The discovery of circulating adult progenitor cells (CPCs) capable of vascular repair has altered our conception of atherosclerosis from an inexorably progressive disease to one represented by a balance between vascular damage and repair. The numbers of CPCs has been correlated with risk factors for atherosclerosis, the extent of coronary artery disease, and with clinical outcomes; nonetheless, the measurement of CPCs in peripheral blood samples remains difficult. Multiple assays and techniques for enumerating CPCs have been reported, with minimal agreement between studies. We propose to investigate the numbers of CPCs in patients undergoing cardiac catheterization using a previously described assays based on cell surface expression of CD 133 and CD34, representative of late outgrowth endothelial progenitors, expression of CD13 and VEGFR-2, representative of early endothelial progenitors, and compare these progenitors with those identified using an assay of aldehyde dehydrogenase (ALDH) activity. We will rigorously assess the reproducibility and precision of both assays. We will then determine the correlation between CPCs enumerated using each technique with cardiac risk factors, extent of coronary disease, and clinical outcomes. Finally, we will study CPC mobilization using each technique in patients undergoing coronary artery bypass grafting, and compare CPC numbers and CPC mobilization with bone marrow progenitor cell content. By delineating the performance characteristics of these tests as well as determining the correlation of each with clinical factors, this work will delineate the role of CPC assessment for prognostic purposes. Our study in CABG patients will be the first to directly correlate not only baseline, but mobilized CPC levels with bone marrow progenitor cell content, and will offer important insights into mechanisms of progenitor cell depletion. Loss of adult stem cells capable of repairing blood vessels may be one explanation for the development of heart disease. This study will look at two methods of measuring these stem cells in the blood of heart patients. These methods may someday be used to predict who will or will not develop heart disease or other complications.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
The Career Enhancement Award (K18)
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Special Emphasis Panel (ZHL1-CSR-K (M2))
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Werner, Ellen
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Duke University
Internal Medicine/Medicine
Schools of Medicine
United States
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Povsic, Thomas J; Sloane, Richard; Green, Jennifer B et al. (2013) Depletion of circulating progenitor cells precedes overt diabetes: a substudy from the VA enhanced fitness trial. J Diabetes Complications 27:633-6
Povsic, Thomas J; Zhou, Jiying; Adams, Stacie D et al. (2010) Aging is not associated with bone marrow-resident progenitor cell depletion. J Gerontol A Biol Sci Med Sci 65:1042-50
Lou, Junyang; Povsic, Thomas J; Allen, Jason D et al. (2010) The effect of aspirin on endothelial progenitor cell biology: preliminary investigation of novel properties. Thromb Res 126:e175-9
Povsic, Thomas J; Adams, Stacie D; Zavodni, Katherine L et al. (2009) Aldehyde dehydrogenase activity allows reliable EPC enumeration in stored peripheral blood samples. J Thromb Thrombolysis 28:259-65
Povsic, Thomas J; Zavodni, Katherine L; Vainorius, Enrikas et al. (2009) Common endothelial progenitor cell assays identify discrete endothelial progenitor cell populations. Am Heart J 157:335-44
Povsic, Thomas J; Zavodni, Katherine L; Kelly, Francine L et al. (2007) Circulating progenitor cells can be reliably identified on the basis of aldehyde dehydrogenase activity. J Am Coll Cardiol 50:2243-8