Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, Singapore, Singapore.
Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Curr Hypertens Rep. 2020 Feb 29;22(3):22. doi: 10.1007/s11906-020-1028-6.
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.
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.
肾素-血管紧张素-醛固酮系统（RAAS）在调节血压和体液方面发挥着重要作用，这有助于高血压和心血管/肾脏疾病的病理生理学。然而，越来越多的证据进一步揭示了这个信号转导系统的复杂性，包括与其他受体和蛋白的直接相互作用。这篇综述重点介绍了 RAAS 的最新研究进展，重点是其受体。
全身和局部产生的血管紧张素 II（Ang II）与血管紧张素 II 型 1 受体（AT1R）结合，并发挥强大的生物学功能。最近的研究表明，Ang II 诱导的血管紧张素 II 型 2 受体（AT2R）激活产生与 AT1R 相反的作用。然而，越来越多的证据现在扩展了 RAAS 的组成部分，包括（前）肾素受体、血管紧张素转换酶 2、血管紧张素 1-7 和 Mas 受体。此外，AT1R 和 AT2R 的信号转导不仅受 Ang II 调节，还受其受体相关蛋白如 AT1R 相关蛋白和 AT2R 相互作用蛋白的调节。最近的研究表明，局部醛固酮受体的不适当激活通过醛固酮依赖性和非依赖性机制导致心血管和肾脏组织损伤。由于 RAAS 信号转导的机制仍有待阐明，因此需要进一步研究以探索 RAAS 的新分子机制，这将提供除现有 RAAS 阻滞剂之外的替代治疗药物。
