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, AT1 and AT2. The AT1 receptor is responsible for most of the pathophysiologic actions of angiotensin II, including cell proliferation, production of growth factors and cytokines, and fibrosis. AT2 causes antiproliferation and counteracts the cell growth induced by AT1 activation. We review the mechanisms whereby AT1 and AT2 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.