Impaired endothelial progenitor cell function predicts age-dependent carotid intimal thickening |
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Authors: | Stefanie Keymel MD Christoph Kalka MD Tienush Rassaf MD Yerem Yeghiazarians MD FACC Malte Kelm MD FESC Christian Heiss MD |
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Affiliation: | Medical Clinic I, Dept. of Medicine, Division of Cardiology, Pulmonology, and Vascular Medicine, RWTH University Hospital Aachen, Pauwelstrasse 30, 52074, Aachen, Germany. |
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Abstract: | Objectives We investigated whether qualitative or quantitative alterations of the endothelial progenitor cell (EPC) pool predict age-related structural vessel wall changes. Background We have previously shown that age-related endothelial dysfunction is accompanied by qualitative rather than quantitative changes of EPCs. Animal studies suggest that impaired EPC functions lead to accelerated arterial intimal thickening. Methods Intima-media thickness (IMT) was measured in the common carotid artery in our previously published groups of younger (25 ± 1 years, n = 20) and older (61 ± 2 years, n = 20) healthy non-smoking volunteers without arterial hypertension, hypercholesterolemia, and diabetes mellitus. Endothelial progenitor cells (EPCs, KDR+/CD34+ and KDR+/CD133+) were counted in peripheral blood using flow cytometry. In ex vivo expanded EPCs, the function was determined as chemotaxis to VEGF, proliferation, and survival. Results We observed thicker IMT in older as compared to younger subjects (0.68 ± 0.03 mm Vs. 0.48 ± 0.02 mm, P < 0.001). Importantly, there were significant inverse univariate correlations between IMT, EPC chemotaxis, and survival (r = −0.466 P < 0.05; r = −0.463, P < 0.01). No correlation was observed with numbers of circulating EPCs. Multivariate regression analysis revealed that age, mean arterial pressure and migration of EPCs were independent predictors of IMT (R 2 = 0.58). Conclusion Impaired EPC function may lead to accelerated vascular remodeling due to chronic impairment of endothelial maintenance. Returned for 1. Revision: 13 December 2007 1. Revision received: 16 June 2008 Returned for 2. Revision: 20 June 2008 2. Revision received: 17 July 2008 |
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Keywords: | aging Intima-media thickness endothelial progenitor cells |
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