Abstract 4052: Women Differ from Men in the Contribution of Vascular Progenitor Cells to Endothelial Function and Cardiovascular Risk
Objective: Endothelial dysfunction has been implicated in the development of cardiovascular disease. Our group previously reported that in men without known cardiovascular disease, endothelial progenitor cell colony-forming units (EPC-CFU) are significantly related to both endothelial function and cardiovascular risk as measured by the Framingham Risk Score (FRS). We assessed the hypothesis that hormonal status may impact women’s EPC, vascular, and risk relationships.
Methods: We recruited 66 female subjects aged 22– 63 (mean ± SD = 43 ± 11) with no history of cardiovascular disease. Peripheral blood mononuclear cells were cultured in fibronectin-coated wells: EPC-CFU = cell clusters with endothelial outgrowth at 5 days. Endothelial function was determined by brachial artery flow-mediated dilation (% of resting diameter).
Results: Endothelial function was significantly associated (r = −0.39, p = 0.001) with cardiovascular risk derived from the FRS for women. In contrast to men, we found no significant relationship between EPC-CFU and either endothelial function (r = 0.008) or FRS (r = 0.003). Furthermore, we detected no relationship in women between EPC-CFU and total cholesterol, LDL cholesterol, or frequency of hypertension and diabetes; these variables were significantly related in our male cohort. To explore the potential confounding effects of estrogen on EPC-CFU and endothelial function in women, we partitioned our cohort by hormonal status based on the ratio of estradiol to follicle stimulating hormone (FSH). There was no relationship between EPC-CFU and estradiol/FSH, but endothelial function was significantly lower in women with the lowest estradiol/FSH compared to women with higher estradiol/FSH (p< 0.05). As expected, older women had lower estradiol/FSH than younger women (p< 0.001); however, within the tertiles of estradiol/FSH there was no relationship between endothelial function and age.
Conclusions: Endothelial function is associated with cardiovascular risk in women; however, in contrast to observations made in men, EPC-CFU are not a determinant of cardiovascular risk or endothelial function. Our data suggest that women’s hormonal status, independent of age, determines endothelial function and cardiovascular risk.