Interaction Between Endothelial Nitric Oxide Synthase Gene Polymorphisms (−786T&gt;C, 894G&gt;T and Intron 4 a/b) and Cardiovascular Risk Factors in Acute Coronary Syndromes

Piccoli, Jacqueline da Costa Escobar; Manfredini, Vanusa; Hamester, Fernanda Irma Remus; Bandinelli, Josiane Bettim; Turkienicz, Ilan Maltz; Chies, José Artur Bogo; Peres, Alessandra; Bodanese, Luiz Carlos; Bogo, Maurı́cio Reis

doi:10.1016/j.arcmed.2012.03.011

Cited by 25 publications

(19 citation statements)

References 34 publications

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“…This result is similar to that of Piccoli et al (2012), where they analyzed a South-Brazilian population and found a greater prevalence of the TC genotype in patients with acute coronary syndrome (ACS) and controls. Ragia et al (2010) found that the TC genotype (55.2% in the case group and 54.8% in control) had a higher prevalence concerning the other genotypes and they also did not find a statistically significant difference for patients who underwent myocardial revascularization surgery.…”

Section: Discussionsupporting

confidence: 73%

Research Article Atherosclerosis: analysis of the eNOS (T786C) gene polymorphism.

Barbosa¹,

Silva²,

Lagares³

et al. 2017

Genet. Mol. Res.

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ABSTRACT. The coronary arteriosclerotic disease is the most common cardiovascular disease. Atherosclerosis affects large-and medium-sized arteries leading to severe thrombosis or artery stenosis that could evolve to myocardial infarction, ischemic stroke, ischemic injury of kidneys and intestines, and several other life-threatening clinical manifestations. Nitric oxide has been shown to be a promising therapeutic agent against cardiovascular diseases. The eNOS gene assumes several important functions, including regulation of vascular tone and regional blood flow, the suppression of vascular smooth muscle cell proliferation, and modulation of leukocyte-endothelium interactions. The T786C polymorphism is an important point mutation, where thymine is changed to cytosine. T786C significantly reduces the activity of the eNOS promoter gene. Two hundred and ninety-seven peripheral blood samples were collected from patients with the previous diagnosis of atherosclerotic disease based on clinical examination and confirmed by imaging methods. Results were compared using the chisquare test and the G-test. In the present study, the TC genotype was more frequent in both case and control groups with no statistically significant difference. Comparing the relation TC/TT and CC genotypes in the case and control groups, there was no statistically significant difference. No significant difference was found when genotypes were analyzed regarding gender and smoking. Our results suggest a strong tendency of the T allele, in single or double dose, to be associated with atherosclerosis that was not confirmed by the scientific data.

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Section: Discussionsupporting

confidence: 73%

Research Article Atherosclerosis: analysis of the eNOS (T786C) gene polymorphism.

Barbosa¹,

Silva²,

Lagares³

et al. 2017

Genet. Mol. Res.

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“…36 Furthermore, this polymorphism has been associated with low plasma NO concentrations and with higher risk of CAD development. 35,37 In our study, the longitudinal variations of sCD40L were correlated with this polymorphism, suggesting a relationship of G894T polymorphism with endothelial dysfunction along disease progression.…”

Section: Discussionmentioning

confidence: 70%

“…35 The T786C polymorphism results in the replacement of thymine by cytosine. 35 In our study, the eNOS G894T polymorphism was associated with the longitudinal variations of sCD40L in AMI (F 5 6.9; P 5 0.01) but not in SA patients (F 5 0.001; P 5 0.97) and in CTR subjects (r 5 20.35; P 5 0.79). No significant associations were observed between sCD40L and the eNOS T786C polymorphism in AMI (F 5 0.21; P 5 0.65), SA (F 5 0.14; P 5 0.72), or CTR groups (r 5 20.11; P 5 0.96).…”

Section: Cd40lmentioning

confidence: 99%

Changes of soluble CD40 ligand in the progression of acute myocardial infarction associate to endothelial nitric oxide synthase polymorphisms and vascular endothelial growth factor but not to platelet CD62P expression

