Abstract
Family with sequence similarity 3 member A (FAM3A) is a multifunctional protein that is related to the pathological process of various disorders. FAM3A is reportedly able to affect the phenotypic change of vascular smooth muscle cells under a hypertensive state. Whether FAM3A mediates the phenotypic switch of vascular smooth muscle cells under an atherosclerotic state remains unaddressed. This work investigated the roles and mechanisms of FAM3A in mediating the phenotypic switch of human aortic smooth muscle cells (HASMCs) stimulated with oxidised low-density lipoprotein (ox-LDL) in vitro. FAM3A expression was elevated in HASMCs following ox-LDL treatment. FAM3A silencing led to a suppressive effect on ox-LDL-provoked proliferation, migration and inflammation of HASMCs, whereas FAM3A overexpression had an opposite effect. Ox-LDL elicited a change in HASMCs from a contractile phenotype to a synthetic phenotype, which was inhibited by FAM3A silencing or enhanced by FAM3A overexpression. Further investigation elucidated that FAM3A silencing repressed and FAM3A overexpression promoted ox-LDL-induced activation of the PI3K-AKT pathway in HASMCs. Reactivation of AKT reversed the suppressive effect of FAM3A silencing on the ox-LDL-induced phenotypic switch of HASMCs. Restraining AKT blocked the promoting effect of FAM3A overexpression on the ox-LDL-induced phenotypic switch of HASMCs. In summary, this work elucidates that FAM3A mediates the ox-LDL-induced phenotypic switch of HASMCs by influencing the PI3K-AKT pathway, indicating a potential role for FAM3A in atherosclerosis.