Old dog, new tricks: novel cardiac targets and stress regulation by protein kinase G.

Abstract:

:The second messenger cyclic guanosine 3'5' monophosphate (cGMP) and its downstream effector protein kinase G (PKG) have been discovered more than 40 years ago. In vessels, PKG1 induces smooth muscle relaxation in response to nitric oxide signalling and thus lowers systemic and pulmonary blood pressure. In platelets, PKG1 stimulation by cGMP inhibits activation and aggregation, and in experimental models of heart failure (HF), PKG1 activation by inhibiting cGMP degradation is protective. The net effect of the above-mentioned signalling is cardiovascular protection. Yet, while modulation of cGMP-PKG has entered clinical practice for treating pulmonary hypertension or erectile dysfunction, translation of promising studies in experimental HF to clinical success has failed thus far. With the advent of new technologies, novel mechanisms of PKG regulation, including mechanosensing, redox regulation, protein quality control, and cGMP degradation, have been discovered. These novel, non-canonical roles of PKG1 may help understand why clinical translation has disappointed thus far. Addressing them appears to be a requisite for future, successful translation of experimental studies to the clinical arena.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Rainer PP,Kass DA

doi

10.1093/cvr/cvw107

subject

Has Abstract

pub_date

2016-07-15 00:00:00

pages

154-62

issue

2

eissn

0008-6363

issn

1755-3245

pii

cvw107

journal_volume

111

pub_type

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