FIZZ1 Promotes Atherosclerosis by Enhancing Proliferation, Migration, and Angiogenesis of Aortic Endothelial Cells

Background: Atherosclerosis is one of the primary causes of cardiovascular diseases. Previous studies have demonstrated the significant role of the Found in Inflammatory Zone 1 (FIZZ1) in the development of atherosclerosis. Therefore, this study aims to explore the potential mechanisms of FIZZ1 in atherosclerosis. Methods: The mouse aortic endothelial cells were utilized in the present study. The quantitative reverse transcription polymerase chain reaction (RT-qPCR) and RNA sequencing approaches were employed to assess the impact of FIZZ1 on vascular generationrelated genes as well as the expression of differentially expressed genes (DEGs) in endothelial cells. Furthermore, gene functional annotation and pathway enrichment analyses were conducted using the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis for FIZZ1-induced differentially expressed genes (DEGs). Additionally, Cell Counting Kit-8 and 5-ethynyl-20-deoxyuridine (EdU) assays were utilized to investigate the effect of FIZZ1 on cell proliferation. Transwell assay was used to evaluate cell migration, and angiogenesis assay was used to assess cell angiogenesis. Results: FIZZ1 treatment significantly downregulated the expression levels of angiogenesis-inhibiting genes such as Collagen Type I Alpha 1 Chain (COL1A1) and Endothelin Receptor Type A (EDNRA) while upregulated the expressions levels of angiogenesis-promoting genes including Fms Related Receptor Tyrosine Kinase 4 (FLT4) and Integrin Subunit Alpha 3 (ITGA3) (p < 0.05, and p < 0.01). Furthermore, FIZZ1 treatment substantially increased the proliferation, migration, and angiogenesis of aortic endothelial cells (p < 0.05, p < 0.01, and p < 0.001). Additionally, FIZZ1-induced DEGs were associated with crucial cellular functions which positively participate in cell proliferation, migration, and angiogenesis. Conclusion: In summary, FIZZ1 treatment can promote the proliferation, migration, and angiogenesis of aortic endothelial cells. Furthermore, it can induce numerous differentially expressed genes involved in angiogenesis-related functions or pathways. Consequently, FIZZ1 promotes the angiogenesis of aortic endothelial cells, thereby contributing to the progression of atherosclerosis. Therefore, FIZZ1 can serve as a potential therapeutic target for ameliorating atherosclerosis.