Fontaine Vincent, Filipe Cédric, Werner Nikos, Gourdy Pierre, Billon Audrey, Garmy-Susini Barbara, Brouchet Laurent, Bayard Francis, Prats Hervé, Doetschman Thomas, Nickenig Georg, Arnal Jean-François
INSERM U589, Institut L. Bugnard, Centre Hospitalier Universitaire Rangueil, Toulouse Cedex, France.
Am J Pathol. 2006 Nov;169(5):1855-62. doi: 10.2353/ajpath.2006.060260.
17beta-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 FGF2(lmw) and FGF2(hmw) 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.
17β-雌二醇（E2）可加速血管再内皮化并增加循环内皮祖细胞（EPC）的数量，但成纤维细胞生长因子2（FGF2）是否参与这些过程尚不清楚。在此，我们在小鼠模型中探讨了FGF2在E2对血管再内皮化和EPC水平影响中的作用。如先前报道，E2可提高去卵巢野生型（Fgf2+/+）小鼠的血管再内皮化速度和循环EPC数量。相比之下，E2对这两个参数的影响在FGF2缺陷小鼠（Fgf2-/-）中消失，表明FGF2是E2产生这些效应所绝对必需的。为了测试骨髓和髓外FGF2的作用，我们通过将Fgf2-/-骨髓移植到Fgf2+/+[Fgf2-/-骨髓（BM）=＞Fgf2+/+]小鼠中培育出嵌合小鼠，并观察到E2对血管再内皮化和EPC水平的影响均消失。相反，E2在Fgf2+/+BM=＞Fgf2-/-小鼠中的这两种效应与在Fgf2+/+小鼠中观察到的相似，表明这两种效应仅需要骨髓来源而非髓外的FGF2。有趣的是，发现E2可显著增加骨髓中FGF2（低分子量）和FGF2（高分子量）的水平。总之，FGF2，特别是骨髓FGF2，对于介导E2对血管再内皮化和EPC动员的加速作用是必要且充分的。
