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抗晚期糖基化终产物(AGEs)的基础与临床研究:应对心血管疾病和糖尿病并发症的新化合物

Basic and Clinical Research Against Advanced Glycation End Products (AGEs): New Compounds to Tackle Cardiovascular Disease and Diabetic Complications.

作者信息

Nenna Antonio, Spadaccio Cristiano, Lusini Mario, Ulianich Luca, Chello Massimo, Nappi Francesco

机构信息

Cardiac Surgery, Centre Cardiologique du Nord de Saint-Denis, 36 Rue des Moulins, Gémeaux, 93200 Saint-Denis, France.

出版信息

Recent Adv Cardiovasc Drug Discov. 2015;10(1):10-33. doi: 10.2174/1574890110666151104120039.

Abstract

Diabetes is a major risk factor for cardiovascular disease, and recent advances in research indicate that a detailed understanding of the pathophysiology of its effects is mandatory to reduce diabetes-related mortality and morbidity. Advanced Glycation End Products (AGEs) play a central role in the genesis and progression of complications of both type 1 and type 2 diabetes mellitus, and have been found to be important even in non-diabetic patients as a marker of cardiovascular disease. AGEs have a profound impact on patient's prognosis regardless of the glycemic control, and therefore pharmacologic approaches against AGEs accumulation have been proposed over the years to treat cardiovascular diseases, parallel to a more detailed understanding of AGEs pathophysiology. Compounds with anti-AGEs effects are currently under investigation in both pre-clinical and clinical scenarios, and many of the drugs previously used to treat specific diseases have been found to have AGE-inhibitory effects. Some products are still in "bench evaluation", whereas others have been already investigated in clinical trials with conflicting evidences. This review aims at summarizing the mechanisms of AGEs formation and accumulation, and the most relevant issues in pre-clinical and clinical experiences in anti-AGEs treatment in cardiovascular research.

摘要

糖尿病是心血管疾病的主要危险因素,近期的研究进展表明,要降低糖尿病相关的死亡率和发病率,必须详细了解其作用的病理生理学。晚期糖基化终产物(AGEs)在1型和2型糖尿病并发症的发生和发展中起核心作用,并且已发现其在非糖尿病患者中作为心血管疾病的标志物也很重要。无论血糖控制情况如何,AGEs对患者的预后都有深远影响,因此多年来人们提出了针对AGEs积累的药物治疗方法来治疗心血管疾病,同时也对AGEs的病理生理学有了更详细的了解。目前正在临床前和临床研究中对具有抗AGEs作用的化合物进行研究,并且已发现许多先前用于治疗特定疾病的药物具有AGE抑制作用。一些产品仍处于“实验室评估”阶段,而其他产品已经在临床试验中进行了研究,但证据相互矛盾。本综述旨在总结AGEs形成和积累的机制,以及心血管研究中抗AGEs治疗的临床前和临床经验中的最相关问题。

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