scholarly journals Impact of Rosuvastatin Treatment on HDL-Induced PKC-βII and eNOS Phosphorylation in Endothelial Cells and Its Relation to Flow-Mediated Dilatation in Patients with Chronic Heart Failure

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Ephraim B. Winzer ◽  
Pauline Gaida ◽  
Robert Höllriegel ◽  
Tina Fischer ◽  
Axel Linke ◽  
...  
Keyword(s):  
Heart Failure ◽  
Endothelial Cells ◽  
Chronic Heart Failure ◽  
Endothelial Function ◽  
No Production ◽  
Treatment Cessation ◽  
Aortic Endothelial Cells ◽  
Enos Phosphorylation ◽  
Flow Mediated Dilatation ◽  
The Impact

Background. Endothelial function is impaired in chronic heart failure (CHF). Statins upregulate endothelial NO synthase (eNOS) and improve endothelial function. Recent studies demonstrated that HDL stimulates NO production due to eNOS phosphorylation at Ser1177, dephosphorylation at Thr495, and diminished phosphorylation of PKC-βII at Ser660. The aim of this study was to elucidate the impact of rosuvastatin on HDL mediated eNOS and PKC-βII phosphorylation and its relation to endothelial function.Methods. 18 CHF patients were randomized to 12 weeks of rosuvastatin or placebo. At baseline, 12 weeks, and 4 weeks after treatment cessation we determined lipid levels and isolated HDL. Human aortic endothelial cells (HAEC) were incubated with isolated HDL and phosphorylation of eNOS and PKC-βII was evaluated. Flow-mediated dilatation (FMD) was measured at the radial artery.Results. Rosuvastatin improved FMD significantly. This effect was blunted after treatment cessation. LDL plasma levels were reduced after rosuvastatin treatment whereas drug withdrawal resulted in significant increase. HDL levels remained unaffected. Incubation of HAEC with HDL had no impact on phosphorylation of eNOS or PKC-βII.Conclusion. HDL mediated eNOS and PKC-βII phosphorylation levels in endothelial cells do not change with rosuvastatin in CHF patients and do not mediate the marked improvement in endothelial function.

scholarly journals Cadmium reduces nitric oxide production by impairing phosphorylation of endothelial nitric oxide synthase

2008 ◽  
Vol 86 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Syamantak Majumder ◽  
Ajit Muley ◽  
Gopi Krishna Kolluru ◽  
Samir Saurabh ◽  
K. P. Tamilarasan ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Endothelial Function ◽  
Egg Yolk ◽  
Cellular Migration ◽  
No Production ◽  
Enos Phosphorylation ◽  
Low Levels ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Cadmium (Cd) perturbs vascular health and interferes with endothelial function. However, the effects of exposing endothelial cells to low doses of Cd on the production of nitric oxide (NO) are largely unknown. The objective of the present study was to evaluate these effects by using low levels of CdCl2 concentrations, ranging from 10 to 1000 nmol/L. Cd perturbations in endothelial function were studied by employing wound-healing and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays. The results suggest that a CdCl2 concentration of 100 nmol/L maximally attenuated NO production, cellular migration, and energy metabolism in endothelial cells. An egg yolk angiogenesis model was employed to study the effect of Cd exposure on angiogenesis. The results demonstrate that NO supplementation restored Cd-attenuated angiogenesis. Immunofluorescence, Western blot, and immuno-detection studies showed that low levels of Cd inhibit NO production in endothelial cells by blocking eNOS phosphorylation, which is possibly linked to processes involving endothelial function and dysfunction, including angiogenesis.

