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胰岛素抵抗、氧化应激与心血管并发症:沉默信息调节因子的作用。

Insulin resistance, oxidative stress and cardiovascular complications: role of sirtuins.

机构信息

Division of Pharmacology, Indian Institute of Chemical Technology (IICT), Hyderabad-500607, India.

出版信息

Curr Pharm Des. 2013;19(32):5663-77. doi: 10.2174/13816128113199990372.

Abstract

Cardiovascular disease (CVD) is one of the major lifestyle associated disorders and leading causes of death worldwide. The incidence of CVD in diabetic patients has increased up to 3 folds and it became the major risk for diabetes associated morbidity and mortality. Insulin resistance and oxidative stress both play a central role in the pathogenesis and progression of diabetes. The high prevalence of CVD among diabetic patients suggests the role of insulin resistance and oxidative stress in developing cardiovascular complications. Finding molecular mechanisms which could control both insulin resistance and oxidative stress would be more efficacious in improving the cardiovascular complications. Recent literatures show that an epigenetic mechanism could control or regulate the cardiovascular complications in diabetes. Sirtuins, a group of enzymes, modulate epigenetic changes by deacetylating histone and non-histone proteins. These enzymes are distributed in different cell organelles and are found to regulate different biological processes. Recent findings showed that sirtuins modulate different important proteins related to insulin signaling pathway and oxidative stress. This review summarizes how sirtuins could affect the insulin resistance and oxidative stress pathways in cardiovascular system and thus attenuate the cardiovascular complications. Understanding the role of sirtuins in insulin resistance and oxidative stress will increase the prospects for controlling or preventing cardiovascular complications in the future.

摘要

心血管疾病(CVD)是与生活方式相关的主要疾病之一,也是全球范围内主要的死亡原因。糖尿病患者的 CVD 发病率增加了 3 倍,成为糖尿病相关发病率和死亡率的主要危险因素。胰岛素抵抗和氧化应激在糖尿病的发病机制和进展中都起着核心作用。糖尿病患者中 CVD 的高患病率表明胰岛素抵抗和氧化应激在发展心血管并发症中的作用。寻找既能控制胰岛素抵抗又能控制氧化应激的分子机制,将更有效地改善心血管并发症。最近的文献表明,表观遗传机制可以控制或调节糖尿病中的心血管并发症。组蛋白去乙酰化酶 sirtuins 是一组酶,通过去乙酰化组蛋白和非组蛋白来调节表观遗传变化。这些酶分布在不同的细胞细胞器中,被发现调节不同的生物学过程。最近的研究发现,sirtuins 调节与胰岛素信号通路和氧化应激相关的不同重要蛋白质。本综述总结了 sirtuins 如何影响心血管系统中的胰岛素抵抗和氧化应激途径,从而减轻心血管并发症。了解 sirtuins 在胰岛素抵抗和氧化应激中的作用将增加未来控制或预防心血管并发症的前景。

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