Molecular mechanisms of angiotensin II-induced vascular injury.
Blockers of the renin-angiotensin system are used in the treatment of several cardiovascular and renal diseases, including hypertension, atherosclerosis, and cardiac failure. Angiotensin II plays an essential role in the pathogenesis of these diseases through the regulation of cell growth, inflammation, and fibrosis. There are two main angiotensin II receptors, AT(1) and AT(2). The AT(1) receptor is responsible for most of the pathophysiologic actions of angiotensin II, including cell proliferation, production of growth factors and cytokines, and fibrosis. AT(2) causes antiproliferation and counteracts the cell growth induced by AT(1) activation. We review the mechanisms whereby AT(1) and AT(2) receptors elicit their respective actions. We discuss the current understanding of the signaling mechanisms involved in angiotensin II-induced vascular damage, describing the mediators (growth factors and cytokines) and intracellular signals (activation of protein kinases, transcription factors, and redox pathways) implicated in these processes, with special emphasis on novel information and open questions.
Ruiz-Ortega
Marta
M
Vascular and Renal Research Laboratory, Fundación Jiménez Díaz, Avda. Reyes Católicos, 2, 28040 Madrid, Spain. mruizo@fjd.es
Ruperez
Monica
M
Esteban
Vanesa
V
Egido
Jesús
J
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001158:Arteries / Q000473:pathology* / Q000502:physiology / Q000503:physiopathology; D002455:Cell Division / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism; D005355:Fibrosis; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology; D015398:Signal Transduction
D006133:Growth Substances; D018836:Inflammation Mediators; D016328:NF-kappa B; D000804:Angiotensin II; D020929:Mitogen-Activated Protein Kinase Kinases