Age-dependent depression in circulating endothelial progenitor cells inpatients undergoing coronary artery bypass grafting

Scheubel, R.; Zorn, H; Silber, Rolf-Edgar; Kuß, Oliver; Morawietz, Henning; Holtz, Juergen; Simm, Andreas

doi:10.1016/j.jacc.2003.07.025

Cited by 331 publications

(251 citation statements)

References 42 publications

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“…One study showed that ''EPCs,'' defined only as CD133þ/CD34þ, decreased with aging in patients with CAD scheduled for coronary bypass surgery (18). Their findings are similar to ours for PCs; however, we used a more stringent definition of EPCs that included the VEGF-R2 receptor.…”

Section: Discussionsupporting

confidence: 73%

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: Discussionsupporting

confidence: 73%

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).…”

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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“…26,66,67 It has been reported that in young patients with stable coronary artery disease after coronary artery bypass grafting, the number of CEPCs increases, whereas the opposite occurs in older patients. 66 The age-related deficiency in the number of CEPCs was not related to differences in cardiovascular risk factor or cardiac function and it may be caused, at least in part, by reduced levels of angiogenic and mobilizing cytokines. This deficiency may be at the root of impaired neovascularization of ischemic tissues and attenuated re-endothelialization of injured tissues commonly observed in older patients.…”

Section: Epc and Agingmentioning

confidence: 99%

“…16,27,28,55,58,62,63 Aging and diabetes markedly reduce the availability and impair the function of EPCs. 28,[62][63][64]66,67 Because older and diabetic patients are the most vulnerable populations for cardiovascular diseases, this severely restricts the ability to treat with autologous EPCs the patients who theoretically need them most. The purity and developmental stage of the cells used for transplantation are important factors.…”

Section: Potential Problems With Therapeutic Use Of Epcsmentioning

confidence: 99%

Therapeutic Potential of Endothelial Progenitor Cells in Cardiovascular Diseases

et al. 2005

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Abstract-Endothelial dysfunction and cell loss are prominent features in cardiovascular disease. Endothelial progenitor cells (EPCs) originating from the bone marrow play a significant role in neovascularization of ischemic tissues and in re-endothelialization of injured blood vessels. Several studies have shown the therapeutic potential of EPC transplantation in rescue of tissue ischemia and in repair of blood vessels and bioengineering of prosthetic grafts. Recent small-scale trials have provided preliminary evidence of feasibility, safety, and efficacy in patients with myocardial and critical limb ischemia. However, several studies have shown that age and cardiovascular disease risk factors reduce the availability of circulating EPCs (CEPCs) and impair their function to varying degrees. In addition, the relative scarcity of CEPCs limits the ability to expand these cells in sufficient numbers for some therapeutic applications. Priority must be given to the development of strategies to enhance the number and improve the function of CEPCs. Furthermore, alternative sources of EPC such as chord blood need to be explored. Strategies for improvement of cell adhesion, survival, and prevention of cell senescence are also essential to ensure therapeutic viability. Genetic engineering of EPCs may be a useful approach to developing these cells into efficient therapeutic tools. In the clinical arena there is pressing need to standardize the protocols for isolation, culture, and therapeutic application of EPC. Large-scale multi-center randomized trials are required to evaluate the long-term safety and efficacy of EPC therapy. Despite these hurdles, the outlook for EPC-based therapy for cardiovascular disease is promising. (Hypertension. 2005;46:7-18.)

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Age-dependent depression in circulating endothelial progenitor cells inpatients undergoing coronary artery bypass grafting

Abstract: Despite a significant increase in EPCs and release of cytochemokines during CABG, age is a major limiting factor for mobilization of EPCs. Further studies are necessary to improve the strategies for mobilization, ex vivo expansion, and re-transplantation of EPCs in aging patients.

Cited by 331 publications

References 42 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

Therapeutic Potential of Endothelial Progenitor Cells in Cardiovascular Diseases

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