Ivey Melanie E, Osman Narin, Little Peter J
Cell Biology of Diabetes Laboratory, Baker Heart Research Institute, Melbourne, Victoria, Australia.
Atherosclerosis. 2008 Aug;199(2):237-47. doi: 10.1016/j.atherosclerosis.2008.03.006. Epub 2008 Mar 16.
Atherosclerosis is the primary ischaemic vascular condition underlying a majority of cardiovascular disease related deaths. Endothelin-1 is a vasoactive peptide agent upregulated in atherosclerosis and in conjunction with its G protein-coupled receptors exerts diverse actions on all cells of the vasculature in particular vascular smooth muscle cells (VSMC). The effects of endothelin-1 include cell proliferation, migration and contraction, and the induction of extracellular matrix components and growth factors. VSMC as the major component of the neointima in atherosclerotic plaques accordingly play a key role in atherogenesis. In this review we examine classic and novel signalling pathways activated by endothelin-1 in VSMC (including phospholipase C, adenylate cyclase, Rho kinase, transactivation of receptor tyrosine kinases, mitogen activated protein kinase cascades and beta-arrestin) and their likely impact on the development and progression of atherosclerosis.
动脉粥样硬化是大多数心血管疾病相关死亡的主要缺血性血管疾病。内皮素-1是一种血管活性肽物质，在动脉粥样硬化中上调，并与其G蛋白偶联受体一起对脉管系统的所有细胞，特别是血管平滑肌细胞（VSMC）发挥多种作用。内皮素-1的作用包括细胞增殖、迁移和收缩，以及诱导细胞外基质成分和生长因子。VSMC作为动脉粥样硬化斑块中新内膜的主要成分，因此在动脉粥样硬化形成中起关键作用。在本综述中，我们研究了内皮素-1在VSMC中激活的经典和新型信号通路（包括磷脂酶C、腺苷酸环化酶、Rho激酶、受体酪氨酸激酶的反式激活、丝裂原活化蛋白激酶级联反应和β-抑制蛋白）及其对动脉粥样硬化发展和进展的可能影响。
