Department of Surgery, University of Connecticut Health Center, Farmington Avenue, Farmington, CT, 06032, USA.
Mol Cell Biochem. 2014 Jan;386(1-2):233-49. doi: 10.1007/s11010-013-1861-x. Epub 2013 Dec 4.
Diabetic cardiomyopathy and heart failure have been recognized as the leading causes of mortality among diabetics. Diabetic cardiomyopathy has been characterized primarily by the manifestation of left ventricular dysfunction that is independent of coronary artery disease and hypertension among the patients affected by diabetes mellitus. A complex array of contributing factors including the hypertrophy of left ventricle, alterations of metabolism, microvascular pathology, insulin resistance, fibrosis, apoptotic cell death, and oxidative stress have been implicated in the pathogenesis of diabetic cardiomyopathy. Nevertheless, the exact mechanisms underlying the pathogenesis of diabetic cardiomyopathy are yet to be established. The critical involvement of multifarious factors including the vascular endothelial dysfunction, microangiopathy, reactive oxygen species (ROS), oxidative stress, mitochondrial dysfunction has been identified in the mechanism of pathogenesis of diabetic cardiomyopathy. Although it is difficult to establish how each factor contributes to disease, the involvement of ROS and mitochondrial dysfunction are emerging as front-runners in the mechanism of pathogenesis of diabetic cardiomyopathy. This review highlights the role of vascular endothelial dysfunction, ROS, oxidative stress, and mitochondriopathy in the pathogenesis of diabetic cardiomyopathy. Furthermore, the review emphasizes that the puzzle has to be solved to firmly establish the mitochondrial and/or ROS mechanism(s) by identifying their most critical molecular players involved at both spatial and temporal levels in diabetic cardiomyopathy as targets for specific and effective pharmacological/therapeutic interventions.
糖尿病性心肌病和心力衰竭已被认为是糖尿病患者死亡的主要原因。糖尿病性心肌病的主要特征是左心室功能障碍，这与糖尿病患者的冠状动脉疾病和高血压无关。一系列复杂的致病因素，包括左心室肥大、代谢改变、微血管病变、胰岛素抵抗、纤维化、细胞凋亡和氧化应激，都与糖尿病性心肌病的发病机制有关。然而，糖尿病性心肌病发病机制的确切机制尚未确定。血管内皮功能障碍、微血管病变、活性氧（ROS）、氧化应激、线粒体功能障碍等多种因素的关键参与，已被确定为糖尿病性心肌病发病机制中的重要因素。尽管很难确定每个因素对疾病的贡献程度，但 ROS 和线粒体功能障碍的参与正成为糖尿病性心肌病发病机制中的领跑者。本文综述了血管内皮功能障碍、ROS、氧化应激和线粒体病变在糖尿病性心肌病发病机制中的作用。此外，本文强调，必须通过确定糖尿病性心肌病中空间和时间水平上最关键的分子靶点，解决这个难题，以确定线粒体和/或 ROS 机制作为特定和有效的药物干预的靶点。
