Abstract
PurposeOsteocalcin (OC), an osteoblast-derived regulator of metabolic processes, and circulating early endothelial progenitor cells (EPC, CD34 − /CD133 + /KDR +) expressing OC (OC +) are potential candidates linking bone metabolism and the vasculature and might be involved in vascular atherosclerotic calcification. This study aimed at assessing the association of circulating levels of different OC forms and of EPCs count with disease severity in patients with documented coronary atherosclerosis (CAD).MethodsPatients (n = 59) undergoing coronary angiography were divided, according to stenosis severity, into (1) early coronary atherosclerosis (ECA) (n = 22), and (2) late coronary atherosclerosis (LCA) (n = 37). Total OC (TOC), carboxylated OC (cOC), undercarboxylated OC (unOC) were quantified by ELISA. EPC OC + count was assessed by flow cytometry.ResultsEPC OC + counts showed significant differences between ECA and LCA groups. unOC and unOC/TOC ratio were inversely correlated with EPC OC + count. A significant decrease in TOC and unOC plasma levels was associated with higher cardiovascular risk factors (CVRFs) number. EPC OC + count was correlated with LDL-C, total cholesterol, and triglycerides, with a greater significance in the LCA group. No association between the different forms of circulating OC (TOC, ucOC, cOC) and severity of CAD was found.ConclusionThis study showed a significant association between EPCs (CD34 − /CD133 + /KDR + /OC +), CAD severity and CVRFs, suggesting an active role for EPC OC + in the development of CAD. An inverse correlation between TOC, ucOC, and number of CVRFs was observed, suggesting that OC, regardless of its carboxylation status, may be developed as a further cardiovascular risk biomarker.
Highlights
Atherosclerosis is associated with different risk factors, leads to vascular injury and, in conjunction with thrombosis, is the common cause of coronary artery disease (CAD)
late coronary atherosclerosis (LCA) and early coronary atherosclerosis (ECA) groups did not differ according to incidence of smoking, total cholesterol (TC), HDL-C, LDL cholesterol (LDL-C) and TG
We found that endothelial progenitor cells (EPCs) OC + counts correlated with increasing number of cardiovascular risk factors (CVRFs), a finding that supports the active role of EPC OC + in developing atherosclerosis
Summary
Atherosclerosis is associated with different risk factors, leads to vascular injury and, in conjunction with thrombosis, is the common cause of coronary artery disease (CAD). Clinical studies suggest a more complex role for OC in human metabolism, which led to investigations exploring its associations with CV disease (CVD) [19,20,21,22], and to clarify whether OC is a vital mediator or a nonparticipant bystander in energy metabolism and vascular function [23,24,25] Another candidate potentially providing a link between bone metabolism and CVD are endothelial progenitor cells (EPCs), which are nucleated bone marrow-derived cells, that can be mobilized in response to vascular injury, and contribute to vascular repair [26, 27]. That examined OC-positive endothelial progenitor cells (EPCs) or performed histological staining for OC, reported that higher OC levels were associated with an increase of markers of atherosclerosis and calcification [28, 29], possibly indicating that these OC-positive EPCs are a promising biomarker for severity stratification of CAD [30]
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