中国动脉硬化杂志2023，Vol.31Issue(11)：945-957,13.DOI:10.20039/j.cnki.1007-3949.2023.11.004
circ-SKA3通过miR-1303调控TLR4轴在动脉粥样硬化中的作用
circ-SKA3 regulates the role of TLR4 axis in atherosclerosis through miR-1303
摘要
Abstract
Aim To explore the role of circular RNA spindle and kinetochore-associated protein 3(circ-SKA3)in regulating Toll-like receptor 4(TLR4)axis in atherosclerosis(As)through miR-1303.Methods Carotid artery plaque,diseased vascular tissue,normal tissue adjacent to plaque and venous blood were collected from 30 patients with As treated by carotid endarterectomy from April 2019 to April 2022.Another 30 normal venous blood samples were collected.Microarray analysis,quantitative real-time polymerase chain reaction(qRT-PCR)and fluorescence in situ hy-bridization(FISH)were used to detect the expression and localization of circ-SKA3 in plaque tissue of As patients,control samples,plasma exosome,human umbilical vein endothelial cell(HUVEC)and aorta of As model mice.The relationship among circ-SKA3,miR-1303 and TLR4 was verified by bioinformatics,double luciferase reporter gene detection and RNA immunoprecipitation.The proliferation,migration and angiogenesis of HUVEC were detected by CCK-8,scratch,Transwell and angiogenesis experiments.TLR4 axis-related protein expression was detected by Western blot-ting.Pathological changes of aorta in As model mice was observed by Oil red O staining,HE staining and Masson stai-ning.TLR4 expression in aorta of As model mice was detected by immunohistochemistry and immunofluorescence.Results The expression levels of circ-SKA3 and TLR4 in plaque tissue,plasma exosome,oxidized low density lipoprotein(ox-LDL)treated HUVEC and circ-SKA3,TLR4 in aortic of As model mice were up-regulated(P＜0.05),while the ex-pression level of miR-1303 was down-regulated(P＜0.05).Functional analysis showed that circ-SKA3 promoted HUVEC damage in vitro and As progress in vivo.Mechanism analysis showed that circ-SKA3 could promote TLR4 expression by adsorbing miR-1303 by sponge.Inhibition of circ-SKA3/miR-1303/TLR4 axis can inhibit the formation of As lesions.Conclusions circ-SKA3 is overexpressed in carotid plaque,plasma exosome,ox-LDL-treated HUVEC and As model mouse aorta in As patients.circ-SKA3/miR-1303/TLR4 axis can promote the development of As model in vivo and in vitro.关键词
环状RNA纺锤体与动粒相关蛋白3/miR-1303/Toll样受体4/动脉粥样硬化/氧化型低密度脂蛋白Key words
circular RNA spindle and kinetochore-associated protein 3/miR-1303/Toll-like receptor 4/ath-erosclerosis/oxidized low density lipoprotein分类
医药卫生引用本文复制引用
王克华,王金,王磊,任小璐,李颖..circ-SKA3通过miR-1303调控TLR4轴在动脉粥样硬化中的作用[J].中国动脉硬化杂志,2023,31(11):945-957,13.基金项目
宁夏医科大学2021年校级科研项目(XM2021001) （XM2021001）
