Transverse aortic constriction in mice induced atrial fibrillation in 67% of animals versus 0% in sham controls (p < 0.05), with ECG and echocardiographic changes consistent with AF and cardiac remodeling.
Bioinformatics and cross-species analysis identified AKT1 and HSPA5 as key genes potentially linking autophagy and metabolic reprogramming to atrial fibrillation pathogenesis.
Effect estimate: AF inducibility rate 67% in TAC mice vs 0% in sham controls
Absolute Event Rate: 66.7% vs 0%
p-value: p=<0.05
Atrial fibrillation (AF) is the most common cardiac arrhythmia, and both metabolic reprogramming and autophagy have been implicated in its pathogenesis. However, the expression pattern of autophagy-related genes during metabolic reprogramming in AF remains elusive. We aimed to characterize the expression profiles of autophagy- and metabolic reprogramming-related genes in atrial tissue to gain pathophysiological insights into AF. Three datasets obtained from the Gene Expression Omnibus (GSE2240, GSE79768, and GSE14975) that included atrial tissue samples from patients with or without AF were subjected to a bioinformatics analysis, which identified 2812 differentially expressed genes. Eight autophagy- and metabolic reprogramming-related differentially expressed genes (A&MRRDEGs) were identified as key candidates through least absolute shrinkage and selection operator regression combined with the random forest approach. Meanwhile, mice underwent transverse aortic constriction (TAC) for 2 weeks in an AF model, and gene expression in atrial tissue was analyzed. In atrial tissues from TAC mice, only Akt1 and Hspa5 of the eight A&MRRDEGs exhibited expression changes concordant with the human datasets, while Glud1 showed discordant regulation. Collectively, these cross-species findings highlight that the eight A&MRRDEGs, particularly AKT1 and HSPA5, are potentially involved in autophagy and metabolic reprogramming during AF pathogenesis.
Niu et al. (Sun,) conducted a other in Adults with non-valvular atrial fibrillation and sinus rhythm controls providing atrial tissue samples for transcriptomic analysis (n=66). Transverse aortic constriction (TAC) procedure in C57BL/6jjcl male mice vs. Sham surgery was evaluated on Incidence of inducible atrial fibrillation (AF) confirmed by transesophageal electrical stimulation, ECG parameters, and echocardiographic measurements (AF inducibility rate 67% in TAC mice vs 0% in sham controls, p=<0.05). Transverse aortic constriction in mice induced atrial fibrillation in 67% of animals versus 0% in sham controls (p < 0.05), with ECG and echocardiographic changes consistent with AF and cardiac remodeling.