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动脉粥样硬化管理的范式转变:沉默调节蛋白在动脉粥样硬化中的保护作用。

A Paradigm Shift in the Management of Atherosclerosis: Protective Role of Sirtuins in Atherosclerosis.

作者信息

Toulassi Ijeoma A, Al Saedi Usama A, Gutlapalli Sai Dheeraj, Poudel Sujan, Kondapaneni Varshitha, Zeb Mehwish, Cancarevic Ivan

机构信息

Pathology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA.

Dentistry, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA.

出版信息

Cureus. 2021 Jan 16;13(1):e12735. doi: 10.7759/cureus.12735.

Abstract

Facing the rise of an aging population and age-related pathologies such as atherosclerosis will continue to be some of the biggest challenges encountering health care. Regardless of considerable advancements in management and prevention to deal with atherosclerosis and other related pathologies. The current guidelines for preventing and managing atherosclerotic diseases are lifestyle changes, blood pressure control, blood glucose control, and lipid control. There has been an increase in pre-clinical studies regarding the effects of sirtuins on atherosclerosis and this review aims to highlight the benefits of sirtuins in atherosclerosis. We did an extensive search using the PubMed database with the medical subject headings (MeSH) keywords "sirtuin'' and "atherosclerosis." The reviewed literature reported that sirtuins prevent and ameliorate atherosclerosis by halting inflammation, apoptosis, oxidative stress, and regulating low-density lipoprotein (LDL) cholesterol. Sirtuin 1 (SIRT1) and sirtuin 6 (SIRT6) inhibit the RELA component of NF-kB, thus suppressing inflammation, SIRT1 inhibits p53 by deacetylation, and the latter stabilize telomeres thus preventing apoptosis and cell death. Sirtuin 3 (SIRT3) inhibits oxidative stress by driving the production of reduced glutathione. Sirtuin 2 (SIRT2) regulates LDL cholesterol by inhibiting pcsk9, increasing LDL receptors on the cell surface of hepatocytes. A combination of these effects of sirtuins in the endothelial cells suggests sirtuins are anti-atherogenic and could revolutionize the standards for the management of atherosclerosis. This article also emphasizes the need for future research on human cells or subjects rather than animal subjects.

摘要

面对人口老龄化的加剧,诸如动脉粥样硬化等与年龄相关的病症将继续成为医疗保健领域面临的一些最大挑战。尽管在动脉粥样硬化及其他相关病症的管理和预防方面取得了显著进展,但目前预防和管理动脉粥样硬化疾病的指南包括生活方式改变、血压控制、血糖控制和血脂控制。关于沉默调节蛋白对动脉粥样硬化影响的临床前研究有所增加,本综述旨在强调沉默调节蛋白在动脉粥样硬化中的益处。我们使用PubMed数据库,以医学主题词(MeSH)关键词“沉默调节蛋白”和“动脉粥样硬化”进行了广泛搜索。综述文献报道,沉默调节蛋白通过阻止炎症、细胞凋亡、氧化应激以及调节低密度脂蛋白(LDL)胆固醇来预防和改善动脉粥样硬化。沉默调节蛋白1(SIRT1)和沉默调节蛋白6(SIRT6)抑制核因子κB的RELA成分,从而抑制炎症,SIRT1通过去乙酰化作用抑制p53,而p53可稳定端粒,从而防止细胞凋亡和细胞死亡。沉默调节蛋白3(SIRT3)通过促进还原型谷胱甘肽的产生来抑制氧化应激。沉默调节蛋白2(SIRT2)通过抑制前蛋白转化酶枯草溶菌素9(pcsk9)来调节LDL胆固醇,增加肝细胞表面的LDL受体。沉默调节蛋白在内皮细胞中的这些作用综合起来表明,沉默调节蛋白具有抗动脉粥样硬化作用,可能会彻底改变动脉粥样硬化的管理标准。本文还强调了未来对人体细胞或受试者而非动物受试者进行研究的必要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81b3/7883534/3183719eb802/cureus-0013-00000012735-i01.jpg

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