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Circulating endothelial progenitor cells from healthy smokers exhibit impaired functional activities

      Abstract

      Objective

      : Endothelial dysfunction is one of the earliest pathological effects of cigarette smoking. It has recently been suggested that endothelial progenitor cells (EPCs) could contribute to ongoing endothelial maintenance and repair. Accordingly, we tested the hypothesis that cigarette smoking is associated with EPC dysfunction.

      Methods and results

      : EPCs were isolated from the peripheral venous blood of 15 healthy smokers and 11 age-matched nonsmokers. The number of EPCs was significantly reduced in smokers versus control subjects (51.6 ± 1.9 versus 120.3 ± 10.0 per power field, p < 0.001). Moreover, the functional activities of EPCs isolated from smokers were severely compromised. First, the proliferative and migratory response of EPCs isolated from smokers were reduced by 75% and 19%, respectively (p < 0.05). Second, EPCs from smokers showed an important decreased adherence to HUVECs that had been previously activated with tumor necrosis factor-α (TNF-α) (p < 0.01). Finally, the participation of EPCs to tube formation in a matrigel assay was reduced by 38% in smokers versus control subjects (p < 0.001). We found that EPCs from smokers had a significant reduction in the expression of the endothelial cell-specific markers (VE-cadherin, KDR, and vWF). Moreover, ROS formation was significantly increased in EPCs from smokers, whereas the serum antioxidant and nitrite levels of smokers were reduced and correlated with impaired EPC number and functional activity.

      Conclusions

      : Cigarette smoking is associated with a reduced number of EPCs together with an important impairment of EPC differentiation and functional activities. Our results suggest that EPC dysfunction could contribute to impair blood vessel healing and growth in smokers.

      Keywords

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