表型
血管平滑肌
油红O
表型转换
生物
转录组
细胞
载脂蛋白E
免疫印迹
基因表达
细胞生物学
基因
癌症研究
病理
医学
内分泌学
平滑肌
遗传学
脂肪生成
疾病
作者
Hongjiao Du,Zhao Qiao,Hongbin Zang,Cheng-Hsuan Chang,Xiao Dong Li
出处
期刊:Life Sciences
[Elsevier]
日期:2019-10-08
卷期号:237: 116943-116943
被引量:14
标识
DOI:10.1016/j.lfs.2019.116943
摘要
The purpose of this study was to investigate the therapeutic effect of artemisinin (ART) on atherosclerosis and explore the molecular mechanisms involved by RNA sequencing (RNA-Seq).Eight-week-old male ApoE-/- mice were treated with ART for eight weeks. Atherosclerotic lesion sizes were determined by Oil Red O staining, and RNA-Seq was used to detect the profile of differentially expressed genes following the administration of ART. The expressions of contractile phenotypic markers were detected by western blot and qRT-PCR, and the ability of the MOVAS cells to migrate and proliferate were assessed using the wound healing and CCK8 assays.Artemisinin treatment significantly reduced plaque area in the ApoE-/- mice and increased the expression of contractile phenotypic markers. RNA-Seq of aorta tissue revealed a distinct change in gene expression patterns after the mice were treated with ART. Our bioinformatics analysis demonstrated that the most prominently enriched pathway was a set of genes involved in vascular smooth muscle contractile function. Using an in vitro cell model, we demonstrated that ART could effectively reverse PDGF-activated MOVAS migration and proliferation, and elevate the level of proteins involved in the contractile phenotype.We provide in vivo and in vitro evidence supporting a role for ART in the suppression of atherosclerosis, partly through the inhibition of vascular smooth muscle cell phenotype switching to a de-differentiated phenotype. These data further advances our understanding for a potential role for ART and suggests that ART is an excellent candidate for the treatment of atherosclerosis.
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