Androgens Stimulate EPC-Mediated Neovascularization and Are Associated with Increased Coronary Collateralization
Abstract
Endothelial progenitor cells (EPCs) play a key role in neovascularization and have been linked to improved cardiovascular outcomes. Although there is a well-established inverse relationship between androgen levels and cardiovascular mortality in men, the role of androgens in EPC function is not fully understood. In this study, we investigated the effects of androgens on two subpopulations of EPCs, early EPCs (EEPCs) and late outgrowth EPCs (OECs), and their relationship with coronary collateralization. EEPCs and OECs were isolated from the peripheral blood of young healthy men and treated with dihydrotestosterone (DHT) with or without androgen receptor (AR) antagonist, hydroxyflutamide, in vitro. DHT treatment enhanced AR-mediated proliferation, migration and tubulogenesis of EEPCs and OECs in a dose-dependent manner. Furthermore, DHT augmented EPC sensitivity to extracellular stimulation by vascular endothelial growth factor (VEGF) via increased surface VEGF receptor expression and AKT activation. In vivo, xenotransplantation of DHT pretreated human EPCs augmented blood flow recovery and angiogenesis in BALB/c nude male mice, compared to mice receiving untreated EPCs, following hindlimb ischemia. In particular, DHT pretreated ...Continue Reading
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