Impaired endothelial progenitor cell function predicts age-dependent carotid intimal thickening.
OBJECTIVE
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).


CONCLUSIONS
Impaired EPC function may lead to accelerated vascular remodeling due to chronic impairment of endothelial maintenance.
Keymel
Stefanie
S
Medical Clinic I, Dept. of Medicine, Division of Cardiology, Pulmonology, and Vascular Medicine, RWTH University Hospital Aachen, Pauwelstrasse 30, 52074, Aachen, Germany.
Kalka
Christoph
C
Rassaf
Tienush
T
Yeghiazarians
Yerem
Y
Kelm
Malte
M
Heiss
Christian
C
D000328:Adult; D000375:Aging / Q000502:physiology*; D001161:Arteriosclerosis / Q000473:pathology* / Q000503:physiopathology*; D001794:Blood Pressure / Q000502:physiology; D002339:Carotid Arteries / Q000473:pathology* / Q000503:physiopathology; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D017539:Tunica Intima / Q000473:pathology* / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A