Centro de Investigaciones Cardiovasculares, CCT-La Plata-CONICET, Facultad de Cs. Medicas, UNLP, La Plata, Argentina.
Department of Medicine, Center for Translational Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, 19107, USA.
J Physiol. 2021 Jul;599(14):3477-3493. doi: 10.1113/JP279376. Epub 2021 May 18.
Metabolic diseases (MetDs) embrace a series of pathologies characterized by abnormal body glucose usage. The known diseases included in this group are metabolic syndrome, prediabetes and diabetes mellitus types 1 and 2. All of them are chronic pathologies that present metabolic disturbances and are classified as multi-organ diseases. Cardiomyopathy has been extensively described in diabetic patients without overt macrovascular complications. The heart is severely damaged during the progression of the disease; in fact, diabetic cardiomyopathies are the main cause of death in MetDs. Insulin resistance, hyperglycaemia and increased free fatty acid metabolism promote cardiac damage through mitochondria. These organelles supply most of the energy that the heart needs to beat and to control essential cellular functions, including Ca signalling modulation, reactive oxygen species production and apoptotic cell death regulation. Several aspects of common mitochondrial functions have been described as being altered in diabetic cardiomyopathies, including impaired energy metabolism, compromised mitochondrial dynamics, deficiencies in Ca handling, increases in reactive oxygen species production, and a higher probability of mitochondrial permeability transition pore opening. Therefore, the mitochondrial role in MetD-mediated heart dysfunction has been studied extensively to identify potential therapeutic targets for improving cardiac performance. Herein we review the cardiac pathology in metabolic syndrome, prediabetes and diabetes mellitus, focusing on the role of mitochondrial dysfunctions.
代谢性疾病（Metabolic Diseases，MetDs）涵盖了一系列以异常血糖利用为特征的病理状态。该类疾病包括代谢综合征、糖尿病前期、1 型和 2 型糖尿病。这些疾病均为慢性疾病，表现出代谢紊乱，并被归类为多器官疾病。糖尿病患者中广泛描述了心肌病，而这些患者没有明显的大血管并发症。在疾病进展过程中心脏严重受损；事实上，糖尿病性心肌病是 MetDs 中主要的死亡原因。胰岛素抵抗、高血糖和增加的游离脂肪酸代谢通过线粒体促进心脏损伤。这些细胞器提供了心脏跳动和控制基本细胞功能所需的大部分能量，包括 Ca 信号调节、活性氧物质产生和细胞凋亡的调节。在糖尿病性心肌病中，已经描述了一些常见的线粒体功能异常，包括能量代谢受损、线粒体动力学受损、Ca 处理缺陷、活性氧物质产生增加以及线粒体通透性转换孔（mitochondrial permeability transition pore，mPTP）开放的可能性增加。因此，广泛研究了线粒体在 MetD 介导的心脏功能障碍中的作用，以确定改善心脏功能的潜在治疗靶点。本文综述了代谢综合征、糖尿病前期和糖尿病中的心脏病理学，重点关注线粒体功能障碍的作用。
