Knockdown of ALOX15 alleviates acute coronary syndrome via the FGFR2/PI3K/AKT signaling pathway

Acute coronary syndrome (ACS) is a serious cardiovascular condition and a leading cause of mortality worldwide. Notably, 12/15-lipoxygenase (ALOX15) can be regulated by the long non-coding RNA ENST00000538705.1, thereby facilitating the progression of ACS. However, the downstream regulatory mechanisms involving ALOX15 remain unclear. The viability and migration of human primary coronary artery endothelial cells (HCAECs) were assessed using the Cell Counting Kit-8 and scratch assays, respectively. Reverse transcription-quantitative PCR was performed to assess the mRNA expression levels of ALOX15 and fibroblast growth factor receptor 2 (FGFR2). Protein-protein interactions between ALOX15 and FGFR2 were verified by co-immunoprecipitation (CO-IP). An ACS rat model was established to examine the effects of ALOX15 on blood lipid levels. Hematoxylin and eosin staining was executed to assess the histological changes. The levels of the FGFR2/PI3K/AKT signaling pathway-related proteins were assessed by western blotting. The results revealed elevated expression levels of ALOX15 and FGFR2 in patients with ACS. In HCAECs, transfection of overexpressed ALOX15 markedly enhanced cell viability and migration, while small interfering RNA-ALOX15 transfection produced the opposite effects. CO-IP assays confirmed the interaction between ALOX15 and FGFR2 in HCAECs. Additionally, knockdown of ALOX15 reduced blood lipid levels and alleviated myocardial injury in rats with ACS. ALOX15 silencing inhibited the expression of proteins associated with the FGFR2/PI3K/AKT signaling pathway in both HCAECs and rats with ACS. Both the overexpression of FGFR2 and the supplementation with insulin like growth factor 1 (a specific agonist of the PI3K/AKT pathway) significantly mitigated the inhibitory effects of ALOX15 knockdown on the migratory and proliferative capacities of HCAECs. The findings of the present study indicated that silencing of ALOX15 alleviates ACS progression via inhibiting the FGFR2/PI3K/AKT signaling pathway, providing a theoretical basis for ACS therapy in clinic.