Department of Biotechnology, Krishna University, Machilipatnam, Andhra Pradesh, India.
Heart Fail Rev. 2014 Jan;19(1):49-63. doi: 10.1007/s10741-013-9374-y.
Increasing evidence demonstrates that advanced glycation end products (AGEs) play a pivotal role in the development and progression of diabetic heart failure, although there are numerous other factors that mediate the disease response. AGEs are generated intra- and extracellularly as a result of chronic hyperglycemia. Then, following the interaction with receptors for advanced glycation end products (RAGEs), a series of events leading to vascular and myocardial damage are elicited and sustained, which include oxidative stress, increased inflammation, and enhanced extracellular matrix accumulation resulting in diastolic and systolic dysfunction. Whereas targeting glycemic control and treating additional risk factors, such as obesity, dyslipidemia, and hypertension, are mandatory to reduce chronic complications and prolong life expectancy in diabetic patients, drug therapy tailored to reducing the deleterious effects of the AGE-RAGE interactions is being actively investigated and showing signs of promise in treating diabetic cardiomyopathy and associated heart failure. This review shall discuss the formation of AGEs in diabetic heart tissue, potential targets of glycation in the myocardium, and underlying mechanisms that lead to diabetic cardiomyopathy and heart failure along with the use of AGE inhibitors and breakers in mitigating myocardial injury.
越来越多的证据表明，糖基化终产物（AGEs）在糖尿病心力衰竭的发生和发展中起着关键作用，尽管还有许多其他因素介导疾病反应。AGEs 是由于慢性高血糖而在细胞内和细胞外产生的。然后，在与晚期糖基化终产物受体（RAGEs）相互作用后，会引发一系列导致血管和心肌损伤的事件，并持续存在，包括氧化应激、炎症增加和细胞外基质积累，导致舒张和收缩功能障碍。虽然控制血糖和治疗其他危险因素（如肥胖、血脂异常和高血压）对于减少糖尿病患者的慢性并发症和延长预期寿命是强制性的，但针对减少 AGE-RAGE 相互作用的有害影响的药物治疗正在积极研究中，并在治疗糖尿病心肌病和相关心力衰竭方面显示出希望。这篇综述将讨论糖尿病心脏组织中 AGEs 的形成、心肌中糖基化的潜在靶点以及导致糖尿病心肌病和心力衰竭的潜在机制，以及 AGE 抑制剂和断裂剂在减轻心肌损伤中的应用。
