PMID:
Life Sci. 2019 Oct 8 ;237:116943. Epub 2019 Oct 8. PMID: 31604109
Abstract Title:
Artemisinin attenuates the development of atherosclerotic lesions by the regulation of vascular smooth muscle cell phenotype switching.
Abstract:
AIMS: 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).MAIN METHODS: Eight-week-old male ApoEmice 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.KEY FINDINGS: Artemisinin treatment significantly reduced plaque area in the ApoEmice 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.SIGNIFICANCE: 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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