Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Rainer, PP; Kass, DA.
Old dog, new tricks: novel cardiac targets and stress regulation by protein kinase G.
Cardiovasc Res. 2016; 111(2):154-162
Doi: 10.1093/cvr/cvw107
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- Führende Autor*innen der Med Uni Graz
- Rainer Peter
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- 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. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cardiovascular Agents - therapeutic use
- Cyclic GMP - metabolism
- Cyclic GMP-Dependent Protein Kinases - antagonists & inhibitors
- Cyclic GMP-Dependent Protein Kinases - metabolism
- Heart Diseases - drug therapy
- Heart Diseases - enzymology
- Heart Diseases - pathology
- Heart Diseases - physiopathology
- Humans -
- Molecular Targeted Therapy -
- Myocardium - enzymology
- Myocardium - pathology
- Oxidation-Reduction -
- Phosphodiesterase 5 Inhibitors - therapeutic use
- Proteasome Endopeptidase Complex - metabolism
- Protein Kinase Inhibitors - therapeutic use
- Signal Transduction -
- Stress, Physiological -
- TRPC Cation Channels - metabolism
- Find related publications in this database (Keywords)
- Protein kinase G
- cGMP-dependent protein kinase type 1
- Cardiac mechanosensing
- Proteasome
- Redox regulation
- Phosphodiesterase