CRIM1 is necessary for coronary vascular endothelial cell development and homeostasis
CRIM1 is necessary for coronary vascular endothelial cell development and homeostasis
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DOI：
10.1007/s10735-016-9702-3
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发表时间：
2017-02-01
影响因子：
3.2
通讯作者：
Piper, Michael
中科院分区：
文献类型：
--
作者：
Iyer, Swati;Chhabra, Yash;Piper, Michael
内皮细胞是冠状动脉血管的重要组成部分，但调节其发育的因素仍不明确。在这里，我们揭示了跨膜蛋白cri1在介导心脏内皮细胞发育中的新作用。在体内缺乏Crim1的情况下，冠状动脉血管畸形，内皮细胞数量减少，典型的BMP通路失调。此外，我们发现CRIM1可以结合IGF，并调节内皮细胞内的IGF信号传导。最后，人心脏内皮细胞中crip1的缺失导致内皮基因的错误调控，通过通路分析预测，这与炎症反应和细胞溶解的增加有关，使人联想到心血管疾病发病机制中的内皮细胞功能障碍。总的来说，这些发现暗示了cri1在冠状血管内皮细胞发育和稳态中的作用。
Endothelial cells form a critical component of the coronary vasculature, yet the factors regulating their development remain poorly defined. Here we reveal a novel role for the transmembrane protein CRIM1 in mediating cardiac endothelial cell development. In the absence of Crim1 in vivo, the coronary vasculature is malformed, the number of endothelial cells reduced, and the canonical BMP pathway dysregulated. Moreover, we reveal that CRIM1 can bind IGFs, and regulate IGF signalling within endothelial cells. Finally, loss of CRIM1 from human cardiac endothelial cells results in misregulation of endothelial genes, predicted by pathway analysis to be involved in an increased inflammatory response and cytolysis, reminiscent of endothelial cell dysfunction in cardiovascular disease pathogenesis. Collectively, these findings implicate CRIM1 in endothelial cell development and homeostasis in the coronary vasculature.