Osteocalcin positive CD133+/CD34-/KDR+ progenitor cells as an independent marker for unstable atherosclerosis

Abstract

For the characterization of endothelial progenitor cells (EPCs), commonly the markers CD34 and KDR have been used. CD133+/CD34-/KDR+ cells may represent more immature 'early' progenitors. In patients with coronary artery disease (CAD), a large fraction of EPCs carry the osteoblastic marker osteocalcin (OCN), which may mediate vascular calcification and abnormal repair. The aim of this study was to evaluate the expression of OCN+ 'early' EPCs in patients with risk factors (RFs) and a history of stable (history of stenting/coronary artery bypass grafting) or unstable CAD (myocardial infarction). Medical history and blood samples from 282 patients (age 58 ± 16 years) with CAD or at least one RF (mean 2.5 ± 1.5) were analysed. For the analysis of EPC markers (CD133, CD34, KDR) and OCN, the flow cytometry of peripheral blood mononuclear cells was performed. Circulating OCN+/CD133+/CD34-/KDR+ cells (median counts [interquartile range] per 100 000 events) were 15 [4-41] in patients with RF (n = 199), 26 [1-136] in those with a history of stable (n = 57), and 246 [105-308] in those with a history of unstable CAD (n = 26; P < 0.001). The association with unstable CAD remained highly significant even after multivariate adjusting for RFs and the different characteristics of the groups. Osteocalcin positive 'early' EPCs trend to predict further events [HR for each doubling of the cell number: 1.20 (95% CI: 1.00-1.46), P = 0.06]. Circulating OCN+ 'early' EPCs are strongly associated with unstable CAD. Therefore, this particular subset of EPCs could mediate abnormal vascular repair and may help identifying patients with a more unstable phenotype of atherosclerosis.