Kengo Azushima1,2, Norihiko Morisawa3, Kouichi Tamura2, Akira Nishiyama4. 1. Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, Singapore, Singapore. 2. Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan. 3. Department of Pharmacology, Faculty of Medicine, Kagawa University, Takamatsu, Kagawa, Japan. 4. Department of Pharmacology, Faculty of Medicine, Kagawa University, Takamatsu, Kagawa, Japan. akira@med.kagawa-u.ac.jp.
Abstract
PURPOSE OF REVIEW: The renin-angiotensin-aldosterone system (RAAS) plays important roles in regulating blood pressure and body fluid, which contributes to the pathophysiology of hypertension and cardiovascular/renal diseases. However, accumulating evidence has further revealed the complexity of this signal transduction system, including direct interactions with other receptors and proteins. This review focuses on recent research advances in RAAS with an emphasis on its receptors. RECENT FINDINGS: Both systemically and locally produced angiotensin II (Ang II) bind to Ang II type 1 receptor (AT1R) and elicit strong biological functions. Recent studies have shown that Ang II-induced activation of Ang II type 2 receptor (AT2R) elicits the opposite functions to those of AT1R. However, accumulating evidence has now expanded the components of RAAS, including (pro)renin receptor, angiotensin-converting enzyme 2, angiotensin 1-7, and Mas receptor. In addition, the signal transductions of AT1R and AT2R are regulated by not only Ang II but also its receptor-associated proteins such as AT1R-associated protein and AT2R-interacting protein. Recent studies have indicated that inappropriate activation of local mineralocorticoid receptor contributes to cardiovascular and renal tissue injuries through aldosterone-dependent and -independent mechanisms. Since the mechanisms of RAAS signal transduction still remain to be elucidated, further investigations are necessary to explore novel molecular mechanisms of the RAAS, which will provide alternative therapeutic agents other than existing RAAS blockers.
PURPOSE OF REVIEW: The renin-angiotensin-aldosterone system (RAAS) plays important roles in regulating blood pressure and body fluid, which contributes to the pathophysiology of hypertension and cardiovascular/renal diseases. However, accumulating evidence has further revealed the complexity of this signal transduction system, including direct interactions with other receptors and proteins. This review focuses on recent research advances in RAAS with an emphasis on its receptors. RECENT FINDINGS: Both systemically and locally produced angiotensin II (Ang II) bind to Ang II type 1 receptor (AT1R) and elicit strong biological functions. Recent studies have shown that Ang II-induced activation of Ang II type 2 receptor (AT2R) elicits the opposite functions to those of AT1R. However, accumulating evidence has now expanded the components of RAAS, including (pro)renin receptor, angiotensin-converting enzyme 2, angiotensin 1-7, and Mas receptor. In addition, the signal transductions of AT1R and AT2R are regulated by not only Ang II but also its receptor-associated proteins such as AT1R-associated protein and AT2R-interacting protein. Recent studies have indicated that inappropriate activation of local mineralocorticoid receptor contributes to cardiovascular and renal tissue injuries through aldosterone-dependent and -independent mechanisms. Since the mechanisms of RAAS signal transduction still remain to be elucidated, further investigations are necessary to explore novel molecular mechanisms of the RAAS, which will provide alternative therapeutic agents other than existing RAAS blockers.
Entities:
Keywords:
(Pro)renin receptor (PRR); Angiotensin type 1 receptor (AT1R); Angiotensin type 2 receptor (AT2R); Mas receptor (MasR); Mineralocorticoid receptor (MR)
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