The underlying mechanisms of FGF2 in carotid atherosclerotic plaque development revealed by bioinformatics analysis.

Introduction: The purpose of this study was to explore the regulatory mechanisms of FGF2 in carotid atherosclerotic plaque development using bioinformatics analysis. Material and methods: Expression profiles of 32 atheroma plaque (AP) and 32 paired distant macroscopically intact (DMI) tissues samples in the GSE43292 dataset were downloaded from the Gene Expression Omnibus database. Following identification of differential expression genes (DEGs), correlation analysis of fibroblast growth factor 2 (FGF2) and DEGs was conducted. Subsequently, functional enrichment analysis and the protein-protein interaction network for FGF2 significantly correlated DEGs were constructed. Then, microRNAs (miRNAs) that regulated FGF2 and regulatory pairs of long noncoding RNA (lncRNA)-miRNA were predicted to construct the lncRNA-miRNA-FGF2 network. Results: A total of 101 DEGs between AP and DMI samples were identified, and 31 DEGs were analyzed to have coexpression relationships with FGF2, including 23 positively correlated and 8 negatively correlated DEGs. VAV3 had the lowest r value among all FGF2 negatively correlated DEGs. FGF2 positively correlated DEGs were closely related to "regulation of smooth muscle contraction" (e.g., calponin 1 (CNN1)), while FGF2 negatively correlated DEGs were significantly associated with "platelet activation" (e.g., Vav guanine nucleotide exchange factor 3 (VAV3)). In addition, a total of 12 miRNAs that regulated FGF2 were predicted, and hsa-miR-15a-5p and hsa-miR-16-5p were highlighted in the lncRNA-miRNA-FGF2 regulatory network. Conclusions: CNN1 might cooperate with FGF2 to regulate smooth muscle contractility during CAP formation. VAV3 might cooperate with FGF2 to be responsible for the development of CAP through participating in platelet activation. Hsa-miR-15a-5p and hsa-miR-16-5p might participate in the development of CAP via regulating FGF2.