CRIF1 overexpression significantly attenuated Angiotensin II-induced atrial fibrillation susceptibility, cardiomyocyte apoptosis, and hypertrophy by activating the SIRT1/eNOS signaling pathway.
Does CRIF1 overexpression prevent Angiotensin II-induced atrial fibrillation and cardiomyocyte remodeling in preclinical models?
CRIF1 plays a protective role against Ang II-induced atrial remodeling and AF by activating SIRT1/eNOS signaling, highlighting it as a potential therapeutic target.
p-value: p=<0.001
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. Conclusion: CRIF1 plays a critical protective role in Ang II–induced atrial remodeling by activating SIRT1/eNOS signaling and mitigating oxidative stress, inflammation, hypertrophy, and apoptosis. These findings highlight CRIF1 as a potential therapeutic target for preventing AF and its associated cardiac injuries. Keywords: atrial fibrillation, CRIF1, SIRT1/eNOS signaling, oxidative stress, cardiomyocyte remodeling
Zhu et al. (Mon,) conducted a other in Atrial Fibrillation (n=16). CRIF1 overexpression vs. Empty vector / Control was evaluated on Atrial fibrillation inducibility, duration, and cardiomyocyte remodeling markers (p=<0.001). CRIF1 overexpression significantly attenuated Angiotensin II-induced atrial fibrillation susceptibility, cardiomyocyte apoptosis, and hypertrophy by activating the SIRT1/eNOS signaling pathway.