Search results for "Vasoprotective"
showing 7 items of 7 documents
A non-canonical chemical feedback self-limits nitric oxide-cyclic GMP signaling in health and disease
2018
Endothelial nitric oxide (NO) stimulates the heme protein, soluble guanylyl cyclase (sGC) to form vasoprotective cyclic GMP (cGMP). In different disease states such as pulmonary hypertension, NO-cGMP signaling is pharmacologically augmented, yet the pathomechanisms leading to its dysregulation are incompletely understood. Here we show in pulmonary artery endothelial cells that endogenous NO or NO donor compounds acutely stimulate sGC activity, but chronically down-regulate both sGC protein and cGMP formation. Surprisingly, this endogenous feedback mechanism was independent of canonical cGMP signaling via cGMP-dependent protein kinase. It did not involve thiol-dependent modulation, a process…
Investigating the Vascular Toxicity Outcomes of the Irreversible Proteasome Inhibitor Carfilzomib
2020
Background: Carfilzomib&rsquo
Red wine increases the expression of human endothelial nitric oxide synthase
2003
Abstract Objectives The study tested the effect of red wine on endothelial-type nitric oxide synthase (eNOS) expression and eNOS activity in human endothelial cells. Background Endothelial-type nitric oxide (NO) synthase exerts vasoprotective effects. Moderate alcohol consumption has been associated with a reduction of cardiovascular disease, and red wine seems to offer more benefits than any other type of drink. However, the molecular basis of this protective effect is unclear. Methods Human endothelial cells were treated with red wine, and eNOS messenger ribonucleic acid (mRNA) expression was measured by RNase protection assay, eNOS protein expression by Western blotting, and eNOS activit…
Antiatherosclerotic Effects of Small-Molecular-Weight Compounds Enhancing Endothelial Nitric-Oxide Synthase (eNOS) Expression and Preventing eNOS Unc…
2008
Many cardiovascular diseases are associated with reduced levels of bioactive nitric oxide (NO) and an uncoupling of oxygen reduction from NO synthesis in endothelial NO synthase (eNOS uncoupling). In human endothelial EA.hy 926 cells, two small-molecular-weight compounds with related structures, 4-fluoro-N-indan-2-yl-benzamide (CAS no. 291756-32-6; empirical formula C16H14FNO; AVE9488) and 2,2-difluoro-benzo[1,3]dioxole-5-carboxylic acid indan-2-ylamide (CAS no. 450348-85-3; empirical formula C17H13F2NO3; AVE3085), enhanced eNOS promoter activity in a concentration-dependent manner; with the responsible cis-element localized within the proximal 263 base pairs of the promoter region. RNA int…
Uncoupling of eNOS in Cardiovascular Disease
2017
Abstract Under physiological conditions, nitric oxide (NO) produced by the endothelial NO synthase (eNOS) represents a key vasoprotective factor. Under conditions of cardiovascular diseases, such as hypertension, diabetes, and atherosclerosis, eNOS may become uncoupled. Uncoupled eNOS generates superoxide at the expense of NO and contributes significantly to endothelial dysfunction and atherogenesis. Major mechanisms of eNOS uncoupling include depletion of tetrahydrobiopterin, an essential cofactor for the eNOS enzyme, and deficiency of l -arginine, the eNOS substrate, and/or eNOS S-glutathionylation. Reversal of eNOS uncoupling may represent a novel therapeutic strategy for the prevention …
Midostaurin upregulates eNOS gene expression and preserves eNOS function in the microcirculation of the mouse
2005
Nitric oxide (NO) derived from endothelial NO synthase (eNOS) is a powerful vasodilator and possesses vasoprotective effects. Therefore, augmentation of eNOS expression and -activity by pharmacological means could provide protection against cardiovascular disease. However, this concept has been questioned recently, because in several disease models, eNOS upregulation was associated with a dysfunctional enzyme (referred to as eNOS uncoupling). In contrast, the present study demonstrates that an eNOS gene expression-enhancing compound with additional protein kinase C (PKC) inhibitory properties can upregulate eNOS while preserving its enzymatic function. Apolipoprotein E-knockout mice were tr…
Artichoke, Cynarin and Cyanidin Downregulate the Expression of Inducible Nitric Oxide Synthase in Human Coronary Smooth Muscle Cells
2014
Artichoke (Cynara scolymus L.) is one of the world’s oldest medicinal plants with multiple health benefits. We have previously shown that artichoke leaf extracts and artichoke flavonoids upregulate the gene expression of endothelial-type nitric oxide synthase (eNOS) in human endothelial cells. Whereas NO produced by the eNOS is a vasoprotective molecule, NO derived from the inducible iNOS plays a pro-inflammatory role in the vasculature. The present study was aimed to investigate the effects of artichoke on iNOS expression in human coronary artery smooth muscle cells (HCASMC). Incubation of HCASMC with a cytokine mixture led to an induction of iNOS mRNA expression. This iNOS induction was c…