Deferiprone increases endothelial nitric oxide synthase phosphorylation and nitric oxide production

2018 ◽  
Vol 96 (9) ◽  
pp. 879-885 ◽  
Author(s):  
Thanaporn Sriwantana ◽  
Pornpun Vivithanaporn ◽  
Kittiphong Paiboonsukwong ◽  
Krit Rattanawonsakul ◽  
Sirada Srihirun ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Endothelial Cells ◽  
Endothelial Function ◽  
Healthy Subjects ◽  
Iron Chelation ◽  
No Production ◽  
Hemoglobin E ◽  
Enos Phosphorylation

Iron chelation can improve endothelial function. However, effect on endothelial function of deferiprone has not been reported. We hypothesized deferiprone could promote nitric oxide (NO) production in endothelial cells. We studied effects of deferiprone on blood nitrite and blood pressure after single oral dose (25 mg/kg) in healthy subjects and hemoglobin E/β-thalassemia patients. Further, effects of deferiprone on NO production and endothelial NO synthase (eNOS) phosphorylation in primary human pulmonary artery endothelial cells (HPAEC) were investigated in vitro. Blood nitrite levels were higher in patients with deferiprone therapy than those without deferiprone (P = 0.023, n = 16 each). Deferiprone increased nitrite in plasma and whole blood of healthy subjects (P = 0.002 and 0.044) and thalassemia patients (P = 0.003 and 0.046) at time 180 min (n = 20 each). Asymptomatic reduction in diastolic blood pressure (P = 0.005) and increase in heart rate (P = 0.009) were observed in healthy subjects, but not in thalassemia patients. In HPAEC, deferiprone increased cellular nitrite and phospho-eNOS (Ser1177) (P = 0.012 and 0.035, n = 6) without alteration in total eNOS protein and mRNA. We conclude that deferiprone can induce NO production by enhancing eNOS phosphorylation in endothelial cells.

scholarly journals Exenatide exerts direct protective effects on endothelial cells through the AMPK/Akt/eNOS pathway in a GLP-1 receptor-dependent manner

2016 ◽  
Vol 310 (11) ◽  
pp. E947-E957 ◽  
Author(s):  
Rui Wei ◽  
Shifeng Ma ◽  
Chen Wang ◽  
Jing Ke ◽  
Jin Yang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Endothelial Cells ◽  
Endothelial Function ◽  
No Production ◽  
Dependent Manner ◽  
Protective Effects ◽  
Newly Diagnosed ◽  
Coronary Endothelial Function ◽  
Enos Phosphorylation

Glucagon-like peptide-1 (GLP-1) may have direct favorable effects on cardiovascular system. The aim of this study was to investigate the effects of the GLP-1 analog exenatide on improving coronary endothelial function in patients with type 2 diabetes and to investigate the underlying mechanisms. The newly diagnosed type 2 diabetic subjects were enrolled and given either lifestyle intervention or lifestyle intervention plus exenatide treatment. After 12-wk treatment, coronary flow velocity reserve (CFVR), an important indicator of coronary endothelial function, was improved significantly, and serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were remarkably decreased in the exenatide treatment group compared with the baseline and the control group. Notably, CFVR was correlated inversely with hemoglobin A1c (Hb A1c) and positively with high-density lipoprotein cholesterol (HDL-C). In human umbilical vein endothelial cells, exendin-4 (a form of exenatide) significantly increased NO production, endothelial NO synthase (eNOS) phosphorylation, and GTP cyclohydrolase 1 (GTPCH1) level in a dose-dependent manner. The GLP-1 receptor (GLP-1R) antagonist exendin (9–39) or GLP-1R siRNA, adenylyl cyclase inhibitor SQ-22536, AMPK inhibitor compound C, and PI3K inhibitor LY-294002 abolished the effects of exendin-4. Furthermore, exendin-4 reversed homocysteine-induced endothelial dysfunction by decreasing sICAM-1 and reactive oxygen species (ROS) levels and upregulating NO production and eNOS phosphorylation. Likewise, exendin (9–39) diminished the protective effects of exendin-4 on the homocysteine-induced endothelial dysfunction. In conclusion, exenatide significantly improves coronary endothelial function in patients with newly diagnosed type 2 diabetes. The effect may be mediated through activation of AMPK/PI3K-Akt/eNOS pathway via a GLP-1R/cAMP-dependent mechanism.

