Impaired progenitor cell activity in age-related endothelial dysfunction.
OBJECTIVE
We investigated whether human age-related endothelial dysfunction is accompanied by quantitative and qualitative alterations of the endothelial progenitor cell (EPC) pool.


BACKGROUND
Circulating progenitor cells with an endothelial phenotype contribute to the regeneration and repair of the vessel wall. An association between the loss of endothelial integrity and EPC modification may provide a background to study the mechanistic nature of such age-related vascular changes.


METHODS
In 20 old and young healthy individuals (61 +/- 2 years and 25 +/- 1 year, respectively) without major cardiovascular risk factors, endothelial function, defined by flow-mediated dilation of the brachial artery via ultrasound, as well as the number and function of EPCs isolated from peripheral blood, were determined.


RESULTS
Older subjects had significantly impaired endothelium-dependent dilation of brachial artery (flow-mediated dilation [FMD] 5.2 +/- 0.5% vs. 7.1 +/- 0.6%; p < 0.05). Endothelium-independent dilation after glycerol trinitrate (GTN) was not different, but the FMD/GTN ratio was significantly lower in old subjects (49 +/- 4% vs. 37 +/- 3%; p < 0.05), suggesting endothelial dysfunction. There were no differences in the numbers of circulating EPCs, defined as CD34/KDR or CD133/KDR double-positive cells in peripheral blood. In contrast, lower survival (39 +/- 6 cells/mm(2) vs. 65 +/- 11 cells/mm(2); p < 0.05), migration (80 +/- 12 vs. 157 +/- 16 cells/mm(2); p < 0.01), and proliferation (0.20 +/- 0.04 cpm vs. 0.44 +/- 0.07 cpm; p < 0.05) implicate functional impairment of EPCs from old subjects. The FMD correlated univariately with EPC migration (r = 0.52, p < 0.05) and EPC proliferation (r = 0.49, p < 0.05). Multivariate analysis showed that both functional features represent independent predictors of endothelial function.


CONCLUSIONS
Maintenance of vascular homeostasis by EPCs may be attenuated with age based on functional deficits rather than depletion of CD34/KDR or CD133/KDR cells.
Heiss
Christian
C
Department of Cardiology, Pneumology, and Vascular Medicine, Heinrich-Heine-University, Düsseldorf, Germany.
Keymel
Stefanie
S
Niesler
Ulrike
U
Ziemann
Jutta
J
Kelm
Malte
M
Kalka
Christoph
C
D000071916:AC133 Antigen; D000328:Adult; D000375:Aging; D015703:Antigens, CD; D018952:Antigens, CD34 / Q000032:analysis; D001783:Blood Flow Velocity; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000502:physiology*; D002465:Cell Movement; D003324:Coronary Artery Disease / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000503:physiopathology*; D005260:Female; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000032:analysis; D011673:Pulsatile Flow; D014463:Ultrasonography; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D042461:Vascular Endothelial Growth Factor A