Vericiguat reduces electrical and structural remodeling in a rabbit model of atrial fibrillation

Abstract

Purpose: The molecular etiology of atrial fibrillation (AF) and its treatment are poorly understood. AF involves both electrical and structural features. Vericiguat can ameliorate cardiac remodeling in heart failure. The effects of vericiguat on AF, however, are unclear. Here, the actions of vericiguat on atrial structural and electrical remodeling in AF and its possible mechanisms were investigated. Methods and Results: Thirty-six rabbits were randomly allocated to four groups, namely, sham, RAP (pacing with 600 beats/min over three weeks), vericiguat-treated (three weeks’ pacing plus daily oral dose of 1.5 mg/kg of vericiguat), and vericiguat-treated only. HL-1 cells received rapid pacing with or without vericiguat. Parameters including electrophysiology, echocardiography, histology, Ca2+ levels, and ICaL density, as well as levels of TRPC6, CaN, NFAT4, p-NFAT4, Cav1.2, collagen I, collagen III, and ST2 were measured. Significant changes of above proteins expression level, circulating biochemical indices, Ca2+ concentrations, and ICaL density in both animals and cell models, these effects were significantly restored by vericiguat. Vericiguat also reversed the enlarged atrium and significantly reduced myocardial fibrosis, together with preventing reduced atrial effective refractory periods (AERPs) and AF induction rate. Conclusion: Vericiguat thus ameliorated AF-associated structural and electrical remodeling. These findings suggest the potential of vericiguat for treating AF.

Upregulated Genes in Atrial Fibrillation Blood and the Left Atrium

“…Thicker lines indicate stronger correlations. consistent with those of previous studies that have shown that coagulation is increased in the blood of patients with AF [20,21] and that fibrosis is increased in the left atrium of patients with AF [22,23].…”

How does NFAT3 regulate the occurrence of cardiac hypertrophy?

“…The functions of NFAT2, NFAT4 and NFAT1 can overlap with NFAT3, but they might have distinct roles as well. NFAT1 and NFAT4 have been shown to regulate genes related to hypertrophic growth and fibrosis [94] , [95] . NFAT4, in particular, has been associated with the foetal gene program in the heart, which is reactivated during hypertrophy [32] .…”

Research on atrial fibrillation mechanisms and prediction of therapeutic prospects: focus on the autonomic nervous system upstream pathways

“…Vericiguat, a soluble guanylate cyclase agonist, has been investigated for its potential to treat AF by decreasing electrical and structural remodeling in rabbit models of AF. However, the specific mechanism of its effect on AF remains unclear, and the drug has not yet been widely validated, although it may hold potential value in AF treatment (101). Other studies have indicated that endoplasmic reticulum stress-induced autophagy is a crucial pathway in the progression of AF.…”