Key result
Older age linked to ~2-point lower flow-mediated dilation alongside impaired endothelial progenitor cells.
Why the study?
Human age-related endothelial dysfunction may be accompanied by quantitative and qualitative alterations of the endothelial progenitor cell pool, which could explain vascular changes with aging.
Does advanced age impair endothelial function and endothelial progenitor cell (EPC) pool activity in healthy individuals?
Cross-Sectional (n=20)
Does advanced age impair endothelial function and endothelial progenitor cell (EPC) pool activity in healthy individuals?
Absolute Event Rate: 5.2% vs 7.1%
p-value: p=<0.05
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Several authors have documented that bone marrow-derived EPCs from aged animals or humans are quantitatively reduced and dysfunctional, thus predisposing to atherosclerosis. This has important pathophysiological and therapeutic implications, because autologous EPCs are being used in cell therapy trials that often involve aging individuals.”
“According to this new theory, the arterial wall can deal fairly well with multiple circulating and local noxious stimuli, as long as the bone marrow-derived repair capacity, which includes competent EPCs and probably progenitors of other lineages, remains intact. Senescence of selected bone marrow pathways, a process that is accelerated by the passage of time in the presence of risk factors, can lead to the inability of the bone marrow to provide for adequate arterial repair.”
Age-related endothelial dysfunction is associated with functional deficits in endothelial progenitor cells (decreased survival, migration, and proliferation) rather than a depletion in their absolute numbers.
OBJECTIVES: 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.
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Heiß et al. (2005) conducted a cross-sectional in Healthy individuals without major cardiovascular risk factors (n=20). Older age vs. Young age was evaluated on Endothelium-dependent dilation of the brachial artery (flow-mediated dilation) (p=<0.05). Older age was associated with significantly impaired flow-mediated dilation (5.2% vs. 7.1%; P<0.05) and functional deficits in endothelial progenitor cells compared to young age.
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