Association of endothelial nitric oxide synthase (eNOS) gene G894T polymorphism with hypertension risk and complications

ALrefai, Abeer Ahmed; Habib, Mona Salah El‐din; Yaseen, Rehab; Gabr, Mahmoud K; Habeeb, Rabab M

doi:10.1007/s11010-016-2790-2

Cited by 16 publications

(7 citation statements)

References 36 publications

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“…However, this effect was not observed in the arteries from Wistar rats in the present study, a result in line with that of Zhang et al ( 2004 ), implying that the effect of Rhy is to restore the impaired eNOS activity but not to increase the activity of normally functioning eNOS. As abnormal eNOS occurs commonly among patients with hypertension (Cengiz et al, 2015 ; ALrefai et al, 2016 ), these findings highlight that the patients with endothelial dysfunction might benefit from the endothelium-protective potential of Rhy.…”

Section: Discussionmentioning

confidence: 79%

Rhynchophylline Ameliorates Endothelial Dysfunction via Src-PI3K/Akt-eNOS Cascade in the Cultured Intrarenal Arteries of Spontaneous Hypertensive Rats

et al. 2017

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Objectives: To examine the protective effect of Rhynchophylline (Rhy) on vascular endothelial function in spontaneous hypertensive rats (SHRs) and the underlying mechanism.Methods: Intrarenal arteries of SHRs and Wistar rats were suspended in myograph for force measurement. Expression and phosphorylation of endothelial nitric oxide (NO) synthase (eNOS), Akt, and Src kinase (Src) were examined by Western blotting. NO production was assayed by ELISA.Results: Rhy time- and concentration-dependently improved endothelium-dependent relaxation in the renal arteries from SHRs, but had no effect on endothelium-independent relaxation in SHR renal arteries. Wortmannin (an inhibitor of phosphatidylinositol 3-kinase) or PP2 (an inhibitor of Src) inhibited the improvement of relaxation in response to acetylcholine by 12 h-incubation with 300 μM Rhy. Western blot analysis revealed that Rhy elevated phosphorylations of eNOS, Akt, and Src in SHR renal arteries. Moreover, wortmannin reversed the increased phosphorylations of Akt and eNOS induced by Rhy, but did not affect the phosphorylation of Src. Furthermore, the enhanced phosphorylations of eNOS, Akt, and Src were blunted by PP2. Importantly, Rhy increased NO production and this effect was blocked by inhibition of Src or PI3K/Akt.Conclusion: The present study provides evidences for the first time that Rhy ameliorates endothelial dysfunction in SHRs through the activation of Src-PI3K/Akt-eNOS signaling pathway.

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Section: Discussionmentioning

confidence: 79%

Rhynchophylline Ameliorates Endothelial Dysfunction via Src-PI3K/Akt-eNOS Cascade in the Cultured Intrarenal Arteries of Spontaneous Hypertensive Rats

et al. 2017

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“…Also, several studies showed a strong association between 894 G > T polymorphism of NOS3 gene and hypertension [18,38,39].…”

Section: Discussionmentioning

confidence: 99%

Prevalence of IGFBP3, NOS3 and TCF7L2 Polymorphisms and Their Association With Hypertension: A Population-Based Study With Brazilian Women of African Descent

Neto

Vasconcelos

Santos³

et al. 2020

Preprint

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Background: African ancestry seems to be a risk factor for hypertension; however, few genetic studies have addressed this issue. This study aimed to investigate the prevalence of polymorphisms NOS3; rs1799983, IGFBP3; rs11977526 and TCF7L2; rs7903146 in Brazilian women of African descent and their association with hypertension.Methods: This is a cross-sectional study with a sample of 1021 women (19–59 years old) from the quilombola communities of Alagoas (Brazil). Demographic, socioeconomic, lifestyle, anthropometric, biochemical, and blood pressure data were collected. DNA was extracted from mucosa epithelial cells of the participants’ cheek. Genotyping was performed by PCR allelic discrimination. Prevalence ratio (PR) was the measure of association, calculated by Poisson regression, with a hierarchical selection of variables.Results: The prevalences of the less frequent genotypes were 26.5% TT genotype of NOS3; rs1799983, 16.7% AA genotype of IGFBP3; rs11977526, and 18.3% TT genotype of TCF7L2; rs7903146. For these conditions, the prevalence of hypertension and PR (adjusted) relatively to the ancestral genotype were, respectively: 52.0% vs 24.5% (PR=1.54; p<0.001), 62.0% vs 24.1% (PR=1.59; p<0.001), and 38.9% vs 27.9% (PR=0.86; p=0.166). Associations with hypertension were statistically significant, except for the TCF7L2; rs7903146 polymorphism, after adjusted analysis. Conclusions: Brazilian Afro-descendant women with the TT genotype for the NOS3 gene and the AA genotype for the IGFBP3 gene are more susceptible to hypertension. The understanding of underlying mechanisms involving the pathogenesis of hypertension can motivate research for the development of new therapeutic targets related to nitric oxide metabolism and the management of oxidative stress.

