Effect of smoking cessation on the number and adhesive properties of early outgrowth endothelial progenitor cells

Abstract

Background: Endothelial progenitor cells participate in angiogenesis and vascular repair, and cardiovascular risk factors may reduce their numbers or impair their functional properties. Cigarette smoking is a leading cause of preventable cardiovascular death, however, the functional properties of these cells before and after discontinuation of tobacco use have not been systematically analyzed. Methods: We examined changes in the number and function of early outgrowth endothelial progenitor cells (EPC), isolated from individuals (n = 144; mean age, 47.8 +/- 12.0 years; 43% males; more than 50% with additional cardiovascular risk factors or disease) who successfully completed a 5-week smoking cessation (SC) programme. Results: SC significantly reduced total white blood cell count (WBC; P<0.0001), plasma LDL cholesterol (P = 0.0002) and fibrinogen (P<0.0001) levels, but did not alter the number of circulating CD34(+), VEGFR2(+) or CD34(+), CD133(+) cells (P=0.14 and 0.57, respectively). Fewer acLDL(+), lectin(+) cells could be expanded from peripheral blood mononuclear cells in comparison to baseline (P<0.001). Furthermore, SC was associated with reduced EPC adhesion to fibronectin (P<0.001) or TNF alpha-activated endothelial cells (P=0.003), and a diminished incorporation of EPC into endothelial cell networks (P=0.035). Mechanistically, significantly reduced beta 1- and beta 2-integrin expression (P<0.001 and 0.007) and lower contents of intracellular reactive oxygen species (P<0.007) were detected in EPC following SC, in addition to reduced plasma asymmetric dimethyl-L-arginine (ADMA) levels (P=0.0003). Conclusions: Our findings suggest that the oxidative and inflammatory stress reduction associated with smoking cessation impair the adhesiveness of monocyte-derived EPC. (C) 2010 Published by Elsevier Ireland Ltd.