Menstrual cycle influences endothelial progenitor cell regulation: A link to gender differences in vascular protection?

Background: The potential role of endothelial progenitor cells (EPCs) in the beneficial effects of estrogen on women's cardiovascular health is of great interest. We thus evaluated if menstrual cycle influences circulating levels of EPC subpopulations in normally menstruating women and if this could underline gender differences. Methods and results: Ten women and ten men were recruited for this study. Peripheral blood samples were collected at each menstrual cycle phase in women and, three times over a one month period in men. Flow cytometry analysis revealed that, in women, the number of CD133+/CD34-, CD133+/CD34+ progenitor cells (PCs) and CD133+/CD34+/VEGF-R2+ EPCs per ml of blood fluctuated significantly throughout the cycle in synchronization with the level of circulating 17 beta-estradiol (17 beta E). Maturation of CD133+/VEGF-R2+ and CD133+/CD34-/VEGF-R2+ EPCs towards respective CD144+ advanced EPC (aEPC) subpopulations was reduced at mid-luteal phase. Greater mean global number of CD133+/CD34+ PC, CD133+/VEGF-R2+ and CD133+/CD34-/VEGF-R2+ EPC subpopulations was found in women and 17 beta E was identified as a predictive factor for the gender differences perceived. Finally, maturation of CD133+ and CD133+/CD34- towards respective EPCs or aEPCs was increased in women compared to men. Conclusions: Our results suggest a physiological regulation of the availability of PC and EPC subpopulations in premenopausal women throughout menstrual cycle and reveal gender differences in the level and maturity of specific PC, EPC and aEPC subpopulations. This cyclic regulation in premenopausal women, may in part explain the lower prevalence of cardiovascular events at middle age compared with men or the timing of such events during the menstrual cycle. (c) 2008 Elsevier Ireland Ltd. All rights reserved.