Affirmative action of osteopontin on endothelial progenitors.

Gender differences in susceptibility to coronary heart disease have been firmly established: the incidence of various manifestations of coronary atherosclerosis is less in premenopausal women than age-matched men. The protective role of estrogen covers a broad range of mechanisms including improvement of endothelial regeneration after arterial injury. Mediated primarily by the estrogen receptor alpha (ER ), 17 estradiol (E2) stimulates migration and proliferation of endothelium. This effect involves among others, eNOS activity,1 prostacyclin, endothelin, bFGF,2 and VEGF-R2 signaling.3 Estrogen also stimulates the recruitment of endothelial progenitor cells (EPCs), which in experimental and emerging clinical studies appear to be important effectors of endothelium repair (for review see Besler et al4). In rodents, E2 increases the number of circulating EPCs and enhances their adherence and homing to the region of vascular damage. This process is ER dependent and EPCs are believed to play a nonredundant role in the E2 enhanced reendothialization.1 Likewise, in premenopausal women a higher number of circulating EPCs is found when compared to age-matched men. The level of circulating EPCs synchronizes with menstrual cycle and is the highest during the fertile period. In addition, male EPCs showed a lower adherence capacity as compared to premenopausal female EPCs, an effect that was abolished by E2 supplementation.5