| Uncoupled eNOS annihilates neuregulin-1β-induced cardioprotection: a novel mechanism in pharmacological postconditioning in myocardial infarction. | |
| | |
MedLine Citation:
|
PMID: 23065382 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Myocardial infarct size can be limited by pharmacological postconditioning (pPC) with cardioprotective agents. Cardioprotective effects of neuregulin-1β (NRG) via activation of protein kinase B (Akt) and downstream pathways like endothelial nitric oxide synthase (eNOS) have been postulated based on results from cell culture experiments. The purpose of this study was to investigate if eNOS may be involved in pPC with NRG. NRG application in an ex vivo mouse model (C57Bl6) of ischemia-reperfusion injury was analyzed. Unexpectedly, the infarct size increased when NRG was infused starting 5 min prior to reperfusion, even though protective Akt and GSK3β phosphorylation were enhanced. In eNOS deficient mice, however, NRG significantly reduced the infarct size. Co-infusion of NRG and L-arginine (Arg) lead to a reduction in infarct size in wild type animals. Electron paramagnetic resonance measurements revealed that NRG treatment prior to reperfusion leads to an enhanced release of reactive oxygen species compared to controls and this effect is blunted by co-infusion of Arg. This study documents the cardioprotective mechanisms of NRG signaling to be mediated by GSK3β inactivation. This is the first study to show that this protection fails in situations with dysfunctional eNOS. In eNOS deficient mice NRG exerts its protective effect via the GSK3β pathway, suggesting that the eNOS can limit cardioprotection. As dysfunctional eNOS has been described in cardiovascular risk factors like diabetes, hypertension, and hypercholesterolemia these findings can help to explain lack of postconditioning performance in models of cardiovascular co-morbidities. |
| | |
Authors:
|
Bernd Ebner; Stefan A Lange; Thomas Eckert; Clementine Wischniowski; Annette Ebner; Rüdiger C Braun-Dullaeus; Christof Weinbrenner; Carsten Wunderlich; Gregor Simonis; Ruth H Strasser |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-10-12 |
Journal Detail:
|
Title: Molecular and cellular biochemistry Volume: - ISSN: 1573-4919 ISO Abbreviation: Mol. Cell. Biochem. Publication Date: 2012 Oct |
Date Detail:
|
Created Date: 2012-10-15 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0364456 Medline TA: Mol Cell Biochem Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Department of Medicine/Cardiology, Heart Center Dresden, University Hospital, University of Technology Dresden, Dresden, Germany, bernd_ebner@web.de. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Crocin, a dietary additive protects platelets from oxidative stress-induced apoptosis and inhibits p...
Next Document: Secretory Products from Epicardial Adipose Tissue of Patients with Type 2 Diabetes Induce Cardiomyoc...