miR-144-3p Regulates Vascular Smooth Muscle Cell Phenotypic Switch via FBN1

Abstract Background: Carotid artery dissection (CAD) represents a commonly reported factor causing stroke in young and middle-aged adults. Vascular wall remodeling is one of its important pathogenetic mechanisms. FBN1 is a common pathogenic gene leading to Marfan syndrome, whose mutation can cause the formation of aneurysm and arterial dissection. It was recently demonstrated multiple miRNAs contribute to the development of arterial dissection, while miR-144-3p’s function is undefined.Methods: In the current study, vascular smooth muscle cells (VSMCs) were transfected with miR-144-3p mimic and inhibitor, as well as siFBN1 and miR-144-3p + siFBN1, to determine vascular smooth muscle’s contractile genes, extracellular matrix-associated proteins. In addition, miR-144-3p’s effects on cell proliferation, migration, adhesion, invasion and apoptosis were evaluated.Results: The results revealed miR-144-3p had elevated amounts, while the fibrillin-1 protein showed reduced expression in arterial dissection tissues. Meanwhile, FBN1 was shown to be a miR-144-3p target by dual-luciferase gene reporter assay. In response to miR-144-3p mimic transfection, decreased expression of VSMC contractile gene markers, increased apoptosis, and decreased proliferation, migration, and invasion were found.Conclusions: Overall, miR-144-3p affects the biological function of VSMCs by targeting and regulating FBN1, decreases the expression of contractile genes，transforms the phenotype and leads to vascular wall remodeling.