Impaired Progenitor Cell Activity in Age-Related Endothelial Dysfunction

Heiß, Christian; Keymel, Stefanie; Niesler, Ulrike; Ziemann, Jutta; Kelm, Malte; Kalka, Christoph

doi:10.1016/j.jacc.2004.12.074

Cited by 516 publications

(387 citation statements)

References 39 publications

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“…Their findings are similar to ours for PCs; however, we used a more stringent definition of EPCs that included the VEGF-R2 receptor. Another study, however, showed no differences in the numbers of circulating EPCs, defined as CD34/VEGF-R2 or CD133/VEGF-R2 double-positive cells in peripheral blood but there was lower survival, migration, and proliferation implicating functional impairment of EPCs from older subjects (19).…”

Section: Discussionmentioning

confidence: 93%

Flow cytometric measurement of circulating endothelial cells: The effect of age and peripheral arterial disease on baseline levels of mature and progenitor populations

Shaffer

Greene

Arshi

et al. 2006

Cytometry Part B Clinical

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Methods: Blood was collected from young healthy subjects (N = 9, mean age 33 6 8 years), older healthy subjects (N = 13, mean age 66 6 8 years), and older subjects with PAD (N = 15, mean age 69 6 8 years). After ammonium chloride lysis, cells were stained and analyzed on a Becton-Dickinson LSR II with a 5-color antibody panel: FITC-anti-CD31, PE-anti-CD146, PE-anti-CD133, PerCP-Cy5.5-anti-CD3, -CD19,-CD33 (lineage panel), PE-Cy7-anti-CD34, and APC-anti-VEGF-R2. Viability was assessed by propidium iodide exclusion, and only viable, low to medium side scatter lineage-negative singlets were analyzed. In some studies, cells were sorted for morphological studies. Subsets were defined as indicated later.Results: Our results, using a comprehensive flow cytometric panel, indicate that CD133+, CD34+, and CD133+/CD34+ PCs are elevated in younger healthy individuals compared to older individuals, both healthy and with PAD. However, the number of EPCs and mature ECs did not significantly differ among the three groups. Assessment of endothelial colony forming units and dual acLDL-lectin staining supported the flow cytometric findings.Conclusions: We describe a comprehensive flow cytometric method to detect circulating mature and progenitor endothelial populations confirmed by conventional morphological and functional assays. Our findings suggest that aging may influence circulating levels of PCs, but not EPCs or ECs; PAD had no effect on baseline levels of any populations investigated. This study provides the basis for evaluating the potential effects of acute stress and therapeutic intervention on circulating progenitor and endothelial populations as a biomarker for cardiovascular status. q

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Section: Discussionmentioning

confidence: 93%

Flow cytometric measurement of circulating endothelial cells: The effect of age and peripheral arterial disease on baseline levels of mature and progenitor populations

Shaffer

Greene

Arshi

et al. 2006

Cytometry Part B Clinical

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“…Deficiency in function and number of EPCs is associated with endothelial dysfunction (Scheubel et al, 2003;Heiss et al, 2005;Tao et al, 2006;Hoetzer et al, 2007). The data reported here showed that endothelial function measured by flow-mediated vasodilation in the brachial artery as well as in vitro SDF-1-induced migration and TNF-astimulated adhesion to HUVECs was markedly impaired in elderly men compared with young men, similar with prior reports (Taddei et al, 1995;Tao et al, 2004;Heiss et al, 2005;Hoetzer et al, 2007). Moreover, reendothelialization capacity of in vivo EPCs derived from elderly men was significantly reduced in a nude mouse carotid artery injury model.…”

Section: Discussionmentioning

confidence: 99%

Physical exercise attenuates age‐associated reduction in endothelium‐reparative capacity of endothelial progenitor cells by increasing CXCR4/JAK‐2 signaling in healthy men

Xia¹,

Li²,

Su³

et al. 2011

Aging Cell

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SummaryEndothelial progenitor cells (EPCs) play an important role in repairing endothelial injury. Aging is associated with EPC dysfunction. Physical exercise has a beneficial impact on EPC activity. However, whether physical exercise can enhance the endothelial repair capacity of EPCs in healthy men with aging is not clear. Here, we investigated the effects of physical exercise on reendothelialization capacity and CXC chemokine receptor four (CXCR4) signaling in human EPCs. Before and after 12-week exercise, EPCs were isolated from elderly and young men. In vitro function and in vivo reendothelialization capacity of EPCs in a mouse model of carotid artery injury were measured. The expression of CXCR4 and its downstream signaling target Janus kinase-2 (JAK-2) were determined. Before exercise, in vitro function and in vivo reendothelialization capacity of EPCs were significantly reduced in elderly men compared with young men. After exercise intervention, in vitro function and in vivo reendothelialization capacity of EPCs from elderly men were markedly enhanced. Physical exercise increased a higher CXCR4 protein expression and higher JAK-2 phosphorylation levels of EPCs. The augmentation in reendothelialization capacity of EPCs was closely correlated with the upregulation of CXCR4 ⁄ JAK-2 signaling and improvement of endothelial function. This study demonstrates for the first time that physical exercise attenuates age-associated reduction in endotheliumreparative capacity of EPCs by increasing CXCR4 ⁄ JAK-2 signaling. Our findings provide insight into the novel mechanisms of physical exercise as a lifestyle intervention strategy to promote vascular health in aging population.

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“…Traditional cardiovascular risk factors are diverse and include smoking, aging (29), hypercholesterolemia, hypertension, hyperglycemia (30), and a family history of premature atherosclerotic disease. All of those risk factors are associated with attenuation͞ loss of endothelium-dependent vasodilation.…”

Section: Effects Of Flavanol-rich Foods On Vascular Function and No Smentioning

confidence: 99%

(–)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans

Schroeter

Heiß

Balzer

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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937

825

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Impaired Progenitor Cell Activity in Age-Related Endothelial Dysfunction

Abstract: 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.

Cited by 516 publications

References 39 publications

Flow cytometric measurement of circulating endothelial cells: The effect of age and peripheral arterial disease on baseline levels of mature and progenitor populations

Flow cytometric measurement of circulating endothelial cells: The effect of age and peripheral arterial disease on baseline levels of mature and progenitor populations

Physical exercise attenuates age‐associated reduction in endothelium‐reparative capacity of endothelial progenitor cells by increasing CXCR4/JAK‐2 signaling in healthy men

(–)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans

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