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PPAR gamma GENE AND ATHEROSCLEROSIS: GENETIC POLYMORPHISMS, EPIGENETICS AND THERAPEUTIC IMPLICATIONS

机译:PPARγ基因和动脉粥样硬化:遗传多态性,表观症和治疗意义

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摘要

Atherosclerosis is the leading cause of mortality and morbidity in the developed world. It is characterized by the formation of a plaque in the walls of middle and large arteries leading to macrovascular complications. Several risk factors are included, with diabetes being one of the most important for the onset and development of atherosclerosis. Due to an increase in the prevalence of diabetes in the world, the incidence of diabetic complications (microvascular and macrovascular) is increasing. Peroxisome proliferator-activated receptor gamma (PPAR gamma) plays a important role in atherosclerotic processes. Peroxisome proliferator activated receptor gamma belongs to the superfamily of nuclear receptors, has a great presence in fat tissue, macrophages, and regulates gene expression and most of the processes that lead to the onset and development of atherosclerosis. In this review, we discuss the basic patho-physiological mechanisms of atherosclerosis in type 2 diabetes mellitus (T2DM). Furthermore, we discuss the impact of PPARy polymorphisms, and the epigenetic mechanisms affecting the onset of atherosclerosis, i.e., DNA methylation and demethylation, histone acetylation and deacetylation, and RNA-based mechanisms. Moreover. we add therapeutic possibilities for acting on epigenetic mechanisms in order to prevent the onset and progression of atherosclerosis.
机译:动脉粥样硬化是发达国家死亡率和发病率的主要原因。它的特征在于形成中部和大动脉壁中的斑块,导致大血管并发症。包括一些危险因素,糖尿病是对动脉粥样硬化的发作和发展最重要的因素之一。由于世界上糖尿病患病率的增加,糖尿病并发症的发生率(微血管和大血管)正在增加。过氧化物体增殖物激活的受体γ(PPARγ)在动脉粥样硬化过程中起重要作用。过氧化物体增殖剂活化受体γ属于核受体的超家族,在脂肪组织,巨噬细胞中具有很大的存在,并调节基因表达以及导致动脉粥样硬化发作和发育的大部分过程。在本文中,我们讨论了2型糖尿病(T2DM)中动脉粥样硬化的基本病理生理机制。此外,我们讨论了PPARγ多态性的影响,以及影响动脉粥样硬化,即DNA甲基化和去甲基化,组蛋白乙酰化和脱乙酰化的表观遗传机制,以及基于RNA的机制。而且。我们为在表观遗传机制上添加治疗可能性,以防止动脉粥样硬化的发作和进展。

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