Molecular and cellular basis of the aetiology and management of diabetic cardiomyopathy: A short review
Molecular and cellular basis of the aetiology and management of diabetic cardiomyopathy: A short review
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DOI：
10.1023/b:mcbi.0000028755.86521.11
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发表时间：
2004-06-01
影响因子：
4.3
通讯作者：
Adeghate, E
中科院分区：
文献类型：
--
作者：
Adeghate, E
糖尿病是影响全世界数百万人的最常见的慢性疾病之一。包括心肌梗死在内的心血管并发症是糖尿病患者死亡的主要原因之一。糖尿病可引起心脏异常病理改变，包括细胞肥大、神经病变、间质纤维化、肌细胞溶解和凋亡以及脂质沉积。此外，在I型和II型糖尿病中，心肌细胞的胞质细胞器包括质膜、胞浆和肌浆网也受损。高血糖症是糖尿病患者发生糖尿病性心肌病的主要病因。高脂血症促进活性氧（ROS）和氮类（RNS）的产生。ROS和RNS的释放诱导氧化应激，导致基因表达异常、信号转导错误和心肌细胞凋亡。高胆固醇血症还通过p53和细胞色素c激活的caspase-3途径的激活诱导细胞凋亡。结缔组织生长因子的刺激和细胞外基质蛋白中晚期糖基化终产物的形成诱导胶原交联，并促成在糖尿病受试者的心脏内膜中观察到的纤维化。在信号转导方面，由于调节细胞内Ca 2+的蛋白质的表达和功能的改变，细胞内Ca 2+信号传导的缺陷也发生在糖尿病中。所有这些异常都会导致心脏的严重功能障碍。β-肾上腺素受体拮抗剂、ACE抑制剂、内皮素受体拮抗剂（Bonestan）、肾上腺髓质素、激素（胰岛素、IGF-1）和抗氧化剂（放大蛋白、金属硫蛋白、维生素C和E）可减少糖尿病性心肌病的间质纤维化并改善心脏功能。
Diabetes mellitus is one of the most common chronic diseases affecting millions of people worldwide. Cardiovascular complication including myocardial infarction is one of the major causes of death in diabetic patients. Diabetes mellitus induces abnormal pathological findings including cell hypertrophy, neuropathy, interstitial fibrosis, myocytolysis and apoptosis and lipid deposits in the heart. In addition, the cytoplasmic organelles of cardiomyocytes including the plasma membrane, mitochondrion and sarcoplasmic reticulum are also impaired in both type I and type II diabetes. Hyperglycaemia is a major aetiological factor in the development of diabetic cardiomyopathy in patients suffering from diabetes. Hyperglycaemia promotes the production of reactive oxygen (ROS) and nitrogen species (RNS). The release of ROS and RNS induces oxidative stress leading to abnormal gene expression, faulty signal transduction and apoptosis of cardiomyocytes. Hyperglycaemia also induces apoptosis by p53 and the activation of the cytochrome c-activated caspase-3 pathway. Stimulation of connective tissue growth factor and the formation of advanced glycation end products in extracellular matrix proteins induces collagen cross-linking and contribute to the fibrosis observed in the interstitium of the heart of diabetic subjects. In terms of signal transduction, defects in intracellular Ca2+ signalling due to alteration of expression and function of proteins that regulate intracellular Ca2+ also occur in diabetes. All of these abnormalities result in gross dysfunction of the heart. Beta-adrenoreceptor antagonists, ACE inhibitors, endothelin-receptor antagonist (Bonestan), adrenomedullin, hormones ( insulin, IGF-1) and antioxidants (magniferin, metallothionein, vitamins C and E) reduce interstitial fibrosis and improve cardiac function in diabetic cardiomyopathy.