Batista João Pedro Thimotheo, Faria André Oliveira Vilela de, Ribeiro Thomas Felipe Silva, Simões E Silva Ana Cristina
Laboratório Interdisciplinar de Investigação Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 30130-100, MG, Brazil.
Departamento de Pediatria, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 30130-100, MG, Brazil.
Life (Basel). 2023 Jul 21;13(7):1598. doi: 10.3390/life13071598.
Diabetic cardiomyopathy refers to myocardial dysfunction in type 2 diabetes, but without the traditional cardiovascular risk factors or overt clinical atherosclerosis and valvular disease. The activation of the renin-angiotensin system (RAS), oxidative stress, lipotoxicity, maladaptive immune responses, imbalanced mitochondrial dynamics, impaired myocyte autophagy, increased myocyte apoptosis, and fibrosis contribute to diabetic cardiomyopathy. This review summarizes the studies that address the link between cardiomyopathy and the RAS in humans and presents proposed pathophysiological mechanisms underlying this association. The RAS plays an important role in the development and progression of diabetic cardiomyopathy. The over-activation of the classical RAS axis in diabetes leads to the increased production of angiotensin (Ang) II, angiotensin type 1 receptor activation, and aldosterone release, contributing to increased oxidative stress, fibrosis, and cardiac remodeling. In contrast, Ang-(1-7) suppresses oxidative stress, inhibits tissue fibrosis, and prevents extensive cardiac remodeling. Angiotensin-converting-enzyme (ACE) inhibitors and angiotensin receptor blockers improve heart functioning and reduce the occurrence of diabetic cardiomyopathy. Experimental studies also show beneficial effects for Ang-(1-7) and angiotensin-converting enzyme 2 infusion in improving heart functioning and tissue injury. Further research is necessary to fully understand the pathophysiology of diabetic cardiomyopathy and to translate experimental findings into clinical practice.
糖尿病性心肌病是指2型糖尿病患者出现的心肌功能障碍，但不存在传统的心血管危险因素或明显的临床动脉粥样硬化及瓣膜疾病。肾素-血管紧张素系统（RAS）的激活、氧化应激、脂毒性、适应性免疫反应失调、线粒体动力学失衡、心肌细胞自噬受损、心肌细胞凋亡增加以及纤维化均与糖尿病性心肌病的发生有关。本综述总结了关于人类心肌病与RAS之间联系的研究，并提出了这种关联潜在的病理生理机制。RAS在糖尿病性心肌病的发生和发展中起重要作用。糖尿病中经典RAS轴的过度激活导致血管紧张素（Ang）II生成增加、血管紧张素1型受体激活以及醛固酮释放，从而导致氧化应激增加、纤维化和心脏重塑。相比之下，Ang-(1-7)可抑制氧化应激、抑制组织纤维化并防止广泛的心脏重塑。血管紧张素转换酶（ACE）抑制剂和血管紧张素受体阻滞剂可改善心脏功能并减少糖尿病性心肌病的发生。实验研究还表明，输注Ang-(1-7)和血管紧张素转换酶2对改善心脏功能和组织损伤具有有益作用。有必要进行进一步研究以充分了解糖尿病性心肌病的病理生理学，并将实验结果转化为临床实践。
