ANTIOXIDANT CAPACITY OF CIRCULATING ENDOTHELIAL PROGENITOR CELLS (EPCS) AND CIGARETTE SMOKING

Endothelial progenitor cells (EPCs) have been suggested to contribute to ongoing endothelial maintenance and repair. Decreased levels of circulating EPCs associated with increased formation of oxygen reactive species (ROS) have been reported in smoker subjects, however, the effects of cigarette smoking (CS) on EPCs remain to be clarified. In the present study we investigated the effects of CS on the levels of ROS and expression of manganese superoxide dismutase (MnSOD), catalase (CAT) and glutathione peroxidase type 1 (GPX-1)-mRNA in EPCs isolated from peripheral blood of 36 healthy cigarette smokers and 26 nonsmokers controls. Furthermore, we valuated the relationship between circulating EPCs and the plasma levels of CRP and endogenously NO-derived product nitrite/nitrate. In smokers the expression of MnSOD-mRNA was significantly higher (p <0.001), whereas the expression of CAT and GPx-1-mRNA was lower (p<0.001) than controls. The amount of ROS was more elevated in smokers (p<0.001); by contrast the number of EPCs was reduced respect to controls (p<0.001). A strong correlation between circulating EPCs and levels of CRP (rs =0.939,p<0.001), fibrinogen (rs =0.632, p<0.001) and nitrite/nitrate (rs= 0.880,p<0.001) was observed. EPCs were also correlated with the amount of ROS (rs =0.832, p<0.001) and with the expression of MnSOD (rs =0.859,p<0.001), CAT (rs =0.926, p<0.001) and GPx-1 (rs =0.927, p<0.001) -mRNA. Moreover, significant correlations were observed between the levels of CRP, fibrinogen, nitrite/nitrate, and the expression of MnSOD (rs= 0.892, p<0.001; rs= 0.688, p<0.001; rs =0.821, p<0.001, respectively), CAT (rs =-0.907, p<0.001; rs =0.656, p<0.001; rs= 0.844, p<0.005, respectively), and GPx-1-mRNA (rs =0.863, p<0.001; rs =0.585, p<0.001; rs= 0.863, p<0.001). The correlation panel showed significant values between ROS and MnSOD-mRNA (rs= 0.827, p<0.001), and between ROS and both CAT (rs =0.795,p<0.001), and GPx-1 (rs= 0.745, p< 0.001). Additionally, dependence analysis indicated that CS influenced positively the levels of CRP (p<0.001), fibrinogen (p<0.001) and ROS (p<0.001) and negatively the levels of HDL-C (p<0.05) and nitrite/nitrate (p<0.001), according to the intensity of smoke exposure. Multivariate regression model for EPC, showed that circulating EPCs number depends on GPx-1 expression (p<0.001), CRP (p <0.001) and HDL-C (p<0.005) plasma concentrations. Taken together our findings provide evidence for a new effect of smoke exposure involving the expression of EPCs antioxidant enzymes. Furthermore, they indicate that in smokers the inflammatory state and molecules may play a role in modulating EPCs levels and antioxidant enzymes.