Napoleão

Monteiro

Cabral

et al. 2015

Translational Research

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Abbreviations: AMI ¼ acute myocardial infarction; APC ¼ allophycocyanin; Asp ¼ aspartate; cTNT ¼ cardiac troponin; CAD ¼ coronary artery disease; CRP ¼ C-reactive protein; CK ¼ creatine kinase; eNOS ¼ endothelial nitric oxide synthase; ELISA ¼ enzyme-linked immunosorbent assay; FITC ¼ fluorescein isothiocyanate; FAU ¼ fluorescence arbitrary units; Glu ¼ glutamic acid; LME ¼ linear mixed effects model; MPs ¼ microparticles; NO ¼ nitric oxide; NT-proBNP ¼ N-terminal pro-brain natriuretic peptide; PCI ¼ percutaneous coronary intervention; PBS ¼ phosphate-buffered saline; PE ¼ Phycoerythrin; CD62P ¼ P-selectin; sCD40L ¼ soluble CD40 ligand; SA ¼ stable angina pectoris; VEGF ¼ vascular endothelial growth factor INTRODUCTION CD40L is a signaling molecule, 1-3 implicated in thrombosis and inflammatory response to vascular injury. [4][5][6] The relationship of CD40L with coronary artery disease (CAD) has been established, 2,7-9 as also its implication in endothelial dysfunction. [10][11][12][13][14] However, whether the soluble CD40 ligand (sCD40L) could also influence endothelial dysfunction after acute myocardial infarction (AMI) injury remains unclear.In vitro studies have shown that sCD40L inhibits angiogenesis and also growth factor-induced human umbilical vein endothelial cell migration, which is achieved by generation of free radicals and inhibition of nitric oxide (NO) production. 10 The authors hypothesized that the sCD40L could inhibit reendothelialization of an injured vessel, thereby affecting the restenosis. 10Research efforts have been directed toward the finding of biomarkers to assess endothelial function and its correlation with AMI. Genetic indicators, such as the polymorphisms of endothelial NO synthase (eNOS) gene, 15,16 may provide insight into endothelial cells function.Vascular endothelial growth factor (VEGF) is a wellknown promoter of angiogenesis and an endogenous regulator of endothelial integrity. [17][18][19] The prognostic information provided by VEGF independently of other markers likely points toward an important role for angiogenesis in regulating myocardial repair and reperfusion after AMI. 17,20 Current opinion suggests a differential role of CD40L (both soluble and membrane-bound forms, which includes microparticles in circulation) 21 at different stages of CAD, contrasting with the traditional view of an unvarying function of the CD40L-CD40-sCD40L system interactions in the disease. 6 In that perspective, no clear indication of the interplay of CD40L with endothelial and vascular function markers and their importance in the pathophysiology of the AMI has been obtained so far in human clinical studies. Therefore, the aim of this study was to evaluate the relationship of sCD40L with markers of platelet activation, endothelial and vascular function during an early recovery period after AMI. To achieve this goal, the time changes over 1 month of sCD40L levels were assessed in AMI patients and correlated with the CD40L expressed on platelets and microparticles, CD62P expression on platele...

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“…Prevalence of G894T eNOS polymorphism has been associated with physiological alterations and worse clinical outcomes, for example, low plasma NO concentrations and risk of CAD development. 16,38 This polymorphism leads to a conservative replacement of glutamate with aspartate causing conformational alterations. 39 Consequently, eNOS susceptibility to proteolytic cleavage in endothelial cells and vascular tissues is higher, which has a functional effect on the enzyme, 39 and subsequently on NO bioactivity.…”

Section: Discussionmentioning

confidence: 99%

“…16 T786C polymorphism result in a replacement of thymine by cytosine at nucleotide-786 position, decreasing transcription of eNOS gene and reducing in half the promoter activity. 15 MicroRNA quantification analysis.…”

Section: Translational Significancementioning

confidence: 99%

Stratification of ST-elevation myocardial infarction patients based on soluble CD40L longitudinal changes

Napoleão

Cabral

Selas

et al. 2016

Translational Research

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Involvement of soluble CD40 ligand (sCD40L) in thrombosis and inflammation on the context of coronary artery disease is currently being revised. In that perspective, we had studied the association of sCD40L with markers of platelet activation and markers of endothelial and vascular function. On that cohort, a stratification of patients with acute myocardial infarction (AMI) 1 month after percutaneous coronary intervention (PCI) was observed based on concentrations of sCD40L. The study intended to identify the groups of AMI patients with different profiles of sCD40L concentrations and verify how medication, clinical evolution, biochemical data, and markers of regulation of endothelial function at genetic (endothelial nitric oxide synthase polymorphisms) and post-transcriptional levels (circulating microRNAs) affect sCD40L serum levels. Lower quartiles of sCD40L (,2.3 ng/mL) were associated with higher concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP), high frequency of G894T polymorphism, and altered expression of a set of microRNAs assumed to be involved in the regulation of endothelial and cardiac function and myocardium hypertrophy, relative to patients in sCD40L upper quartiles. A characteristic sCD40L variation pattern in STEMI patients was identified. Low levels of sCD40L 1 month after PCI distinguish STEMI patients with worse prognosis, a compromised cardiac healing, and a persistent endothelial dysfunction, as given by the association between sCD40L, NT-proBNP, G894T polymorphism, and specific profile of miRNA expression. These results suggest sCD40L could have a prognostic value in STEMI patients. (Translational Research 2016;176:95-104) Abbreviations: AMI ¼ acute myocardial infraction; CAD ¼ coronary artery disease; eNOS ¼ endothelial nitric oxide synthase; miR ¼ microRNA; NT-proBNP ¼ N-terminal pro-brain natriuretic peptide; PCI ¼ percutaneous coronary intervention; sCD40L ¼ soluble CD40 ligand; STEMI ¼ ST segment elevation myocardial infraction

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Interaction Between Endothelial Nitric Oxide Synthase Gene Polymorphisms (−786T>C, 894G>T and Intron 4 a/b) and Cardiovascular Risk Factors in Acute Coronary Syndromes

Cited by 25 publications

References 34 publications

Research Article Atherosclerosis: analysis of the eNOS (T786C) gene polymorphism.

Research Article Atherosclerosis: analysis of the eNOS (T786C) gene polymorphism.

Changes of soluble CD40 ligand in the progression of acute myocardial infarction associate to endothelial nitric oxide synthase polymorphisms and vascular endothelial growth factor but not to platelet CD62P expression

Stratification of ST-elevation myocardial infarction patients based on soluble CD40L longitudinal changes

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