Impaired vascular function and repair in patients with premature coronary artery disease

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
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Boulberdaa, Dr Mounia and Baker, Professor Andrew
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 > Institute of Cardiovascular and Medical Sciences
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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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
637071BHF Centre for regenerative medicineAndrew BakerBritish Heart Foundation (BHF)RM/13/2/30158RI CARDIOVASCULAR & MEDICAL SCIENCES