CircNPHP4 in monocyte-derived small extracellular vesicles controls heterogeneous adhesion in coronary heart atherosclerotic disease

作者全名："Xiong, Feng; Mao, Rui; Zhang, Lijuan; Zhao, Ruohan; Tan, Kunyue; Liu, Chunxia; Xu, JunBo; Du, Guanghong; Zhang, Tongtong"

作者地址："[Xiong, Feng; Zhang, Lijuan; Zhao, Ruohan; Tan, Kunyue; Liu, Chunxia; Xu, JunBo] Chengdu Third Peoples Hosp, Cadiovasc Inst Chengdu, Dept Cardiol, Chengdu 610031, Peoples R China; [Mao, Rui] Cent South Univ, Xiangya Hosp, Dept Dermatol, Changsha, Peoples R China; [Du, Guanghong] Sichuan Acad Med Sci & Sichuan Prov Peoples Hosp, Geriatr Dept, Chengdu 610072, Sichuan, Peoples R China; [Zhang, Tongtong] Southwest Jiaotong Univ, Affiliated Hosp, Peoples Hosp Chengdu 3, Med Res Ctr,Chengdu Hosp 2,Chongqing Med Univ, Chengdu 610031, Sichuan, Peoples R China; [Zhang, Tongtong] Southwest Jiaotong Univ, Affiliated Hosp, Peoples Hosp Chengdu 3, Dept Gen Surg,Ctr Gastrointestinal & Minimally In, Chengdu 610031, Peoples R China; [Zhang, Tongtong] Chongqing Med Univ, Affiliated Hosp 2, Chengdu 610031, Peoples R China"

通信作者："Xiong, F (corresponding author), Chengdu Third Peoples Hosp, Cadiovasc Inst Chengdu, Dept Cardiol, Chengdu 610031, Peoples R China.; Du, GH (corresponding author), Sichuan Acad Med Sci & Sichuan Prov Peoples Hosp, Geriatr Dept, Chengdu 610072, Sichuan, Peoples R China.; Zhang, TT (corresponding author), Southwest Jiaotong Univ, Affiliated Hosp, Peoples Hosp Chengdu 3, Med Res Ctr,Chengdu Hosp 2,Chongqing Med Univ, Chengdu 610031, Sichuan, Peoples R China.; Zhang, TT (corresponding author), Southwest Jiaotong Univ, Affiliated Hosp, Peoples Hosp Chengdu 3, Dept Gen Surg,Ctr Gastrointestinal & Minimally In, Chengdu 610031, Peoples R China.; Zhang, TT (corresponding author), Chongqing Med Univ, Affiliated Hosp 2, Chengdu 610031, Peoples R China."

来源：CELL DEATH & DISEASE

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000707370200005

JCR分区：Q1

影响因子：9

年份：2021

卷号：12

期号：10

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Small extracellular vesicles (sEVs)-derived circular RNAs (circRNAs) could regulate gene expression in recipient cells, and dysregulation of sEVs-derived circRNAs has been implicated in several diseases. However, the expression and function of sEVs-derived circRNAs in coronary heart atherosclerotic disease (CAD) remain unknown. In this study, we investigated global changes in the expression patterns of circRNAs in sEVs from CAD-related monocytes and identified circNPHP4 as a significantly upregulated circRNA. Knockdown of circNPHP4 inhibited heterogeneous adhesion between monocytes and coronary artery endothelial cells and reduced ICAM-1 and VCAM-1 expression. Investigations of the underlying mechanisms revealed that circNPHP4 contains a functional miR-1231-binding site. Mutation of the circNPHP4-binding sites in miR-1231 abolished the interaction, as indicated by a luciferase reporter assay. Furthermore, circNPHP4 affected the expression of miR-1231 and its target gene EGFR. Overexpression of miR-1231 blocked the inhibitory effect of circNPHP4 on heterogeneous adhesion. Moreover, downregulation of miR-1231 restored heterogeneous adhesion upon inhibition by circNPHP4 silencing. Additionally, circNPHP4 overexpression was correlated with aggressive clinicopathological characteristics in CAD patients. A multivariate logistic regression model and bootstrapping validation showed that circNPHP4 overexpression had a good risk prediction capability for CAD. The decision curve analysis revealed that using the CAD nomogram that included circNPHP4 overexpression to predict the risk of CAD was beneficial. Our results suggest that sEVs-derived circNPHP4 can serve as a potential target for CAD treatments or as a potential diagnostic marker for CAD patients."

基金机构："National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81502075]; Foundation of Science and Technology of Sichuan Province [2018JY0385, 2019YJ0635]; Foundation of Science and Technology of Chengdu City [2018-YF05-00185-SN]"

基金资助正文："This work was supported by grants from the National Natural Science Foundation of China (81502075), the Foundation of Science and Technology of Sichuan Province (2018JY0385 and 2019YJ0635) and the Foundation of Science and Technology of Chengdu City (2018-YF05-00185-SN)."