Abstract 968: Essential Role of Bone Marrow FGF2 in the Effect of Estradiol on Reendothelialization and EPC Mobilization
17b-estradiol (E2) accelerates reendothelialization and increases the number of circulating endothelial progenitor cells (EPCs), but whether a major growth factor, such as Fibroblast Growth Factor-2 (FGF2) is involved in these processes remains unknown. FGF2 is expressed as both a secreted low MW (lmw) isoform, and two intranuclear high MW (hmw) isoforms in mouse. The present study explored the role of FGF2 in the effect of E2 on reendothelialization and EPC levels in a mouse model. As previously reported, E2 increased both the velocity of reendothelialization and the number of circulating EPCs in ovariectomized wild type (Fgf2+/+) mice. In contrast, the effect of E2 on both parameters was abolished in mice deficient in FGF2 mice (Fgf2−/−), demonstrating that FGF2 is absolutely required for these effects of E2. E2 was found to slightly increase FGF2hmw levels in the aorta, and markedly increase both FGF2lmw and FGF2hmw in bone marrow (BM). To evaluate the specific role played by increased BM FGF2 expression in the effect of E2, we developed chimeric mice by grafting Fgf2−/−BM to Fgf2+/+ (Fgf2−/−BM => Fgf2+/+) mice and observed that the effect of E2 on both reendothelialization and EPC levels was abolished. In contrast, both effects of E2 in Fgf2+/+BM => Fgf2−/− mice were similar to those observed in Fgf2+/+ mice, demonstrating that only BM-derived, but not extramedullary, FGF2 is required for both effects. In conclusion, FGF2, and more specifically bone marrow FGF2, is necessary and sufficient to mediate the accelerative effect of E2 on both reendothelialization and EPC mobilization.