Figure 2.

The mechanism of vericiguat. Under normal conditions, NO is generated in endothelial cells and diffuses to neighboring tissues. NO enters vascular/cardiac muscle cells in the heart and stimulates the intracellular receptor sGC to generate cGMP. In HF, there is endothelial dysfunction due to oxidative stress and inflammation and ROS, and ROS reduce NO bioavailability, leading to insufficient activation of sGC. The resulting cGMP deficiency is associated with microvascular dysfunction, cardiomyocyte stiffness, and fibrosis, ultimately leading to myocardial dysfunction. Vericiguat can sensitize sGC and directly stimulate the enzyme to the limited amounts of endogenous NO. cGMP = cyclic guanosine monophosphate; NO = nitric oxide; ROS = reactive oxygen species; sGC = soluble guanylate cyclase. Created with BioRender.com.