal adults have intact renal function, and longitudinal studies show that some persons maintain normal renal function with age, the link between OS, inflammation, and renal decline is not clear. In aging mice, greater oxidant intake is associated with increased age-related CKD and mortality, which suggests that interventions that reduce OS and inflammation may be beneficial for older individuals. Both OS and inflammation can be readily lowered in normal