Impaired progenitor cell activity in age-related endothelial dysfunction
Open accessAbstract
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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Endothelial function is impaired in CAD patients who have reached blood pressure and LDL treatment goals compared with age-matched controls without cardiovascular risk factors.
“Despite the fact that our current patient population was medicated in accordance with current evidence-based standards, having reached their BP and LDL treatment goals, endothelial function was impaired as compared with age-matched controls without cardiovascular risk factors (8).”
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- Authors
- Heiss, C., Keymel, S., Niesler, U., Ziemann, J., Kelm, M., & Kalka, C.
- Affiliations
- Heinrich Heine University Düsseldorf (DE)
- Corresponding author
- Kalka, Christoph
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2005-05
- Volume
- 45
- Issue
- 9
- Pages
- 1441-1448
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W1966780233
- Cited by
- 573
- References
- 45
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 11 · 2023: 16 · 2022: 11 · 2021: 14 · 2020: 23 · 2019: 16 · 2018: 24 · 2017: 19 · 2016: 22 · 2015: 29 · 2014: 31 · 2013: 31 · 2012: 40
- FWCI
- 16.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- RWTH Publications (RWTH Aachen) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft ((SFB 612)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- endothelial progenitor cells, endothelial dysfunction, aging, flow-mediated dilation, EPC migration, EPC proliferation, vascular homeostasis, CD34+/KDR+ cells, endothelial repair, re-endothelialization, endothelial function, brachial artery, peripheral blood progenitor cells
- MeSH terms
- AC133 Antigen, Adult, Aging, Blood Flow Velocity, Brachial Artery, Cell Movement, Coronary Artery Disease, Endothelium, Vascular, Female, Glycoproteins, Humans, Male, Middle Aged, Peptides, Pulsatile Flow, Ultrasonography, Antigens, CD, Antigens, CD34, Vascular Endothelial Growth Factor A
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