Elevated vascular endothelial cell growth factor affects mesocardial morphogenesis and inhibits normal heart bending
Elevated vascular endothelial cell growth factor affects mesocardial morphogenesis and inhibits normal heart bending
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DOI：
10.1002/dvdy.20539
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发表时间：
2006-01-01
影响因子：
2.5
通讯作者：
Little, CD
中科院分区：
文献类型：
--
作者：
Drake, CJ;Wessels, A;Little, CD
通过血管内皮细胞生长因子（VEGF）及其受体（VEGFRs）的信号传导是心血管发育所必需的。为了研究VEGF/VEGFR受体信号传导如何影响早期内皮细胞行为，使胚胎鹌鹑心脏经受升高的VEGF（165）水平（5 - 9体节阶段）。与未处理胚胎的心脏相比，显微注射重组人（rh）VEGF（165）的原始胚胎心脏表现出几种不同的畸形：内膜管畸形，具有扭曲的索和褶皱，被减少的心胶腔包围，受影响心脏的管腔明显减少。此外，胚胎心脏无法正常循环。弯曲的抑制伴随着背侧系膜的明显失效。萎缩-这被认为是心脏弯曲的必要条件。而不是萎缩，VEGF治疗的心内膜表现出显着增加的居民内皮细胞的数量。总的来说，这些数据表明，VEGF治疗的心脏中异常强大的心内膜阻碍了正常心脏弯曲所需的机械变形。我们的结论是，过度的VEGF信号传导最终在一个物理或生物力学机制，作用于广泛的，组织水平，长度尺度，导致严重的发育缺陷，心脏弯曲衰竭。
Signaling by means of vascular endothelial cell growth factor (VEGF) and its receptors (VEGFRs) is required for cardiovascular development. To examine how VEGF/VEGFR receptor signaling affects early endocardial cell behavior, embryonic quail hearts were subjected to elevated VEGF(165) levels (five- to nine-somite stage). Primitive embryonic hearts microinjected with recombinant human (rh)VEGF(165) exhibit several distinct malformations compared with hearts in untreated embryos: the endocardial tube is malformed with tortuous cords and folds surrounded by a diminished cardiac jelly space, and the lumens of affected hearts are conspicuously reduced. Furthermore, the embryonic heart fails to loop properly. Inhibition of bending is accompanied by an apparent failure of the dorsal mesocardium. to atrophy-an event thought to be necessary for heart bending. Instead of atrophy, VEGF-treated mesocardia exhibit a marked increased in the number of resident endothelial cells. Collectively, the data suggest that the abnormally robust mesocardia in VEGF-treated hearts impede the mechanical deformation required for normal heart bending. We conclude that the excessive VEGF signaling culminates in a physical or biomechanical mechanism that acts over a wide, tissue-level, length scale to cause a severe developmental defect-failure of heart bending.