Affiliation:
1. Cardiovascular Research Center, Department of Physiology, Temple University School of Medicine, Philadelphia, PA 19140, U.S.A.
2. Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, U.S.A.
Abstract
The intracellular signal transduction of AngII (angiotensin II) has been implicated in cardiovascular diseases, such as hypertension, atherosclerosis and restenosis after injury. AT1 receptor (AngII type-1 receptor), a G-protein-coupled receptor, mediates most of the physiological and pathophysiological actions of AngII, and this receptor is predominantly expressed in cardiovascular cells, such as VSMCs (vascular smooth muscle cells). AngII activates various signalling molecules, including G-protein-derived second messengers, protein kinases and small G-proteins (Ras, Rho, Rac etc), through the AT1 receptor leading to vascular remodelling. Growth factor receptors, such as EGFR (epidermal growth factor receptor), have been demonstrated to be ‘trans’-activated by the AT1 receptor in VSMCs to mediate growth and migration. Rho and its effector Rho-kinase/ROCK are also implicated in the pathological cellular actions of AngII in VSMCs. Less is known about the endothelial AngII signalling; however, recent studies suggest the endothelial AngII signalling positively, as well as negatively, regulates the NO (nitric oxide) signalling pathway and, thereby, modulates endothelial dysfunction. Moreover, selective AT1-receptor-interacting proteins have recently been identified that potentially regulate AngII signal transduction and their pathogenic functions in the target organs. In this review, we focus our discussion on the recent findings and concepts that suggest the existence of the above-mentioned novel signalling mechanisms whereby AngII mediates the formation of cardiovascular diseases.
Reference123 articles.
1. Signal transduction mechanisms mediating the physiological and pathophysiological actions of angiotensin II in vascular smooth muscle cells;Touyz;Pharmacol. Rev.,2000
2. Angiotensin II cell signalling: physiological and pathological effects in the cardiovascular system;Mehta;Am. J. Physiol. Cell Physiol.,2007
3. Angiotensin II signaling in vascular smooth muscle;Griendling;New concepts. Hypertension,1997
4. Metalloprotease-dependent ErbB ligand shedding in mediating EGFR transactivation and vascular remodelling;Eguchi;Biochem. Soc. Trans.,2003
5. Angiotensin II signaling pathways mediated by tyrosine kinases;Yin;Int. J. Biochem. Cell Biol.,2003
Cited by
349 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献