scholarly journals β-Cyclodextrin Inhibits Monocytic Adhesion to Endothelial Cells through Nitric Oxide-Mediated Depletion of Cell Adhesion Molecules

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3575
Author(s):  
Sujeong Jang ◽  
Seongsoo Lee ◽  
Heonyong Park
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Cell Adhesion ◽  
No Production ◽  
Aortic Endothelial Cells ◽  
Enos Phosphorylation ◽  
Inflammatory Processes ◽  
Cell Adhesion Molecule 1 ◽  
Endothelial Nitric Oxide ◽  
Inflammatory Effect

Cyclodextrins (CDs) are used as drug delivery agents. In this study, we examined whether CDs have an inflammatory effect on endothelial cells. First, we found that β-CD promoted cell proliferation in bovine aortic endothelial cells and elevated nitric oxide (NO) production through dephosphorylation of threonine-495 (T-495) in endothelial nitric oxide synthetase (eNOS). Dephosphorylation of T-495 is known to activate eNOS. Phosphorylation of T-495 was found to be catalyzed by protein kinase Cε (PKCε). We then found that β-CD inhibits binding of PKCε to diacylglycerol (DAG) via formation of a β-CD-DAG complex, indicating that β-CD inactivates PKCε. Furthermore, β-CD controls activation of PKCε by reducing the recruitment of PKCε into the plasma membrane. Finally, β-CD inhibits expression of intercellular and vascular cell adhesion molecule-1 by increasing NO via control of PKCε/eNOS and suppression of THP-1 cell adhesion to endothelial cells. These findings imply that β-CD plays an important role in anti-inflammatory processes.

Myocardial infarction triggers Inflammatory deterioration of vascular niche by accelerating loss of a specific vessel subtype in bone

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Hoffmann ◽  
G Luxan ◽  
W.T Abplanalp ◽  
T Rasper ◽  
A.M Fischer ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Endothelial Cells ◽  
Heart Disease ◽  
Chronic Heart Failure ◽  
Ischemic Heart Disease ◽  
Ischemic Heart ◽  
Vessel Length ◽  
Vascular Niche ◽  
The Impact

Abstract Introduction The interface between heart and bone emerges as a key trigger of post-infarction inflammation and progression of chronic heart failure (CHF). However, our knowledge on the underlying mechanisms of this interaction is incomplete. Bone vasculature, specifically so-called H-type (Endomucinhigh) endothelial cells (EC), plays a crucial role in maintenance of the bone integrity and regulation of hematopoietic stem cells (HSC). While previous studies in mice showed the reduction of H-type vessels by aging, the impact of ischemic heart disease is unclear. Therefore, we aimed to investigate the effects of myocardial infarction (MI) and chronic heart failure on the vascular bone cell composition in mice and humans. Methods and results Flow cytometric analysis of harvested bones at the different timepoints after MI induction in mice revealed a gradual loss of H-type endothelial cells in the time-course of developing chronic heart failure (P<0.05 at day 7 and 14 vs. control; P<0.0001 at day 28 vs. control). This results were confirmed in immunostainings of tibia sections showing a significant decrease of H-type vessel length after MI (p<0.05 at day 14 and 28, accordingly). The loss of type-H endothelium was accompanied by a significant expansion of long-term HSC in the bone (P=0.0005 at day 28 post MI vs. control). Importantly, type H ECs were also significantly reduced in the bone of ischemic post-infarct HF patients (n=16) compared with control subjects (n=8; P=0.0003). To gain insights into the mechanisms underlying the changes in the vascular niche, we performed single cells RNA sequencing of human BM ECs. These studies confirmed the decrease in Emcnexpressing ECs in ischemic HF patients, which was accompanied by significantly increased expression of inflammatory genes, including IL1b (P<0.0001). Inflammatory EC phenotypes and IL1b expression in HF could be further confirmed at protein level using cytospin immunostainings. Murine studies further revealed an early induction IL-1b specifically in H-type vessels already at day 1 after MI induction, which preceded the loss of H-type endothelium within the following 4 weeks. By inhibiting IL-1b production using a specific Nlrp3 inflammasome inhibitor (MCC950) we could observe a partial restoration of H-type EC frequencies (P=0.033) and a significant increase in H-type vessel length (p=0.035) at day 28 day after MI. Conclusions Our data show for the first time an impact of myocardial infarction and chronic heart failure on the bone marrow vasculature. These changes seem to be strongly associated with inflammatory response in H-type vessels, which precedes its loss after MI. Specifically, the induction of the inflammatory cytokine IL1b may contribute to the disturbed phenotype. This suggest that inhibition of IL1b (e.g. by canakinumab) be used as a novel strategy to prevent or reverse the deterioration of the vascular bone function in ischemic heart disease. Funding Acknowledgement Type of funding source: None

