The Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou 350004, China; Fujian University of Traditional Chinese Medicine, Fuzhou 350000, China.
Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Cell Signal. 2024 Dec;124:111426. doi: 10.1016/j.cellsig.2024.111426. Epub 2024 Sep 19.
The intricate physiological and pathological diversity of the Renin-Angiotensin-Aldosterone System (RAAS) underpins its role in maintaining bodily equilibrium. This paper delves into the classical axis (Renin-ACE-Ang II-AT1R axis), the protective arm (ACE2-Ang (1-7)-MasR axis), the prorenin-PRR-MAP kinases ERK1/2 axis, and the Ang IV-AT4R-IRAP cascade of RAAS, examining their functions in both physiological and pathological states. The dysregulation or hyperactivation of RAAS is intricately linked to numerous diseases, including cardiovascular disease (CVD), renal damage, metabolic disease, eye disease, Gastrointestinal disease, nervous system and reproductive system diseases. This paper explores the pathological mechanisms of RAAS in detail, highlighting its significant role in disease progression. Currently, in addition to traditional drugs like ACEI, ARB, and MRA, several novel therapeutics have emerged, such as angiotensin receptor-enkephalinase inhibitors, nonsteroidal mineralocorticoid receptor antagonists, aldosterone synthase inhibitors, aminopeptidase A inhibitors, and angiotensinogen inhibitors. These have shown potential efficacy and application prospects in various clinical trials for related diseases. Through an in-depth analysis of RAAS, this paper aims to provide crucial insights into its complex physiological and pathological mechanisms and offer valuable guidance for developing new therapeutic approaches. This comprehensive discussion is expected to advance the RAAS research field and provide innovative ideas and directions for future clinical treatment strategies.
肾素-血管紧张素-醛固酮系统（RAAS）的复杂生理和病理多样性是其维持身体平衡的基础。本文深入探讨了 RAAS 的经典轴（肾素-血管紧张素转换酶-血管紧张素 II-AT1R 轴）、保护轴（血管紧张素转换酶 2-血管紧张素（1-7）-MasR 轴）、原肾素-PRR-MAP 激酶 ERK1/2 轴和 RAAS 的血管紧张素 IV-AT4R-IRAP 级联，研究它们在生理和病理状态下的功能。RAAS 的失调或过度激活与许多疾病密切相关，包括心血管疾病（CVD）、肾脏损伤、代谢疾病、眼部疾病、胃肠道疾病、神经系统疾病和生殖系统疾病。本文详细探讨了 RAAS 的病理机制，强调了它在疾病进展中的重要作用。目前，除了 ACEI、ARB 和 MRA 等传统药物外，还出现了几种新型治疗药物，如血管紧张素受体-脑啡肽酶抑制剂、非甾体类盐皮质激素受体拮抗剂、醛固酮合酶抑制剂、氨肽酶 A 抑制剂和血管紧张素原抑制剂。这些药物在各种相关疾病的临床试验中显示出了潜在的疗效和应用前景。通过对 RAAS 的深入分析，本文旨在为其复杂的生理和病理机制提供重要的见解，并为开发新的治疗方法提供有价值的指导。这一全面的讨论有望推动 RAAS 研究领域的发展，并为未来的临床治疗策略提供创新的思路和方向。
