文献类型：期刊文献

英文题名：Pseudane V alleviates ox-LDL-induced macrophage M1 polarization by inhibiting m6A modification of PPARGC1A

作者：Li, Tao[1];Pang, Qi[2];Pan, Jun[3];Gao, Ya[1];Huang, Yuan[1];Tian, Wei[4];Ran, Junchuan[1];Zhu, Zheng[1];Liu, Yongbin[1];Li, Kunsheng[3]

第一作者：李婷

通信作者：Li, KS[1]

机构：[1]Gansu Univ Chinese Med, Lanzhou Petrochem Gen Hosp, Affiliated Hosp 4, Dept Cardiol, Lanzhou 730060, Peoples R China;[2]Gansu Univ Chinese Med, Lanzhou Petrochem Gen Hosp, Affiliated Hosp 4, Dept Tradit Chinese Med, Lanzhou 730060, Peoples R China;[3]Nanjing Univ, Jiangsu Univ, Nanjing Drum Tower Hosp,Clin Coll, Dept Cardiothorac Surg,Affiliated Hosp,Med Sch, Nanjing 210008, Peoples R China;[4]Gansu Univ Chinese Med, Clin Med Coll 1, Grad Sch, Lanzhou 730000, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Nanjing Univ, Nanjing Drum Tower Hosp, Affiliated Hosp, Dept Cardiothorac Surg,Med Sch, 321 Zhongshan Rd, Nanjing 210008, Peoples R China.

年份：2026

卷号：454

期号：2

外文期刊名：EXPERIMENTAL CELL RESEARCH

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001633322800002)】；

基金：This work was supported by the Xigu District Science and Technology Bureau of Lanzhou (grant No. XGKJ-2024-016) , the Lanzhou Science and Technology Bureau (grant No. 2023-2-119) , the Health Commission of Gansu Province (grant No. GSWSKY2022-32) , the Education Department of Gansu Province (grant No. 2022B-110) , and Gansu Baoshihua Hospital (grant No. GSBSHYY-2022-01) , Clinical Trials from the Affiliated Drum Tower Hospital, Medical School of Nanjing University (2021-LCYJ-PY-31) , The High-level Innovation and Entrepreneurship Talent Introduction Plan of Jiangsu Province (JSSCBS20211507) , the project of China International Medical Foundation (2022-N-01-04) , the Research project on undergraduate education and teaching reform in the School of Integrated Medicine, School of Medicine, Nanjing University of Chinese Medicine (NZYYXY2023009) , and the 2022 Nanjing Post-Doctoral Research Funding Program

语种：英文

外文关键词：Pseudane V; Atherosclerosis; Macrophage; m6A; PPARGC1A

摘要：Atherosclerosis is driven by oxidized low-density lipoprotein (ox-LDL)-triggered macrophage malfunction, yet the precise pathways and effective counter-measures remain elusive. Here we delineated how N6-methyladenosine (m6A) RNA methylation governs ox-LDL-induced M1 macrophage polarization and evaluated marine natural products for therapeutic intervention. Human monocytic THP-1 cells differentiated into M0 macrophages were treated with ox-LDL. M1/M2 polarization states were analyzed using flow cytometry, and changes in polarization markers were examined using quantitative real-time polymerase chain reaction (qRT-PCR). Global m6A changes were detected using m6A dot blot and quantification analysis. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) were performed to identify downstream target genes of the ox-LDL-m6A pathway. The role of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) in ox-LDL-induced M1 polarization was analyzed. A high-throughput marine natural product library was employed to discover agents capable of reversing ox-LDL-driven macrophage polarization. ox-LDL induces macrophage M1 polarization, and M1 macrophages damage endothelial cells. ox-LDL-induced polarization of macrophages into the M1 phenotype was associated with increased global RNA m6A modification. High levels of m6A modification induced by ox-LDL suppressed PPARGC1A expression in a YTH domain family 2 (YTHDF2)-dependent manner, leading to M1 polarization. Pseudane V, a marine natural product, effectively reduced ox-LDL-induced M1 polarization and protected vascular endothelial cells by correcting abnormal m6A modification of PPARGC1A. In conclusion, ox-LDL induces m6A modification of PPARGC1A, suppressing its expression and promoting M1 polarization of macrophages, contributing to atherosclerosis development. Pseudane V counteracts excessive m6A modification caused by ox-LDL, preventing M1 polarization of macrophages. These findings suggest the potential use of Pseudane V in preventing atherosclerosis.