Levels of nitric oxide metabolites, adiponectin and endothelin are associated with SNPs of the adiponectin and endothelin genes
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01.10.2019 |
Gumanova N.
Klimushina M.
Smetnev S.
Kiseleva A.
Skirko O.
Meshkov A.
Shanoyan A.
Kots A.
Metelskaya V.
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Biomedical Reports |
10.3892/br.2019.1238 |
0 |
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© 2019, Spandidos Publications. All rights reserved. Adiponectin, endothelin and nitric oxide (NO) are major regulators of vascular function. An imbal-ance of vasoactive factors contributes to the onset and progression of atherosclerosis. Various single nucleotide polymorphisms (SNPs) are considered to be risk factors for coronary heart disease. However, the molecular mechanisms of their associations with the components of endothelial dysfunction are poorly understood. In the present study, rs17366743, rs17300539, rs266729, rs182052 and rs2241766 SNPs of the adiponectin (ADIPOQ) gene and rs2070699, rs1800542 and rs1800543 SNPs of the endothelin-1 (EDN1) gene were genotyped in 477 patients with coronary heart disease who were subjected to coronary angiography, in order to determine the presence or absence of coronary atherosclerosis. The serum levels of adiponectin, endothelin and stable metabolites of NO, (nitrate and nitrite NOx), were assayed and their associations with the SNP genotypes and coronary lesions were calculated. The results indicated that rs17366743 of the ADIPOQ gene and rs2070699 and rs1800543 of the EDN1 gene were associated with the levels of NOx in women, which in turn was associated with cardiovascular mortality. In men, rs182052 and rs266729 of the ADIPOQ gene were associated with adiponectin levels, whereas rs17366743 of the ADIPOQ gene was associated with endothelin levels. Additionally, these SNPs were indirectly associated with the prevalence of coronary lesions in men. Therefore, the tested SNPs can be considered potential risk factors that lead to imbalance of vasoactive mediators in a gender-specific manner and contribute to the development of clinical manifestations of atherosclerosis.
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Ultrasonic dopplerography for the evaluation of endothelial function in the conduct of pharmacological vascular samples in an experiment
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13.08.2018 |
Soldatov V.
Malorodova T.
Pokrovskaya T.
Pokrovskii M.
Kulchenkova T.
Ksenofontov A.
Filippova O.
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International Journal of Research in Pharmaceutical Sciences |
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1 |
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© 2018 Pharmascope Publications. All rights reserved. To study the function of the endothelium in conducting vascular pharmacological samples in normal and blocking the synthesis of nitric oxide by ultrasound examination of the velocity of central blood flow in the femoral artery in comparison with the changes in systemic hemodynamics and the linear velocity of microcirculatory flow using laser flowmetry. It was studied the parameters of the blood flow velocity (the maximum systolic and diastolic velocity, average systolic and diastolic velocity, Gosling index of pulsatility and resistance index by the Doppler ultrasound Minimax-Doppler-K), the parameters of central circulation ("Biopac-systems MP-150", AcqKnowledge 4.2, USA), and linear velocity of the microcirculatory flow of the musculus vastus medialis (Biopac MP-150, USA) in intact animals and rats with N-Ni-tro-L-arginine methyl ester (L-NAME) induced deficiency of nitric oxide. Quantitative evaluation of endothelial dysfunction in the conduct of pharmacological tests with endothelium-dependent (acetylcholine) and endothe-lium-independent (sodium nitroprusside) vasodilatation is most indicative in calculating the coefficient reflecting the ratio of vascular responses areas in intact rats with L-NAME induced deficiency of nitric oxide. Blood flow parameters (the maximum systolic velocity, the calculated difference between systolic and diastolic velocities) showed a high correlation, both with mean arterial pressure and a linear velocity of the microcirculatory flow. We conclude, that ultrasound Doppler were reflected in the systemic and local vascular response to the administration of vasodilators. It allows an assessment of endothelial function by using the Minimax-Doppler-K device.
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Prognostic significance of endothelial dysfunction markers in arterial hypertension
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01.01.2018 |
Podzolkov V.
Bragina A.
Druzhinina N.