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“…ТТ-генотип полиморфизма гена NOS3 был связан с риском атеросклеро- [35]. TT и GT генотипы были ассоциированы с риском ИБС [36,37] и АГ [38]. Результаты нашего исследования согласуются с исследованием Campedelli с соавт., где наличие GG-генотипа повышало предрасположенность к атеросклерозу [39].…”

Section: результаты и обсуждениеunclassified

Association of AGT, ACE, NOS3, TNF, MMP9, CYBA polymorphism with subclinical arterial wall changes

et al. 2021

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Aim Activation of the renin-angiotensin-aldosterone system, decreased nitric oxide production, chronic inflammation, and oxidative stress result in subclinical changes in the arterial wall, which favor the development of cardiovascular diseases (CVD). The effect of allelic gene variants that encode the proteins participating in pathogenetic pathways of age-associated diseases with subclinical changes in the arterial wall [increased pulse wave velocity (PWV), increased intima-media thickness, endothelial dysfunction (ED), presence of atherosclerotic plaques (ASP)] are understudied. This study analyzed the relationship between AGT, ACE, NOS3 TNF, MMP9, and CYBA gene polymorphism and the presence of subclinical changes in the arterial wall, including the dependence on risk factors for CVD, in arbitrarily healthy people of various age.Material and methods The relationship of polymorphisms с.521С>Т of AGT gene, Ins>Del of AСE gene, с.894G>T of NOS3 gene, – 238G>A of TNF gene, – 1562С>T of MMP9 gene, and c.214Т>С of CYBA gene with indexes of changes in the arterial wall and risk factors for CVD was studied in 160 arbitrarily healthy people by building models of multiple logistic regression and also by analyzing frequencies of co-emergence of two signs with the Pearson chi-squared test (χ2) and Fisher exact test.Results The DD-genotype of Ins>Del ACE gene polymorphism was correlated with increased PWV (p=0.006; odds ratio (OR) =3.41, 95 % confidence interval (CI): 1.48–8.67) and ED (p=0.014; OR=2.60, 95 % CI: 1.22–5.68). The GG genotype of с.894G>T NOS3 gene polymorphism was correlated with ED (p=0.0087; OR=2.65, 95 % CI: 1.26–5.72); the ТТ-genotype of с.894G>T NOS3 gene polymorphism was correlated with ASP (p=0.033; OR=0.034, 95 % CI: 0.001–0.549).Conclusion Polymorphic variants of AСE and NOS3 genes correlated with ED, increased arterial wall stiffness, and the presence of subclinical changes in the arterial wall.

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Association of endothelial nitric oxide synthase (eNOS) gene G894T polymorphism with hypertension risk and complications

Cited by 16 publications

References 36 publications

Rhynchophylline Ameliorates Endothelial Dysfunction via Src-PI3K/Akt-eNOS Cascade in the Cultured Intrarenal Arteries of Spontaneous Hypertensive Rats

Rhynchophylline Ameliorates Endothelial Dysfunction via Src-PI3K/Akt-eNOS Cascade in the Cultured Intrarenal Arteries of Spontaneous Hypertensive Rats

Prevalence of IGFBP3, NOS3 and TCF7L2 Polymorphisms and Their Association With Hypertension: A Population-Based Study With Brazilian Women of African Descent

Association of AGT, ACE, NOS3, TNF, MMP9, CYBA polymorphism with subclinical arterial wall changes

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