OBJECTIVETo investigate the potential role of caveolin-1 (CAV-1) on membrane estrogen receptor (mER) mediated proliferation of endothelial progenitor cells (EPCs).

METHODSBone marrow (BM)-derived EPCs were cultured. The proliferation of EPCs induced by estradiol (E₂)-BSA in the absence or presence of ICI 182, 780 (a pure ER inhibitor), MβCD and CAV-1 siRNA was determined by [³H]-thymidine incorporation. The expression of CAV-1 was detected by Western blot.

RESULTSProliferation of EPC peaked after 10(-8) mol/L E₂-BSA culture for 24 h (87.5% increase vs. control), and this effect could be inhibited by estrogen receptor blocker ICI 182, 780, indicating that mER-initiated membrane signaling pathways was involved in the proliferation effect of estrogen on EPC. Both cholesterol depletion and CAV-1 siRNA significantly attenuated E₂-BSA induced [³H]-thymidine incorporation. Western blot result confirmed that cholesterol depletion or CAV-1 siRNA significantly decreased CAV-1 protein expression (-18.6% or -41.2% vs. 10(-8) mol/L E₂-BSA alone).

CONCLUSIONOur results suggested that estradiol promoted EPC proliferation through activating CAV-1 pathway.