Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system.
The renin-angiotensin system is a central component of the physiological and pathological responses of cardiovascular system. Its primary effector hormone, angiotensin II (ANG II), not only mediates immediate physiological effects of vasoconstriction and blood pressure regulation, but is also implicated in inflammation, endothelial dysfunction, atherosclerosis, hypertension, and congestive heart failure. The myriad effects of ANG II depend on time (acute vs. chronic) and on the cells/tissues upon which it acts. In addition to inducing G protein- and non-G protein-related signaling pathways, ANG II, via AT(1) receptors, carries out its functions via MAP kinases (ERK 1/2, JNK, p38MAPK), receptor tyrosine kinases [PDGF, EGFR, insulin receptor], and nonreceptor tyrosine kinases [Src, JAK/STAT, focal adhesion kinase (FAK)]. AT(1)R-mediated NAD(P)H oxidase activation leads to generation of reactive oxygen species, widely implicated in vascular inflammation and fibrosis. ANG II also promotes the association of scaffolding proteins, such as paxillin, talin, and p130Cas, leading to focal adhesion and extracellular matrix formation. These signaling cascades lead to contraction, smooth muscle cell growth, hypertrophy, and cell migration, events that contribute to normal vascular function, and to disease progression. This review focuses on the structure and function of AT(1) receptors and the major signaling mechanisms by which angiotensin influences cardiovascular physiology and pathology.
Mehta
Puja K
PK
Division of Cardiology, 319 WMB, Emory University, 1639 Pierce Drive, Atlanta, GA 30322, USA.
Griendling
Kathy K
KK
D000804:Angiotensin II / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology / Q000503:physiopathology*; D002320:Cardiovascular Physiological Phenomena; D006801:Humans; D044140:Receptor, Angiotensin, Type 1 / Q000737:chemistry / Q000502:physiology; D044139:Receptor, Angiotensin, Type 2 / Q000502:physiology; D012084:Renin-Angiotensin System / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013329:Structure-Activity Relationship; D014652:Vascular Diseases / Q000503:physiopathology
D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II