Impaired myocardial capillarogenesis and increased adaptive capillary growth in FGF2-deficient mice

Impaired myocardial capillarogenesis and increased adaptive capillary growth in FGF2-deficient mice
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DOI:
10.1038/labinvest.3700359
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发表时间:
2006-01-01
影响因子:
5
通讯作者:
Ehmke, H
Ehmke, H
中科院分区:
医学2区
文献类型:
--
作者:
Amann, K;Faulhaber, J;Ehmke, H

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碱性成纤维细胞生长因子(FGF2)在血管生成和毛细血管生长中起主要作用。与内皮细胞增殖和存活所需的血管内皮生长因子相比,FGF2 似乎不是必需的,因为 Fgf2 敲除并不致命。因此,FGF2 对毛细血管发育和适应的精确遗传和生理作用仍有待确定。在这里,我们发现,出生时心肌毛细血管供应正常,但与野生型同窝小鼠相比,成年 Fgf2(+/-) 和 Fgf2(-/-) 小鼠的心肌毛细血管供应显着减少约 25%。相比之下,通过连续输注血管紧张素II (ANG II) 6天诱导心肌肥大后,在Fgf2(+/-)和Fgf2(-/-)小鼠中均观察到显着的毛细血管生长,但在野生型同窝小鼠中未观察到。这些数据表明,两个完整的Fgf2基因对于出生后正常毛细血管发育是必需的,而FGF2对于成年小鼠的适应性心肌毛细血管生长似乎是可有可无的。
Basic fibroblast growth factor (FGF2) plays a major role in angiogenesis and capillary growth. In contrast to vascular endothelial growth factor, which is required for proliferation and survival of endothelial cells, FGF2 does not seem to be essential since the Fgf2 knockout is not lethal. Therefore, the precise genetic and physiological roles of FGF2 for capillary development and adaptation remain to be determined. Here we show that myocardial capillary supply is normal at birth, but significantly reduced by similar to 25% in adult Fgf2(+/-) and Fgf2(-/-) mice as compared with wild-type littermates. In contrast, after induction of myocardial hypertrophy by continuous infusion of angiotensin II (ANG II) for 6 days marked capillary growth was seen in both Fgf2(+/-) and Fgf2(-/-) mice, but not in wild-type littermates. These data demonstrate that two intact Fgf2 genes are necessary for normal capillary development after birth, whereas FGF2 seems to be dispensable for adaptive myocardial capillary growth in the adult mouse.