Panoptosis Targets the Mechanism of PRDX1 Involvement in Acute Myocardial Infarction via ZBP1

ABSTRACT PANoptosis is involved in various pathological processes, but its role in acute myocardial infarction (AMI) remains unclear. This study aimed to explore the mechanism by which PANoptosis is involved in AMI. GSE172270 was used as an internal test set, and GSE159657 served as an external validation set to identify disease targets for AMI. WGCNA was performed to identify potential hub genes associated with AMI. Then, genes related to PANoptosis among the disease targets of AMI were screened. Additionally, human cardiomyocytes AC16 and mouse cardiomyocytes HL‐1 were cultured in sugar‐free and serum‐free medium for 4 h and 12 h, and the expression of key genes regulating PANoptosis was detected by qRT‐PCR. Finally, mRNA interference and overexpression experiments were conducted to verify the expression of key mRNAs. A total of 45 upregulated and 125 downregulated differentially expressed genes (DEGs) were identified in the GSE172270 data set. WGCNA identified 891 potential hub genes associated with AMI. In the GSE159657 data set, 695 upregulated and 552 downregulated DEGs were identified. Four genes related to AMI‐PANoptosis (PRDX1, MMACHC, BLVRB, and TXNL1) were screened. Through qRT‐PCR verification, PRDX1 was identified as the most specific and significant gene. The expression of the PANoptosis positive regulator ZPB1 was upregulated, while the PANoptosis negative regulator TAK1 was downregulated. Additionally, key cell death genes (MLKL, p‐MLKL, Caspase‐3, Caspase‐7, and GSDMD) were upregulated in sugar‐free and serum‐free culture. However, PRDX1 interference reversed these effects. Our study demonstrated that PRDX1 is a key regulator of PANoptosis in AMI.