Biomedical Research Center, Qatar University, Al-Tarfa, 2371, Doha, Qatar.
Department of Bioscience Research, University of Tennessee Health Science Center, Memphis, TN, USA.
Pflugers Arch. 2022 Jan;474(1):63-81. doi: 10.1007/s00424-021-02651-x. Epub 2021 Dec 30.
Experimental and clinical evidence suggests that diabetic subjects are predisposed to a distinct cardiovascular dysfunction, known as diabetic cardiomyopathy (DCM), which could be an autonomous disease independent of concomitant micro and macrovascular disorders. DCM is one of the prominent causes of global morbidity and mortality and is on a rising trend with the increase in the prevalence of diabetes mellitus (DM). DCM is characterized by an early left ventricle diastolic dysfunction associated with the slow progression of cardiomyocyte hypertrophy leading to heart failure, which still has no effective therapy. Although the well-known "Renin Angiotensin Aldosterone System (RAAS)" inhibition is considered a gold-standard treatment in heart failure, its role in DCM is still unclear. At the cellular level of DCM, RAAS induces various secondary mechanisms, adding complications to poor prognosis and treatment of DCM. This review highlights the importance of RAAS signaling and its major secondary mechanisms involving inflammation, oxidative stress, mitochondrial dysfunction, and autophagy, their role in establishing DCM. In addition, studies lacking in the specific area of DCM are also highlighted. Therefore, understanding the complex role of RAAS in DCM may lead to the identification of better prognosis and therapeutic strategies in treating DCM.
实验和临床证据表明，糖尿病患者易患一种独特的心血管功能障碍，称为糖尿病心肌病（DCM），这可能是一种独立于伴发的微血管和大血管疾病的自主疾病。DCM 是全球发病率和死亡率的主要原因之一，随着糖尿病（DM）患病率的增加，呈上升趋势。DCM 的特征是早期左心室舒张功能障碍，伴有心肌细胞肥大的缓慢进展，导致心力衰竭，目前仍没有有效的治疗方法。尽管众所周知的“肾素-血管紧张素-醛固酮系统（RAAS）”抑制被认为是心力衰竭的金标准治疗方法，但它在 DCM 中的作用仍不清楚。在 DCM 的细胞水平上，RAAS 诱导各种继发性机制，增加了 DCM 预后不良和治疗的并发症。本综述强调了 RAAS 信号及其主要继发性机制（涉及炎症、氧化应激、线粒体功能障碍和自噬）在建立 DCM 中的重要性。此外，还强调了在 DCM 特定领域缺乏研究的情况。因此，了解 RAAS 在 DCM 中的复杂作用可能有助于确定更好的预后和治疗策略来治疗 DCM。
