Osteocalcin Expression by Circulating Endothelial Progenitor Cells in Patients With Coronary Atherosclerosis

OBJECTIVES To test whether patients with coronary atherosclerosis have increases in circulating endothelial progenitor cells (EPCs) expressing an osteogenic phenotype. BACKGROUND Increasing evidence indicates a link between bone and the vasculature, and bone marrow and circulating osteogenic cells have been identified by staining for the osteoblastic marker, osteocalcin (OCN). EPCs contribute to vascular repair, but repair of vascular injury may result in calcification. Using cell surface markers (CD34, CD133, KDR) to identify EPCs, we examined whether patients with coronary atherosclerosis had increases in the percentage of EPCs expressing OCN. METHODS We studied 72 patients undergoing invasive coronary assessment: Controls (normal coronary arteries and no endothelial dysfunction, n = 21) versus two groups with coronary atherosclerosis: early coronary atherosclerosis (ECA: normal coronary arteries but with endothelial dysfunction, n = 22) and late coronary atherosclerosis (LCA: severe, multi-vessel coronary artery disease [CAD], n = 29). Peripheral blood mononuclear cells were analyzed using flow cytometry. RESULTS Compared to controls, patients with ECA or LCA had significant increases (~2-fold) in the percentage of CD34+/KDR+ and CD34+/CD133+/KDR+ cells co-staining for OCN; even larger increases were noted in the ECA and LCA patients in the percentage of CD34+/CD133−/KDR+ cells co-staining for OCN (5- and 2-fold, P < 0.001 and 0.05, respectively). CONCLUSIONS A higher percentage of EPCs express OCN in patients with coronary atherosclerosis compared with subjects with normal endothelial function and no structural CAD. These findings have potential implications for the mechanisms of vascular calcification and for the development of novel markers for coronary atherosclerosis.