AUTHOR=Numata Genri , Takimoto Eiki 

TITLE=Cyclic GMP and PKG Signaling in Heart Failure

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.792798

DOI=10.3389/fphar.2022.792798

ISSN=1663-9812

ABSTRACT=<p>Cyclic guanosine monophosphate (cGMP), produced by guanylate cyclase (GC), activates protein kinase G (PKG) and regulates cardiac remodeling. cGMP/PKG signal is activated by two intrinsic pathways: nitric oxide (NO)-soluble GC and natriuretic peptide (NP)-particulate GC (pGC) pathways. Activation of these pathways has emerged as a potent therapeutic strategy to treat patients with heart failure, given cGMP-PKG signaling is impaired in heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). Large scale clinical trials in patients with HFrEF have shown positive results with agents that activate cGMP-PKG pathways. In patients with HFpEF, however, benefits were observed only in a subgroup of patients. Further investigation for cGMP-PKG pathway is needed to develop better targeting strategies for HFpEF. This review outlines cGMP-PKG pathway and its modulation in heart failure.</p>