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糖尿病血管内皮病变:RNA 结合蛋白作为新的治疗靶点。

Diabetic endotheliopathy: RNA-binding proteins as new therapeutic targets.

机构信息

The Wellcome-Wolfson Institute of Experimental Medicine, Queen's University Belfast, BT9 7BL, UK.

The Wellcome-Wolfson Institute of Experimental Medicine, Queen's University Belfast, BT9 7BL, UK.

出版信息

Int J Biochem Cell Biol. 2021 Feb;131:105907. doi: 10.1016/j.biocel.2020.105907. Epub 2020 Dec 26.

Abstract

Diabetic Endotheliopathy is widely regarded as a principal contributor to cardiovascular disease pathogenesis in individuals with Diabetes mellitus. The endothelium, the innermost lining of blood vessels, consists of an extensive monolayer of endothelial cells. Previously regarded as an interface, the endothelium is now accepted as an organ system with critical roles in vascular health; its dysfunction therefore is detrimental. Endothelial dysfunction induces blood vessel damage resulting in a restriction of blood and oxygen supply to tissues, the central pathology of cardiovascular disease. Hyperglycemic conditions have repeatedly been isolated as a pivotal inducer of endothelial cell dysfunction. Numerous studies have since proven hyperglycemic conditions to significantly alter the gene expression profile of endothelial cells, with this being largely attributable to the post-transcriptional regulation of RNA-binding proteins. In particular, the RBP Quaking-7 has recently emerged as a crucial mediator of diabetic endotheliopathy, with great potential to become a therapeutic target.

摘要

糖尿病血管病变被广泛认为是糖尿病患者心血管疾病发病机制的主要原因。血管内皮是血管的最内层,由一层广泛的内皮细胞组成。内皮曾被认为是一个界面,现在被认为是一个具有重要血管健康作用的器官系统;因此,它的功能障碍是有害的。内皮功能障碍导致血管损伤,从而限制血液和氧气供应到组织,这是心血管疾病的中心病理学。高血糖状态已被反复分离为内皮细胞功能障碍的关键诱导因素。此后,许多研究已经证明高血糖状态会显著改变内皮细胞的基因表达谱,这主要归因于 RNA 结合蛋白的转录后调控。特别是,RBP Quaking-7 最近作为糖尿病血管病变的关键介质出现,具有成为治疗靶点的巨大潜力。

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