Endothelin-1-induced signaling pathways in vascular smooth muscle cells
Endothelin-1-induced signaling pathways in vascular smooth muscle cells
复制标题
DOI：
10.2174/157016107779317161
复制
发表时间：
2007-01-01
影响因子：
4.5
通讯作者：
Srivastava, Ashok K.
中科院分区：
文献类型：
--
作者：
Bouallegue, Ali;Daou, Grace Bou;Srivastava, Ashok K.
内皮素-1（ET-1）是一种血管活性肽，被认为参与了高血压、动脉粥样硬化、肥大和再狭窄等血管异常的发病机制。ET-1通过激活两种受体亚型ET-A和ET-B发挥其生物学效应，ET-A和ET-B属于跨膜鸟嘌呤核苷酸结合蛋白偶联受体（GPCR）大家族。ET-1受体激活导致几种信号传导途径的刺激，包括促分裂原活化蛋白激酶（MAPK）、磷脂酰肌醇3-激酶（PI 3-K）和蛋白激酶B（PK B）。Ca ~（2+）/钙调素依赖性蛋白激酶（CaMK）、蛋白激酶C（PKC）以及受体和非受体蛋白酪氨酸激酶在ET-1激活MAPK和PI 3-K/PKB信号通路中起中介作用。ET-1对这些信号通路的激活与细胞肥大、生长、增殖和细胞存活的调节密切相关，本文综述了这些信号通路在血管平滑肌细胞（VSMCs）中的作用，并着重讨论了它们在血管病理生理学中的潜在作用。
Endothelin-1 (ET-1), a vasoactive peptide, is believed to contribute to the pathogenesis of vascular abnormalities such as hypertension, atherosclerosis, hypertrophy and restenosis. ET-1 elicits its biological effects through the activation of two receptor subtypes, ET-A and ET-B that belong to a large family of transmembrane guanine nucleotide-binding protein-coupled receptors (GPCRs). ET-1 receptor activation results in the stimulation of several signaling pathways including mitogen-activated protein kinases (MAPKs), phosphatidylinositol 3-kinase (PI3-K) and protein kinase B (PKB). An intermediary role of Ca2+/calmodulin-dependent protein kinases (CaMK), protein kinase C (PKC) as well as receptor and non-receptor protein tyrosine kinases in triggering the activation of MAPK and PI3-K/PKB signaling in response to ET-1 has been suggested. Activation of these pathways by ET-1 is intimately linked with the regulation of cellular hypertrophy, growth, proliferation and cell survival.Here we provide an overview of these signaling pathways in vascular smooth muscle cells (VSMCs) with an emphasis on their potential role in vascular pathophysiology.