Artesunate inhibits macrophage-like phenotype switching of vascular smooth muscle cells and attenuates vascular inflammatory injury in atherosclerosis<i> via</i> NLRP3

作者全名："Liu, Ping; Wang, Yuqi; Tian, Keke; Bai, Xinyu; Wang, Yaowen; Wang, Yan"

作者地址："[Liu, Ping; Wang, Yuqi; Tian, Keke; Bai, Xinyu; Wang, Yan] Zunyi Med Univ, Key Lab Basic Pharmacol, Joint Int Res Lab Ethnomed, Minist Educ, Zunyi 563000, Peoples R China; [Wang, Yaowen] Chongqing Med Univ, Chongqing Cardiac Arrhythmias Therapeut Serv Ctr, Dept Cardiol, Affiliated Hosp 2, Chongqing 400010, Peoples R China"

通信作者："Wang, Y (通讯作者)，Zunyi Med Univ, Key Lab Basic Pharmacol, Joint Int Res Lab Ethnomed, Minist Educ, Zunyi 563000, Peoples R China.; Wang, YW (通讯作者)，Chongqing Med Univ, Chongqing Cardiac Arrhythmias Therapeut Serv Ctr, Dept Cardiol, Affiliated Hosp 2, Chongqing 400010, Peoples R China."

来源：BIOMEDICINE & PHARMACOTHERAPY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001185160400001

JCR分区：Q1

影响因子：7.5

年份：2024

卷号：172

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Artesunate; Atherosclerosis; HVSMCs; Macrophage -like phenotype switch; Heparinase

摘要："Inflammation is one of the main pathogenic factors of atherosclerosis (AS), and the phenotypic transformation of macrophages in human vascular smooth muscle cells (HVSMCs) contributes to the inflammatory injury of blood vessels and the formation of atherosclerotic plaques. Artesunate reportedly exerts anti-inflammatory activity against AS. Herein, we aimed to explore the artesunate-mediated anti-inflammatory and HVSMC phenotypic switch effects against AS and elucidate potential underlying mechanisms. In vitro, artesunate decreased expression of NLRP3, caspase-1, and interleukin (IL)- 18. Artesunate significantly inhibited low -density lipoprotein (LDL) expression in HVSMCs and macrophages. In vivo, artesunate reduced atherosclerotic plaque formation in high -fat diet (HFD)-fed ApoE-/- mice, as well as decreased NLRP3 and CD68 expression in atherosclerotic plaques. Artesunate decreased serum levels of triglycerides and increased high -density lipoprotein levels in HFD-med mice; however, serum levels of total cholesterol and LDL were unaltered. Treatment with artesunate substantially increased alpha-smooth muscle actin expression in aortic tissues while inhibiting expression levels of NLRP3, IL -18, heparinase, matrix metalloproteinase 9, and Kruppel-like factor 4 (KLF4). Collectively, our findings suggest that artesunate-mediated effects may involve inhibition of the ERK1/2/NF-kappa B/IL-18 pathway in HVSMCs via the downregulation of NLRP3 expression. Thus, artesunate could serve as a novel strategy to treat AS by inhibiting AS plaque formation and suppressing macrophage -like phenotype switching of HVSMCs."

基金机构："National Natural Science Foundation of China [81860643]; Basic Research Program (Natural Science) of the Guizhou Provincial Department of Science and Technology [qiankehejichu-ZK [2022] yiban599, qiankehejichu-ZK (2023) yiban505]"

基金资助正文：This work was supported by the National Natural Science Foundation of China (No. 81860643) and Basic Research Program (Natural Science) of the Guizhou Provincial Department of Science and Technology [No. qiankehejichu-ZK [2022] yiban599 and qiankehejichu-ZK (2023) yiban505] .