Therapeutic Impact of Vericiguat on Ventricular Remodeling in a Pressure-Overload Heart Failure Model

Background: Pressure overload-induced heart failure is marked by pathological ventricular remodeling and myocardial fibrosis, contributing to impaired cardiac function and adverse clinical outcomes. Vericiguat, a soluble guanylate cyclase stimulator, has shown therapeutic promise in heart failure with reduced ejection fraction. However, its anti-fibrotic and metabolic effects in pressure overload models remain underexplored. Aim: This study aimed to investigate the anti-fibrotic and metabolic effects of Vericiguat in a murine model of pressure overload-induced cardiac remodeling. Material Method: Male mice (~25 g) underwent transverse aortic constriction (TAC) to induce pressure overload and received oral Vericiguat (10 mg/kg/day) for 14 days. Myocardial fibrosis was evaluated using Masson’s trichrome and Picrosirius red staining. Collagen deposition and wall stress indices were quantified. Proteomic profiling was performed on fibroblast- and myocyte-enriched cardiac tissue to identify differentially expressed proteins (DEPs) across metabolic, structural, mitochondrial, and signaling pathways. Results: Vericiguat treatment significantly reduced myocardial fibrosis and collagen accumulation compared to untreated TAC controls (p< 0.001). Improvements in wall stress indices were observed. Proteomic analysis revealed consistent modulation of DEPs, including reversal of TAC-induced downregulation of mitochondrial and energy-related proteins, indicating enhanced bioenergetic support. Conclusion: Vericiguat mitigates pressure overload-induced cardiac remodeling through anti-fibrotic and metabolic reprogramming mechanisms. These findings support its potential as a therapeutic strategy for heart failure and warrant further clinical investigation.