Fibrinopeptide a promotes the proliferation and migration of vascular smooth muscle cells by regulating the integrin αVβ3/PI3K/AKT signaling pathway

BackgroundAtherosclerosis is characterized by subintimal proliferation and migration of vascular smooth muscle cells (VSMCs) in response to stimuli such as coagulation and inflammatory factors. Fibrinopeptide A (FPA), a biomarker for coagulation system activation, is elevated in patients with ischemic heart disease. However, its role in the pathophysiology of cardiovascular disorders remains unclear. This study aimed to investigate the impact of FPA on VSMCs proliferation and migration and elucidate the underlying molecular mechanisms.Methods and resultsTranscriptome sequencing and bioinformatics analysis were employed to elucidate molecular pathways. Scratch wound and Transwell assays were performed to evaluate cell migration capacity. Molecular expression patterns were assessed using immunofluorescence, real-time quantitative PCR, and Western blot assays. The differentially expressed genes (DEGs) in the FPA-treated VSMCs were enriched in the cell cycle and PI3K/AKT signaling pathway. FPA treatment enhanced VSMCs' migratory capacity and upregulated integrin alpha V beta 3, PI3K, P-AKT, AKT, Cyclin D1, and PCNA expression. The integrin alpha V beta 3 inhibitor Cyclo-RGDfk effectively suppressed VSMCs migration and reduced the expression levels of these genes in FPA-stimulated VSMCs.ConclusionsThese results suggested that FPA promotes the proliferation and migration of VSMCs by regulating the PI3K/AKT signaling pathway through integrin alpha V beta 3.