Patan S
Department of Radiation Oncology, Beth Israel Hospital, Boston, Massachusetts, 02114, USA.
Microvasc Res. 1998 Jul;56(1):1-21. doi: 10.1006/mvre.1998.2081.
As shown previously, TIE1 and TIE2 receptor tyrosine kinases are specifically expressed in endothelial cells during embryonic angiogenesis. A detailed analysis of the vascular malformations of homozygous mice for a targeting mutation of both receptors was performed at the histological and cellular level. The data demonstrate that the TIE1 and TIE2 receptor inversely and concomitantly mediate interactions between endothelial cells with their extracellular matrix and with surrounding mesenchymal cells. These interactions are obviously crucial for normal endothelial cell motility and/or attachment and also for recruitment of periendothelial cells. The analysis of the TIE2-deficient embryos demonstrates how these cell/cell- and cell/matrix interactions subsequently influence the formation of normally structured tissue folds that divide the vessel lumen. They are also essential for the formation of vessel loops that compose a new vascular network and for the development of the ventricle in the heart. Fold and loop formation follow the principles of intussusceptive microvascular growth. The localization of the cardiovascular malformations corresponds to the temporal and spatial expression pattern of the TIE2 receptor. Angiopoietin-1, a ligand that activates the TIE2 receptor, is expressed in mesenchymal cells surrounding the endothelium. This local relationship is indicative of a paracrine regulation.
如前所示，TIE1和TIE2受体酪氨酸激酶在胚胎血管生成过程中在内皮细胞中特异性表达。在组织学和细胞水平上对两种受体靶向突变的纯合小鼠的血管畸形进行了详细分析。数据表明，TIE1和TIE2受体反向并同时介导内皮细胞与其细胞外基质以及与周围间充质细胞之间的相互作用。这些相互作用显然对于正常内皮细胞的运动性和/或附着以及对周内皮细胞的募集至关重要。对TIE2缺陷胚胎的分析表明，这些细胞/细胞和细胞/基质相互作用随后如何影响分隔血管腔的正常结构组织褶皱的形成。它们对于构成新血管网络的血管环的形成以及心脏中心室的发育也必不可少。褶皱和环的形成遵循套入式微血管生长的原则。心血管畸形的定位与TIE2受体的时空表达模式相对应。血管生成素-1，一种激活TIE2受体的配体，在内皮周围的间充质细胞中表达。这种局部关系表明存在旁分泌调节。
