Abstract

Background Atrial fibrillation (AF) is a common arrhythmia associated with myocardial injury, oxidative stress, and inflammatory remodeling. Mitochondrial protein CR6-interacting factor 1 (CRIF1) has emerged as a potential regulator of cardiomyocyte homeostasis; however, its role in AF remains unclear. Methods An AF model was established in C57BL/6 mice via subcutaneous infusion of angiotensin II (Ang II, 2.0 mg/kg/day) for 28 days. CRIF1 expression levels and its functional effects were evaluated in atrial tissue and Ang II-treated HL-1 cardiomyocytes using RT-qPCR, immunohistochemistry, ELISA, TUNEL, and DHE staining. CRIF1 was overexpressed to assess its effects on the SIRT1/eNOS pathway, apoptosis, hypertrophy, inflammation, and oxidative stress. Results Ang II infusion promoted atrial remodeling and increased susceptibility to atrial fibrillation. During electrophysiological assessment, AF episodes were triggered by transesophageal burst pacing, revealing prolonged AF duration, increased AF inducibility, elevated creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) levels, and enhanced atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) expression in Ang II-treated mice compared with controls. CRIF1 expression was markedly downregulated in the atrial tissue of AF mice and Ang II-treated HL-1 cells. CRIF1 overexpression activates the SIRT1/eNOS pathway, attenuates cardiomyocyte apoptosis, and reduces Ang II–induced hypertrophy. Furthermore, CRIF1 suppressed the expression of inflammatory cytokines (TNF-α, IL-1β, and IL-6) and diminished intracellular reactive oxygen species accumulation, thereby restoring antioxidant enzyme activity and nitric oxide (NO) production. The protective effects of CRIF1 on apoptosis are largely dependent on SIRT1 signaling.