Conundrum of pathogenesis of diabetic cardiomyopathy: role of vascular endothelial dysfunction, reactive oxygen species, and mitochondria
Conundrum of pathogenesis of diabetic cardiomyopathy: role of vascular endothelial dysfunction, reactive oxygen species, and mitochondria
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DOI：
10.1007/s11010-013-1861-x
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发表时间：
2014-01-01
影响因子：
4.3
通讯作者：
Maulik, Nilanjana
中科院分区：
文献类型：
--
作者：
Joshi, Mandip;Kotha, Sainath R.;Maulik, Nilanjana
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不全，其与糖尿病患者的冠状动脉疾病和高血压无关。糖尿病心肌病的发病机制涉及一系列复杂的因素，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。然而，糖尿病心肌病发病机制的确切机制尚未建立。糖尿病心肌病的发病机制涉及血管内皮功能障碍、微血管病变、活性氧、氧化应激、线粒体功能障碍等多种因素。虽然很难确定每个因素如何导致疾病，但ROS和线粒体功能障碍的参与正在成为糖尿病心肌病发病机制的领跑者。本文综述了血管内皮功能障碍、活性氧、氧化应激和血管病变在糖尿病心肌病发病机制中的作用。此外，该综述强调，必须解决这个难题，以牢固地建立线粒体和/或ROS机制（S），通过确定它们在空间和时间水平上参与糖尿病心肌病的最关键的分子参与者，作为特异性和有效的药理学/治疗干预的目标。
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.