title: Impaired endothelial progenitor cell function predicts age-dependent carotid intimal thickening.
abstract: 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.
authors.affiliation: Medical Clinic I, Dept. of Medicine, Division of Cardiology, Pulmonology, and Vascular Medicine, RWTH University Hospital Aachen, Pauwelstrasse 30, 52074, Aachen, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Keymel
authors.forename: Christoph
authors.initials: C
authors.lastname: Kalka
authors.forename: Tienush
authors.initials: T
authors.lastname: Rassaf
authors.forename: Yerem
authors.initials: Y
authors.lastname: Yeghiazarians
authors.forename: Malte
authors.initials: M
authors.lastname: Kelm
authors.forename: Christian
authors.initials: C
authors.lastname: Heiss
mesh_terms: 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
chemical_list: D042461:Vascular Endothelial Growth Factor A