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

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 TNFα-activated endothelial cells (P = 0.003), and a diminished incorporation of EPC into endothelial cell networks (P = 0.035). Mechanistically, significantly reduced β1- and β2-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.