Association between atherogenic risk-modulating proteins and endothelium-dependent flow-mediated dilation in coronary artery disease patients

Andrea Tryfonos, Joseph Mills, Daniel J. Green, Anton J. M. Wagenmakers, Ellen A. Dawson, Matthew Cocks

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Purpose Endothelial dysfunction is an early and integral event in the development of atherosclerosis and coronary artery disease (CAD). Reduced NO bioavailability, oxidative stress, vasoconstriction, inflammation and senescence are all implicated in endothelial dysfunction. However, there are limited data examining associations between these pathways and direct in vivo bioassay measures of endothelial function in CAD patients. This study aimed to examine the relationships between in vivo measures of vascular function and the expression of atherogenic risk-modulating proteins in endothelial cells (ECs) isolated from the radial artery of CAD patients. Methods Fifty-six patients with established CAD underwent trans-radial catheterization. Prior to catheterization, radial artery vascular function was assessed using a) flow-mediated dilation (FMD), and b) exercise-induced dilation in response to handgrip (HE%). Freshly isolated ECs were obtained from the radial artery during catheterization and protein content of eNOS, NAD(P)H oxidase subunit NOX2, NF kappa B, ET-1 and the senescence markers p53, p21 and p16 were evaluated alongside nitrotyrosine abundance and eNOS Ser(1177) phosphorylation. Results FMD was positively associated with eNOS Ser(1177) phosphorylation (r = 0.290, P = 0.037), and protein content of p21 (r = 0.307, P = 0.027) and p16 (r = 0.426, P = 0.002). No associations were found between FMD and markers of oxidative stress, vasoconstriction or inflammation. In contrast to FMD, HE% was not associated with any of the EC proteins. Conclusion These data revealed a difference in the regulation of endothelium-dependent vasodilation measured in vivo between patients with CAD compared to previously reported data in subjects without a clinical diagnosis, suggesting that eNOS Ser(1177) phosphorylation may be the key to maintain vasodilation in CAD patients.

Original languageEnglish
Pages (from-to)367-380
Number of pages14
JournalEuropean Journal of Applied Physiology
Volume123
Issue number2
Early online date28 Oct 2022
DOIs
Publication statusPublished - Feb 2023

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