Current perspective of pathophysiological and interventional effects on endothelial progenitor cell biology: Focus on Pi3K/AKT/eNOS pathway

For more than a decade, endothelial progenitor cells (EPCs) have been implicated in cardiovascular homeostasis. EPCs are believed to reside within the bone marrow in close contact with surrounding stromal cells, and, under stimulation of pro-inflammatory cytokines, EPCs are mobilized out of the bone marrow. Hereafter circulating EPCs home to peripheral tissues, undergoing further proliferation and differentiation. Under certain pathophysiologic conditions this process seems to be blunted, resulting in a reduced capacity of EPCs to engage in vasculogenesis at sites of endothelial injury or tissue ischemia. In this review, we focus on the effects of traditional cardiovascular risk factors on EPC biology and we explore whether pharmacological, dietary and lifestyle interventions can favorably restore EPC mobilization, differentation, homing and angiogenic properties. Because the PI3K/Akt/eNOS pathway plays a pivotal role in the process of EPC mobilization, migration and homing, we specifically emphasize the involvement of PI3K, Akt and eNOS in EPC biology under these different (patho)physiologic conditions. (Pre)clinically used drugs or lifestyle interventions that have been shown to ameliorate EPC biology are reviewed. These treatment strategies remain attractive targets to restore the regenerative capacity of EPCs in cardiovascular diseases.