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. 2022 Apr 11;13:792798. doi: 10.3389/fphar.2022.792798

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Copyright © 2022 Numata and Takimoto.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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cGMP/PKG signaling and PKG oxidation. Estrogen plays a pivotal role in cGMP-PKG signaling coupled with eNOS via estrogen receptor (ERɑ)-mediated non-nuclear signaling. In diseased conditions like heart failure, eNOS activity is impaired and PKG undertakes oxidation and localizes in cytosol, inhibiting protective effects of PKG signaling independent of cGMP and enhancing cardiac remodeling via target proteins like TRPC6. PDE5 inhibitor, sildenafil, reveals protective effects only under the condition of sufficient oxidated PKG1α, while sGC stimulator improves cardiac remodeling independent of PKG redox status.