Drake Christopher J, Wessels Andy, Trusk Tom, Little Charles D
Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, South Carolina, USA.
Dev Dyn. 2006 Jan;235(1):10-8. doi: 10.1002/dvdy.20539.
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 VEGF165 levels (five- to nine-somite stage). Primitive embryonic hearts microinjected with recombinant human (rh)VEGF165 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.
心血管发育需要血管内皮生长因子（VEGF）及其受体（VEGFRs）进行信号传导。为了研究VEGF/VEGFR受体信号传导如何影响早期心内膜细胞行为，对处于五到九体节期的鹌鹑胚胎心脏施加升高的VEGF165水平。与未处理胚胎的心脏相比，显微注射重组人（rh）VEGF165的原始胚胎心脏表现出几种明显的畸形：心内膜管畸形，有曲折的索条和褶皱，周围的心胶样间隙减小，受影响心脏的管腔明显缩小。此外，胚胎心脏无法正常弯曲。弯曲抑制伴随着背侧心内膜明显未能萎缩——这一事件被认为是心脏弯曲所必需的。VEGF处理的心内膜不是萎缩，而是驻留内皮细胞数量显著增加。总体而言，数据表明VEGF处理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。我们得出结论，过量的VEGF信号传导最终导致一种物理或生物力学机制，该机制在广泛的组织水平长度尺度上起作用，导致严重的发育缺陷——心脏弯曲失败。
