Brain derived neurotrophic factor is an endothelial cell survival factor required for intramyocardial vessel stabilization.
Brain derived neurotrophic factor is an endothelial cell survival factor required for intramyocardial vessel stabilization.
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发表时间：
2000-11
期刊：
影响因子：
4.6
通讯作者：
M. Donovan;Michelle I. Lin;P. Wiegn;T. Ringstedt;R. Kraemer;Rebecca T. Hahn;Shiyang Wang;C. Ibáñez
中科院分区：
文献类型：
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作者：
M. Donovan;Michelle I. Lin;P. Wiegn;T. Ringstedt;R. Kraemer;Rebecca T. Hahn;Shiyang Wang;C. Ibáñez
脑源性神经营养因子 (BDNF) 是一种神经营养蛋白，其特征在于其对表达 trk B 受体酪氨酸激酶的神经元的存活和分化作用。尽管 BDNF(-)(/)(- ) 小鼠中许多神经元丢失，但这些动物出生后早期的致死性表明该生长因子具有更广泛的功能。在这里，我们证明 BDNF 的表达缺陷会损害出生后早期心肌内动脉和毛细血管内皮细胞的存活，尽管胚胎脉管系统可以重塑为动脉、毛细血管和静脉。 BDNF 缺乏导致内皮细胞间接触减少和内皮细胞凋亡，导致心室内壁出血、心肌收缩力下降和产后早期死亡。血管出血仅限于心血管，反映了该血管床中毛细血管和小动脉局部表达 BDNF 和 trk B。相反，妊娠中期小鼠心脏中异位 BDNF 过度表达会导致毛细血管密度增加。此外，BDNF 激活内源性 trk B 受体可支持新生小鼠培养的心脏微血管内皮细胞的存活。这些结果确立了 BDNF 通过对内皮细胞的直接血管生成作用维持心脏血管稳定性的重要作用。
Brain derived neurotrophic factor, BDNF, is a neurotrophin best characterized for its survival and differentiative effects on neurons expressing the trk B receptor tyrosine kinase. Although many of these neurons are lost in the BDNF(-)(/)(- )mouse, the early postnatal lethality of these animals suggests a wider function for this growth factor. Here, we demonstrate that deficient expression of BDNF impairs the survival of endothelial cells in intramyocardial arteries and capillaries in the early postnatal period, although the embryonic vasculature can remodel into arteries, capillaries and veins. BDNF deficiency results in a reduction in endothelial cell-cell contacts and in endothelial cell apoptosis, leading to intraventricular wall hemorrhage, depressed cardiac contractility and early postnatal death. Vascular hemorrhage is restricted to cardiac vessels, reflecting the localized expression of BDNF and trk B by capillaries and arterioles in this vascular bed. Conversely, ectopic BDNF overexpression in midgestational mouse hearts results in an increase in capillary density. Moreover, BDNF activation of endogenous trk B receptors supports the survival of cardiac microvascular endothelial cells cultured from neonatal mice. These results establish an essential role for BDNF in maintaining vessel stability in the heart through direct angiogenic actions on endothelial cells.