Brittan, M., Hunter, A., Boulberdaa, M., Fujisawa, T., Skinner, E. M., Shah, A. S., Baker, A.H. and Mills, N. L. (2015) Impaired vascular function and repair in patients with premature coronary artery disease. European Journal of Preventive Cardiology, 22(12), pp. 1557-1566. (doi: 10.1177/2047487315600169) (PMID:26276790)
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Abstract
Background Endothelial dysfunction is central to the pathogenesis of coronary artery disease, but the role of local and circulating endothelial progenitor cells in maintaining vascular health is poorly understood. We hypothesised that impaired local and circulating vascular repair mechanisms predispose to endothelial dysfunction and the premature onset of coronary artery disease. Methods and results Patients with premature coronary artery disease (n = 16) and healthy age- and sex-matched controls (n = 16) underwent venous occlusion plethysmography with intra-arterial infusion of acetylcholine and sodium nitroprusside. Numbers of circulating endothelial progenitor cells were directly quantified in whole blood by flow cytometry. Endothelial cells were isolated from the blood vessel wall and from peripheral blood mononuclear cells, and expanded in vitro for phenotypic and functional characterisation and analysis of microRNA expression levels. A dose-dependent increase in forearm blood flow (p < 0.001) was attenuated in response to the endothelial-dependent vasodilator acetylcholine in patients compared with controls (p = 0.03). No differences in the number of circulating endothelial progenitor cells or in the phenotype, function or microRNA expression levels of endothelial outgrowth cells isolated from blood were observed in patients and controls. Conversely, local vessel wall endothelial cells from patients had significant impairments in proliferation, adhesion and migration, and significantly reduced expression levels of microRNAs known to regulate endothelial function (miRs −10 a, −let7b, −126 and −181 b) (p < 0.05 for all). Conclusion Local vessel wall derived endothelial cells, rather than circulating endothelial progenitor cells and their progeny, are impaired in patients with vascular dysfunction and premature coronary artery disease.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Baker, Professor Andrew and Boulberdaa, Dr Mounia |
Authors: | Brittan, M., Hunter, A., Boulberdaa, M., Fujisawa, T., Skinner, E. M., Shah, A. S., Baker, A.H., and Mills, N. L. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
Journal Name: | European Journal of Preventive Cardiology |
Publisher: | SAGE Publications |
ISSN: | 2047-4873 |
ISSN (Online): | 2047-4881 |
Published Online: | 10 August 2015 |
Copyright Holders: | Copyright © 2016 The Authors |
First Published: | First published in European Journal of Preventive Cardiology 22(12:1557-1566 |
Publisher Policy: | Reproduced under a Creative Commons License |
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