title: Individual with subclinical atherosclerosis have impaired proliferation of blood outgrowth endothelial cells, which can be restored by statin therapy.
abstract: BACKGROUND
  To 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.
  
  
  RESULTS
  Patients 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.
  
  
  CONCLUSIONS
  BOEC 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.
authors: Department of Plasma Proteins, Sanquin-AMC Landsteiner Laboratory, Amsterdam, The Netherlands.
authors: Javier
authors: J
authors: Martin-Ramirez
authors: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands; Department of Experimental Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors: Maayke G M
authors: MG
authors: Kok
authors: Department of Plasma Proteins, Sanquin-AMC Landsteiner Laboratory, Amsterdam, The Netherlands.
authors: Menno
authors: M
authors: Hofman
authors: Department of Plasma Proteins, Sanquin-AMC Landsteiner Laboratory, Amsterdam, The Netherlands.
authors: Ruben
authors: R
authors: Bierings
authors: The Heart Failure Research Center, Academic Medical Center, Amsterdam, The Netherlands.
authors: Esther E
authors: EE
authors: Creemers
authors: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands; Department of Experimental Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors: Joost C M
authors: JC
authors: Meijers
authors: Department of Plasma Proteins, Sanquin-AMC Landsteiner Laboratory, Amsterdam, The Netherlands.
authors: Jan
authors: J
authors: Voorberg
authors: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands; Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, The Netherlands.
authors: Sara-Joan
authors: SJ
authors: Pinto-Sietsma
mesh_terms: D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors