Lack of pericytes leads to endothelial hyperplasia and abnormal vascular morphogenesis.
Lack of pericytes leads to endothelial hyperplasia and abnormal vascular morphogenesis.
复制标题
缺乏周细胞会导致内皮增生和异常血管形态发生。
DOI：
10.1083/jcb.153.3.543
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发表时间：
2001-04-30
影响因子：
7.8
通讯作者：
Betsholtz, C
中科院分区：
文献类型：
--
作者：
Hellstrom, M;Gerhardt, H;Kalen, M;Li, X;Eriksson, U;Wolburg, H;Betsholtz, C
周细胞(PC)与新生血管的结合被认为调节内皮细胞(EC)的增殖、存活、迁移、分化和血管分支。在这里，我们使用PDGF-B和PDGF受体-β(PDGFFR-β)缺陷的小鼠作为在没有PC的情况下脑血管生成的活体模型来解决这些问题。定量形态分析表明，这些突变体具有正常的微血管密度、长度和分支点数量。然而，PC的缺失与内皮细胞增生、毛细血管直径增大、EC形态和超微结构异常、某些连接蛋白的细胞分布改变以及跨内皮通透性增加的形态学迹象有关。胚胎11.5天即可见脑内皮细胞增生，并持续至整个胚胎发育过程。从E13.5开始，血管内皮生长因子-A(VEGF-A)和其他对代谢应激反应的基因上调，表明异常的微血管结构具有全身性代谢后果。血管内皮生长因子-A的上调与胎盘血管异常和心脏扩张的发生在时间上相关。因此，尽管PC缺乏似乎对E13.5之前的EC数有直接影响，但随后增加的血管内皮生长因子-A水平可能进一步破坏微血管构筑，促进血管通透性，并有助于在妊娠晚期观察到的PDGFB和PDGFFR-β敲除胚胎形成水肿型表型。
The association of pericytes (PCs) to newly formed blood vessels has been suggested to regulate endothelial cell (EC) proliferation, survival, migration, differentiation, and vascular branching. Here, we addressed these issues using PDGF-B– and PDGF receptor-β (PDGFR-β)–deficient mice as in vivo models of brain angiogenesis in the absence of PCs. Quantitative morphological analysis showed that these mutants have normal microvessel density, length, and number of branch points. However, absence of PCs correlates with endothelial hyperplasia, increased capillary diameter, abnormal EC shape and ultrastructure, changed cellular distribution of certain junctional proteins, and morphological signs of increased transendothelial permeability. Brain endothelial hyperplasia was observed already at embryonic day (E) 11.5 and persisted throughout development. From E 13.5, vascular endothelial growth factor-A (VEGF-A) and other genes responsive to metabolic stress became upregulated, suggesting that the abnormal microvessel architecture has systemic metabolic consequences. VEGF-A upregulation correlated temporally with the occurrence of vascular abnormalities in the placenta and dilation of the heart. Thus, although PC deficiency appears to have direct effects on EC number before E 13.5, the subsequent increased VEGF-A levels may further abrogate microvessel architecture, promote vascular permeability, and contribute to formation of the edematous phenotype observed in late gestation PDGF-B and PDGFR-β knock out embryos.