Telmisartan Reduces Atrial Fibrillation Susceptibility in Pressure Overload Rats and Its Molecular Mechanism Based on Gene Sequencing

Abstract

Background To assess the effects of telmisartan on susceptibility of atrial fibrillation (AF) in pressure overload rats, and to probe the underlying molecular mechanism and signal pathways. Methods Forty-nine 12-week-old male SD rats were randomly divided into sham operation (n = 15), abdominal aorta coarctation (AAC, n = 17), and AAC with telmisartan treatment groups (n = 17). Telmisartan 10 mg/(kg d) was administered by gavage for 4 weeks after AAC. Four weeks after operation, the indexes of echocardiography, hemodynamics, and cardiac electrophysiology including left atrial conduction time (LACT) and interatrial conduction time (IACT) were assessed. The mRNAs were extracted from left atrial tissues and analyzed by next generation sequencing. Results Systolic left ventricular pressure, systolic aortic pressure, left atrial diameters, and interventricular septal thickness in AAC rats were higher than those in sham rats (all P < 0.05), all of which were lowered by telmisartan treatment (all P < 0.05). LACT and IACT were significantly increased in AAC rats and ameliorated by telmisartan treatment. In isolated perfused heart, duration of AF induced by burst electrical stimulation was longer in AAC rats, which was shortened by telmisartan treatment. A total of 897 genes were downregulated by AAC but upregulated by telmisartan treatment (down/up 897 gene set). Also, 1,542 genes were upregulated by AAC but downregulated by telmisartan treatment (up/down 1,542 gene set). Venn and GO enrichment analyses showed that 5 target genes in the down/up 897 gene set were the key rate limiting enzymes of fatty acid oxidation while 5 target genes in the up/down 1,542 gene set were involved in Wnt/β-catenin signal pathway and type I and II collagen components. Conclusions Telmisartan lowers AF susceptibility via suppressing the left atrial enlargement and shortening atrial conduction time. Possible molecular mechanisms may be related to the improvement of fatty acid oxidation and downregulation of the Wnt/β-catenin pathway and collagen expression.