Soluble guanylate cyclase: restoration of the NO–sGC–cGMP signaling pathway activity. A new opportunity in the treatment of heart failure

Abstract

Studying the key mechanisms of cardiovascular diseases has opened new possibilities for the pharmacological impact on the pathophysiological mechanisms of heart failure (HF). The signaling pathway, nitric oxide – soluble guanylate cyclase – cyclic guanosine monophosphate (NJ-sGC-cGMP), provides normal functioning of the cardiovascular system in healthy people and serves as a potential target for medicines in HF with reduced ejection fraction (HFrEF). In HFrEF progression, the sGC activity decreases due to endothelial dysfunction and oxidative stress. The increased synthesis of cGMP resulting from sGC stimulation can restrict myocardial fibrosis, reduce stiffness of the vascular wall and induce vasodilation; in this process, the mechanism of action of sGC stimulators does not overlap with other therapeutic targets. According to the results of the international randomized clinical study VICTORIA, the use of the sGC stimulator, vericiguat, in patients with HF, ejection fraction <45%, and a recent episode of decompensation in their history reduced the risk of repeated hospitalization and cardiovascular death. Also, this treatment was characterized by a favorable safety profile when added to standard therapy.