Does vericiguat attenuate Angiotensin II-induced oxidative stress and cardiac remodeling in preclinical models?
Vericiguat exerts cardioprotective, antihypertrophic, and antifibrotic effects by suppressing myocardial oxidative stress via regulation of ERK 1/2 or p38 MAPK signaling.
BACKGROUND: Vericiguat, an oral soluble guanylate cyclase stimulator, is a novel therapeutic agent for patients with heart failure with reduced ejection fraction; however, the detailed cardioprotective mechanism remains unclear. We aimed to explore the mechanism of the effect of vericiguat on the myocardium, particularly focusing on oxidative stress, using in vivo and in vitro experiments. METHODS AND RESULTS: production and cardiac hypertrophy-associated gene expression. In addition, AngII-induced phosphorylation of ERK 1/2 or p38 MAPK was significantly attenuated by the incubation with vericiguat. CONCLUSIONS: Our study demonstrated that vericiguat suppresses myocardial oxidative stress via the regulation of ERK 1/2 or p38 MAPK signaling, leading to antihypertrophic/fibrotic effects.
Harada et al. (Wed,) studied this question.