Since patients with the metabolic syndrome are known to have endothelial dysfunction, we aimed to investigate if the significance of NOS3 polymorphisms may depend on the presence of the metabolic syndrome.
LacCer causes endothelial dysfunction with potential mechanisms of the down-regulation of eNOS and increase of oxidative stress due to the activation of NADPH oxidase and inhibition of internal antioxidant catalase.
In rhAPC-treated aorta and mesenteric arteries, contractility and endothelial responsiveness to vasodilator drug and shear stress were improved. rhAPC treatment also improved LPS-induced endothelial dysfunction; this effect was associated with an increase in the phosphorylated form of endothelial nitric oxide synthase and protein kinase B as well as cyclooxygenase vasodilatory pathways, thus suggesting that these pathways, together with the decrease in nuclear factor-kappaB activation and inducible nitric oxide synthase expression in the vascular wall, are implicated in the endothelial effect of rhAPC.
Polymorphisms in the endothelial nitric oxide synthase ( eNOS ) gene (- 786T > C and 894G > T ) enhance endothelial dysfunction and have been studied in relation to coronary artery disease (CAD).
In contrast, IVA maintained and PT improved cerebral endothelial nitric oxide synthase-dependent flow-mediated dilation and wall compliance, and both interventions reduced MMP-9 activity (P < 0.05); METO worsened endothelial dysfunction and compliance and did not reduce MMP-9 activity.
In conclusion, the age-dependent cerebral endothelial dysfunction is precocious in dyslipidemia and involves TXA₂ production that limits eNOS activity.
Previous studies suggest that the higher risk observed in T allele carriers is due to endothelial dysfunction associated with a lower eNOS activity and that acute consumption of phenol-rich olive oil ameliorates postprandial endothelial dysfunction by reducing oxidative stress and increasing nitric oxide bioavailability.
DFS significantly improved endothelial dysfunction (89.9 ± 3.9% vs. 79.2 ± 4.3% relaxation at 10(-4) mol/l acetylcholine, p < 0.05) associated with increased endothelial nitric oxide synthase phosphorylation and reduced atherosclerotic lesion area (17.7% [15.6% to 25.8%] vs. 24.6% [19.3% to 34.6%], p < 0.01) compared with vehicle treatment.
As the number of therapeutic molecules that modulate the expression and activity of eNOS increases, further detailed research is required to reveal their mode of action in preventing and/or reversing the endothelial dysfunction.
Epigenetic processes are likely to underlie such effects, but there is to date no evidence that endothelial dysfunction in early life results from epigenetic processes on key genes in the NO system, such as NOS3 (eNOS) and ARG2 (arginase-2).
The polymorphic variants of endothelial nitric oxide synthase (eNOS) gene have been implicated in endothelial dysfunction and are highly relevant to macroangiopathies.
We tested the hypothesis that women with gestational diabetes mellitus (GDM) and their fetuses would demonstrate alterations in markers of endothelial nitric oxide synthase (eNOS) uncoupling, oxidative stress, and endothelial dysfunction and these changes would correlate with the levels of hyperglycemia through a pilot observational case-control study of women with GDM and their fetuses.
Because candidate genes responsible for susceptibility to ankylosing spondylitis are mostly unknown and available data suggest that there may be problems related to the nitric oxide pathway, such as endothelial dysfunction and increased asymmetric dimethylarginine, this study aimed to assess the association of common endothelial nitric oxide synthase gene polymorphisms with ankylosing spondylitis.
Genetic variants in endothelial nitric oxide synthase gene (NOS3) leading to endothelial dysfunction may be predispose to the coronary slow-flow phenomenon (CSFP).
Fluid shear stress has been revealed to differentially regulate endothelial nitric oxide synthase (eNOS) distribution in vessels. eNOS, a key enzyme in controlling nitric oxide (NO) release, has a crucial role in mediating oxidative stress, and resveratrol (RSV)‑mediated eNOS also attenuates oxidative damage and suppresses endothelial dysfunction.
Glyoxalase I reduces glycative and oxidative stress and prevents age-related endothelial dysfunction through modulation of endothelial nitric oxide synthase phosphorylation.
Although no association of IGF-1 and IGFBP-3 levels with angiopoietin-2 or osteopontin was found, an inverse correlation between IGF-1 levels and asymmetric dimethylarginine (ADMA), an endogenous endothelial nitric oxide synthase inhibitor that impairs nitric oxide production and secretion promoting endothelial dysfunction, was found (r=-0.397; P=0.04).
In accordance, WT obese mice revealed decreased endothelium-dependent relaxations to acetylcholine despite of higher eNOS protein level, whereas Arg-II(-/-) obese mice were protected from HFD-induced eNOS-uncoupling and endothelial dysfunction, which was associated with reduced p38mapk activation in aortas of the Arg-II(-/-) obese mice.
We suggest that eNOS intron 4 gene polymorphism is related to endothelial dysfunction and subclinical atherosclerosis and could be a possible genetic marker for prediction of increased susceptibility to cardiovascular complications.