Abstract
BackgroundTo study the regenerative capacity of the endothelium in patients with coronary artery disease (CAD), we cultured blood outgrowth endothelial cells (BOECs) of patients with premature CAD and their first degree relatives (FDR). Additionally we evaluated the influence of statin treatment on circulating BOEC precursors in subjects with subclinical atherosclerosis.Methods and ResultsPatients with premature CAD (men <51 yr, women <56 yr) and their FDRs were included. Based on coronary calcification (CAC) scores FDRs were divided in a group of healthy subjects (CAC = 0) and subjects with subclinical atherosclerosis (CAC>0). We did not observe differences in the number of BOEC colonies and proliferation between premature CAD patients and FDRs. FDRs with subclinical atherosclerosis had lower colony numbers compared with healthy FDRs, however this was not statistically significant, and BOEC proliferation was significantly impaired (OR = 0.45, 95% CI 0.21–0.96). Unexpectedly, the number of BOEC colonies and BOEC proliferation were similar for premature CAD patients and healthy FDRs. Since a considerable number of premature CAD patients used statins, we studied the number of BOEC precursors as well as their proliferative capacity in ten individuals with subclinical atherosclerosis, before and after statin therapy. Interestingly, FDRs with subclinical atherosclerosis showed a significant increase in the number of BOEC colonies after statin therapy.ConclusionBOEC proliferation of subjects with subclinical atherosclerosis is impaired compared with healthy controls. In these subjects, statin therapy significantly increased the number of circulating BOEC precursors as well as their proliferative capacity, revealing a beneficial effect of statins on endothelial regeneration.
Highlights
Cardiovascular disease (CVD) represents a major health issue worldwide [1]
blood outgrowth endothelial cells (BOECs) proliferation of subjects with subclinical atherosclerosis is impaired compared with healthy controls
Statin therapy significantly increased the number of circulating BOEC precursors as well as their proliferative capacity, revealing a beneficial effect of statins on endothelial regeneration
Summary
Cardiovascular disease (CVD) represents a major health issue worldwide [1]. Endothelial dysfunction, resulting in atherosclerotic plaque formation and subsequent ischemia is the main underlying cause of this disease [2]. EPCs represent a heterogeneous population of circulating mononuclear cells [3], among which two distinct populations can be distinguished [7]: early endothelial progenitor cells (eEPCs) and blood outgrowth endothelial cells (BOECs), designated as endothelial colony forming cells (ECFCs) [8,9] Despite their late onset, BOECs display an enhanced proliferative capacity compared with eEPCs [8]. Comparative genetic and phenotypic analyses have firmly established that eEPCs display a genetranscription profile similar to cells of the hematopoietic lineage, whereas BOECs belong to the endothelial lineage This implies that the regenerative capacity of the endothelium is crucially dependent on the frequency of these ‘‘true EPCs’’ in the circulation [7,9,10]. We evaluated the influence of statin treatment on circulating BOEC precursors in subjects with subclinical atherosclerosis
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