Abstract

APIP is a key regulator of AF following MI. • APIP overexpression attenuates atrial remodeling and AF. • APIP is a promising therapeutic target for AF. Background Atrial fibrillation (AF), the most prevalent form of cardiac arrhythmia, frequently develops as a complication of acute myocardial infarction (MI). Nonetheless, the temporal dynamics of gene expression and key signaling pathways implicated in the development of AF following MI remain elusive. Methods Male wild-type C57BL/6 mice were subjected to coronary artery ligation to induce MI for 1, 3, or 7 days. AF inducibility, atrial diameter, and pathological alterations were examined using programmed intracardiac stimulation, echocardiography, and histological staining. Temporal gene expression profiles were analyzed via microarray analysis. Results A total of 3364 differentially expressed genes (DEGs) were identified in atrial tissues at 1, 3, and 7 days post-MI compared to sham controls. These DEGs were primarily associated with mitochondrial function and the citrate cycle (TCA cycle) in atrial tissues following MI. Furthermore, co-expression network analysis revealed that APAF1-interacting protein (APIP) was centrally positioned in the gene co-expression network. Moreover, its expression was significantly downregulated in atrial tissues across various time points following MI. Cardiomyocyte-specific overexpression of APIP significantly attenuated atrial remodeling and fibrillation following MI. These beneficial effects were accompanied by elevated Mfn1/Mfn2 and p-Drp1(S637) levels, reduced Drp1 expression levels, and enhanced mitochondrial function. Finally, APIP upregulated citrate synthase (CS), enhanced respiratory complexes I-V, and significantly increased ATP synthesis. Conclusions This study systematically characterized temporal changes in differentially expressed genes (DEGs) associated with AF following MI and highlights the protective role of APIP in mitigating AF development post-MI, positioning