scholarly journals Effect of Hot Water Extracts of Maqui Berry on Human Aortic Endothelial Cells Exposed to a Hyperglycemic Environment

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 435-435
Author(s):  
Keith Martin
Keyword(s):  
Endothelial Cells ◽  
Endothelial Function ◽  
Final Concentration ◽  
Water Soluble ◽  
Hot Water ◽  
No Production ◽  
Aortic Endothelial Cells ◽  
Maqui Berry ◽  
Human Aortic Endothelial Cells ◽  
Aortic Endothelial

Abstract Objectives Impaired endothelial function is associated with many chronic vascular-related diseases including cardiovascular disease, inflammation, and diabetes. The antioxidant-rich Maqui berry (Aristotelia chilensis) has received increasing attention due to a variety of bioactivities including reduction of inflammation, control of blood glucose, and improvement of heart health, e.g., aortic endothelium, but corroborative research is needed. In the present study, we investigated the effects of aqueous Maqui berry extract (MBE) on nitric oxide (NO) production and oxidative stress (ROS) generation in human aortic endothelial cells (HAEC) alone or in a hyperglycemic environment with or without insulin. Methods Sterile (0.22 um filtered) MBE was added to endothelial basal medium (5% v/v) alone or containing glucose (final concentration 600 mg/dL; 33.3 mM) and/or insulin (final concentration 100 nM) followed by addition to monolayers and incubation for 24 hours. Monolayers were then assayed for NO production via the Greiss reaction, ROS via the use of DCFH-DA, and viability using MTT. Results We show that MBE may have increased ROS levels by 1.8-fold (P < 0.05) compared to control cultures using the DCFH-DA assay but decreased by ∼13% in the presence of glucose with or without insulin. MBE also increased NO levels by 3-fold (P < 0.05) compared to levels in control cultures. Glucose inclusion reduced NO by 15% and insulin reduced levels to that of control with or without glucose present. Viability, determined by MTT reduction, was not different between any of the groups. Conclusions The results suggest that water-soluble components of MB may modulate NO production in a hyperglycemic and/or hyperinsulinemic microenvironment and potentially improve endothelial function, in part, via the potential vasorelaxation properties of NO. Funding Sources School of Health Studies, University of Memphis.

scholarly journals Effects of Endothelin A Receptor Blockade on Endothelial Function in Patients With Chronic Heart Failure

Circulation ◽  
2001 ◽  
Vol 103 (7) ◽  
pp. 981-986 ◽  
Author(s):  
Rudolf Berger ◽  
Brigitte Stanek ◽  
Martin Hülsmann ◽  
Bernhard Frey ◽  
Sandra Heher ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Endothelial Function ◽  
Receptor Blockade ◽  
Endothelin A Receptor ◽  
Endothelin A
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