Artemisinin attenuates the development of atherosclerotic lesions by the regulation of vascular smooth muscle cell phenotype switching
2019
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 ApoE−/- mice were treated with ART for eight weeks. Atherosclerotic lesion sizes were determined by
Oil Red Ostaining, and
RNA-Seqwas used to detect the profile of differentially expressed genes following the administration of ART. The expressions of
contractilephenotypic 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
Artemisinintreatment significantly reduced plaque area in the ApoE−/- mice and increased the expression of
contractilephenotypic markers.
RNA-Seqof 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
contractilefunction. 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
contractilephenotype. 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 musclecell
phenotype switchingto 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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