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Russian Journal of Cardiology |
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0 |
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© 2018, Silicea-Poligraf. All rights reserved. Aim. Assessment of prognostic significance of endothelial dysfunction markers: stable metabolites of nitric oxide (NOx), von Willebrand factor (vWF), endothelin-1 (E1), homocysteine and tissue plasminogen activator (tPA) in essential hypertension (EAH) patients not taking antihypertension therapy systematically. Material and methods. Totally, 12 EAH patients investigated (45 males, 79 females) (mean age 51,4±6,5 y.o., mean duration of AH 7,9±7,3 y.). Concentration of NOx in plasma was measured by spectrophotometry, and of vWF, homocysteine, E1 and tPA — by immune enzyme assay. Results. By the increase of SCORE risk level, there was significant increase of concentrations of NOx, E1, homocysteine and vWF in EAH patients (p<0,05), there were no changes in tPA levels (p>0,05). In 8 (8±1,1) years after baseline assessment, 115 patients were assessed second time. Of those 13 (11,3%) had cardiovascular events (CVE) and 5 (4,3%) died. By single factorial regression, the rate of CVE in EAH patients relate to homocystein level (р=0,01), NOx (р=0,001) and vWF (р=0,001). By multifactorial analysis, prognostic statistical significance is found for NOx (relative risk (RR) =3,8, р=0,006) and vWF (RR =3,5, р=0,005). In ROC-analysis there were found threshold levels of NOx (>46,6 mcM/L, AUC =0,863) and vWF (>1,68 mg/dL, AUC =0,738), the increase of which is followed by CVE development risk for the levels of NOx >46,6 mcM/L 3,8 times (sensitivity 81,9% and specificity 65,8%), vWF >1,68 mg/dL — 3,5 times (sensitivity 74,3% and specificity 62,7%). Combination of the parameters point on the risk increase up to 6,5 times (р=0,00007). Conclusion. NOx with the threshold of >46,6 mcM/L (RR =3,8) and vWF >1,68 mg/dL (RR =3,5) do show independent prognostic value for 5-year CVE risk assessment in EAH patients that can be applied as an additional method for risk stratification to estimate a group for more aggressive therapy and CVE prevention.
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Relation of smoking and endothelial dysfunction markers in systemic hypertension
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01.01.2018 |
Podzolkov V.
Bragina A.
Druzhinina N.
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Cardiovascular Therapy and Prevention (Russian Federation) |
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0 |
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© 2018 Vserossiiskoe Obshchestvo Kardiologov. All rights reserved. Aim. Assessment of the markers levels of endothelial dysfunction (ED): stable metabolites of nitric oxide (NOx), endothelin-1 (E1), homocysteine (HC), von Willebrand factor (vWF) and tissue plasminogen activator (tPA) in blood plasma of smoker and nonsmoker patients with arterial hypertension (AH) of low and moderate risk, not taking antihypertension therapy regularly. Material and methods. Totally, 124 AH patients included, 45 males and 79 females, mean age 51,4±6,5 y. O., mean AH duration 7,9±7,3 y. Controls included 35 healthy volunteers (20 males, 15 females). Concentration of NOx in plasma was measured with spectrophotometry, and of vWF, HC, E1 and tPA-with immune enzyme assay. Results. To evaluate the relation of smoking and ED markers levels, AH patients and controls were selected to subgroups according to smoking status: smoker (35,5%) and non-smoker (64,5%) AH patients; smoker (38%) and non-smoker (62%) controls. In smoker AH patients comparing to non-smoking there were significantly higher concentrations of NOx-48,2±18,8 mcM/L and 40,3±21,2 mcM/L, respectively (p<0,05), E1-1,2±0,16 and 0,6±0,2 fM/L, resp. (p<0,05), HC-25,7±6,04 and 16,2±6,5 mcM/L, resp. (p<0,05), vWF-1,39±0,7 and 1,1±0,6 mg/dL, resp (p<0,05) and tPA-13,05±6,2 and 8,5±6,2 mcM/L, resp. (p<0,05). There was correlation in the AH group, of NOx concentration and smoking (r=0,46, p<0,05), and tobacco smoking duration (r=0,83, p<0,05). Also, there were positive correlations of HC and smoking (r=0,4, p<0,05). In control group smokers had higher HC-20,7±5,3 and 17,2±4,7 mcM/L, resp. (p<0,05), vWF-1,3±0,8 and 0,8±0,6 mg/dL, resp. (p<0,05) and tPA-11,1±6,5 and 6,6±5,2 mcM/L, resp. (p<0,05). There were no significant changes in NOx and E1. Conclusion. In smokers of both AH and control groups the levels of HC, vWF and tPA were significantly higher in comparison with nonsmokers. In smoker AH patients the mean concentrations of NOx and E1 are higher than in non-smoker patients. Levels of ED are related with not only the fact of smoking itself (p<0,05), but smoking duration (p<0,05).
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