摘要Uncontrolled proliferation,migration and phenotypic switching of vascular smooth muscle cells(VSMCs)are im-portant steps in the development and progression of aortic dissection(AD).The function and potential mechanism of miR-335-5p in the pathogenesis of AD are explored in this study.Specifically,the biological function of miR-335-5p is explored in vitro through CCK-8,Transwell,immunofluorescence,EdU,wound-healing,RT-qPCR and western blotting assays.In addition,an AD model induced by angiotensin Ⅱ is used to investigate the function of miR-335-5p in vivo.A dual-luciferase assay is performed to verify the targeting relationship between miR-335-5p and specificity protein 1(SP1).Experiments involving the loss of SP1 function are performed to demonstrate the function of SP1 in the miR-335-5p-mediated regulation of human aortic-VSMCs(HA-VSMCs).AD tissues and platelet-derived growth factor BB(PDGF-BB)-stimulated HA-VSMCs show significant downregulation of miR-335-5p expression and upre-gulated SP1 expression.Overexpression of miR-335-5p effectively suppresses cell proliferation,migration and synthetic phenotype markers and enhances contractile phenotype markers induced by PDGF-BB treatment.Ad-ditionally,SP1 is identified as a target gene downstream of miR-335-5p,and its expression is negatively correlated with miR-335-5p in AD.Upregulation of SP1 partially reverses the inhibitory effect of miR-335-5p on HA-VSMCs,whereas the downregulation of SP1 has the opposite effect.Furthermore,Ad-miR-335-5p clearly suppresses aorta dilatation and vascular media degeneration in the AD model.Our results suggest that miR-335-5p inhibits HA-VSMC proliferation,migration and phenotypic switching by negatively regulating SP1,and indicate that miR-335-5p may be a potential therapeutic target in AD.