Temporal gene expression profiling reveals the protective mechanism of APIP in atrial fibrillation following myocardial infarction

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 it as a therapeutic target for AF management.