Essential role of bone marrow fibroblast growth factor-2 in the effect of estradiol on reendothelialization and endothelial progenitor cell mobilization

Vincent Fontaine, Cédric Filipe, Nikos Werner, Pierre Gourdy, Audrey Billon, Barbara Garmy-Susini, Laurent Brouchet, Francis Bayard, Hervé Prats, Thomas Doetschman, Georg Nickenig, Jean François Arnal

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Abstract

17β-Estradiol (E2) accelerates reendothelialization and increases the number of circulating endothelial progenitor cells (EPCs), but whether fibroblast growth factor-2 (FGF2) is involved in these processes remains unknown. Here we 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 FGF2-deficient mice (Fgf2-/-), demonstrating that FGF2 is absolutely required for these effects of E2. To test the implication of medullary and extramedullary FGF2, we developed chimeric mice by grafting Fgf2-/- bone marrow to Fgf2+/+ [Fgf2-/- bone marrow (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. Interestingly, E2 was found to markedly increase both FGF2lmw and FGF2hmw in bone marrow. In conclusion, FGF2, specifically medullary FGF2, is necessary and sufficient to mediate the accelerative effect of E2 on both reendothelialization and EPC mobilization.

Original languageEnglish (US)
Pages (from-to)1855-1862
Number of pages8
JournalAmerican Journal of Pathology
Volume169
Issue number5
DOIs
StatePublished - Nov 2006
Externally publishedYes

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Fontaine, V., Filipe, C., Werner, N., Gourdy, P., Billon, A., Garmy-Susini, B., Brouchet, L., Bayard, F., Prats, H., Doetschman, T., Nickenig, G., & Arnal, J. F. (2006). Essential role of bone marrow fibroblast growth factor-2 in the effect of estradiol on reendothelialization and endothelial progenitor cell mobilization. American Journal of Pathology, 169(5), 1855-1862. https://doi.org/10.2353/ajpath.2006.060260