Prevention of PKG-1{alpha} Oxidation Suppresses Antihypertrophic/Antifibrotic Effects From PDE5 Inhibition but not sGC Stimulation [Original Articles]

Conclusions:
In the stressed heart and myocytes, PKG1α C42-disulfide formation contributes to PDE5 activation. This augments the pathological role of PDE5 and so in turn enhances the therapeutic impact from its inhibition. PKG1α oxidation does not change the benefits from sGC activation. This finding favors the use of sGC activators regardless of PKG1α oxidation and may help guide precision therapy leveraging the cyclic GMP/PKG pathway to treat heart disease.

Source: Circulation: Heart Failure - March 15, 2018 Category: Cardiology Authors: Nakamura, T., Zhu, G., Ranek, M. J., Kokkonen-Simon, K., Zhang, M., Kim, G. E., Tsujita, K., Kass, D. A. Tags: Myocardial Biology, Oxidant Stress, Heart Failure, Hypertrophy, Pharmacology Original Articles Source Type: research