GABARAPL1 Exerts Regulatory Effects on Hypoxia‐Induced Pyroptosis in the Pathogenesis of Myocardial Infarction

• DOI: 10.1111/jcmm.70469
• Publication Date: 2025-03-17T16:40:33Z
• Authors: Chunying Liu; Chenghui Yan; Dan Liu; Haixu Song; Yaling Han

ABSTRACTMyocardial infarction (MI) is a major health threat, with high incidence and poor prognosis. This study aims to discover novel biomarkers and therapeutic targets to reduce myocardial damage and improve patient survival. A comprehensive bioinformatics analysis of MI datasets was conducted to identify pivotal genes related to pyroptosis and autophagy. These genes underwent protein–protein interaction (PPI) analysis, functional enrichment analysis, and immune infiltration analysis. Receiver operating characteristic (ROC) curves and nomograms were used to pinpoint the most diagnostic hub genes. Western blotting and qRT‐PCR were performed to evaluate their expression and mechanisms. Drug prediction and molecular docking identified potential therapeutic agents targeting hub genes, with validation of their effects on hypoxia‐induced pyroptosis both in vivo and in vitro. In conclusion, GABARAPL1 was identified as a hub gene, and PIK90 emerged as a promising therapeutic candidate drug. GABARAPL1 expression was significantly upregulated in heart tissue following MI and in endothelial cells subjected to hypoxic conditions. Silencing GABARAPL1 aggravated hypoxia‐induced pyroptosis in endothelial cells. In vivo, PIK90 improved survival, reduced cardiac dysfunction, and alleviated myocardial fibrosis induced by MI. In vitro, PIK90 inhibited hypoxia‐induced pyroptosis in endothelial cells. Consequently, GABARAPL1 may represent a promising therapeutic target for the treatment of MI.