Abstract 721: Expression of Osteocalcin by Circulating Endothelial Progenitor Cells Predicts Endothelial Dysfunction or Structural Coronary Artery Disease
Objective: To test whether patients with coronary atherosclerosis (CAD) had increases in circulating endothelial progenitor cells (EPCs) expressing an osteogenic phenotype.
Background: EPCs contribute to vascular repair following vascular injury and may result in calcification supporting a link between bone and the vasculature. Bone marrow as well as circulating cells with osteogenic potential have been identified by staining for the osteoblastic marker, osteocalcin (OCN).
Methods and Results: 59 patients undergoing coronary angiography and assessment of coronary endothelial function by intracoronary administration of acetylcholine were studied. Subjects were defined as controls (no significant structural coronary lesions, normal endothelial function (n = 11) versus two groups with CAD: early CAD (eCAD, no significant structural coronary lesions but abnormal endothelial function, n = 19) and late CAD (lCAD, severe, multi-vessel CAD, n = 29). Peripheral blood mononuclear cells were analyzed using flow cytometry following staining for EPC markers (CD133, CD34, vascular endothelial growth factor receptor 2/kinase insert domain receptor [KDR]) and OCN (Table⇓). In unadjusted logistic regression models, a doubling of these OCN positive EPCs was associated with an odds ratio (OR) of 1.8 (95% confidence interval, 1.2–2.7) for having eCAD or lCAD; following adjustment for age, sex, and statin use, the corresponding OR was 4.2 (1.5–12.1); by comparison, the analogous OR for the currently used marker for CAD, high sensitivity C-reactive protein, were 0.9 (0.7–1.3) and 1.2 (0.7–1.9), unadjusted and age, sex, and statin use adjusted, respectively.
Conclusions: A higher percentage of EPCs co-stains for OCN in patients with CAD as compared to subjects with normal endothelial function and no structural CAD. These findings have potential implications for the mechanisms of EPCs in vascular calcification and for the development of novel markers for coronary disease.