关键词: 动脉粥样硬化, VAV1, 血管平滑肌细胞, 生物标志物, 收缩

Abstract: Objective To verify the expression of vav guanine nucleotide exchange factor 1 (VAV1) in the progression of atherosclerosis (AS) based on bioinformatics analysis and biological experiments and, to verify its potential regulatory role in vascular smooth muscle cells (VSMCs). Methods Three datasets of AS were obtained from Gene Expression Omnibus (GEO)and differentially expressed genes (DEGs) were identified. Hub genes were screened by GEO2R, Jvenn, STRING and Cytoscape. The expression and localization of VAV1 and SMMHC in vessels were detected by immuno-fluorescence staining(IFC).Western blot and real-time PCR were used to detect the expression of VAV1, SMMHC and SM22α. The contraction and proliferation of VSMCs were detected by collagen gel contraction assay and 5-ethynyl-2 deoxyuridine (EdU) staining. Results Totally 66 up-regulated genes and 88 down-regulated genes were identified in three datasets. Screening 10 Hub genes including VAV1 may be related to the progression of AS. IFC showed that the expression of VAV1 in AS plaque was significantly higher than that in normal vascular tissue (P＜0.05) and mainly located in VSMCs; Knocking down VAV1 promoted the contraction of VSMCs and inhibited its proliferation(P＜0.05). Conclusions The expression of VAV1 in AS plaques is increased, which is associated with the decreased contractility of VSMCs. VAV1 is a potential prognostic biomarker and therapeutic target of AS.

Key words: atherosclerosis, VAV1, vascular smooth muscle cell, biomarker, contraction