| S100A8/A9 aggravates post-ischemic heart failure through activation of RAGE-dependent NF-κB signaling. | |
| | |
MedLine Citation:
|
PMID: 22318783 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
|
The extracellular heterodimeric protein S100A8/A9 activates the innate immune system through activation of the receptor of advanced glycation end products (RAGE) and Toll-like receptors. As activation of RAGE has recently been associated with sustained myocardial inflammation and heart failure (HF) we studied the role of S100A8/A9 in the development of post-ischemic HF. Hypoxia led to sustained induction of S100A8/A9 accompanied by increased nuclear factor (NF-)κB binding activity and increased expression of pro-inflammatory cytokines in cardiac fibroblasts and macrophages. Knockdown of either S100A8/A9 or RAGE rescued the induction of pro-inflammatory cytokines and NF-κB activation after hypoxia. In a murine model of post-ischemic HF both cardiac RNA and protein levels of S100A8/A9 were elevated as soon as 30 min after hypoxia with sustained activation up to 28 days after ischemic injury. Treatment with recombinant S100A8/A9 resulted in reduced cardiac performance following ischemia/reperfusion. Chimera experiments after bone marrow transplantation demonstrated the importance of RAGE expression on immune cells for their recruitment to the injured myocardium aggravating post-ischemic heart failure. Signaling studies in isolated ventricles indicated that MAP kinases JNK, ERK1/2 as well as NF-κB mediate signals downstream of S100A8/A9-RAGE in post-ischemic heart failure. Interestingly, cardiac performance was not affected by administration of S100A8/A9 in RAGE(-/-)-mice, which demonstrated significantly improved cardiac recovery compared to WT-mice. Our study provides evidence that sustained activation of S100A8/A9 critically contributes to the development of post-ischemic HF driving the progressive course of HF through activation of RAGE. |
| | |
Authors:
|
H Christian Volz; Danai Laohachewin; Cathrin Seidel; Felix Lasitschka; Kirsten Keilbach; Alexandra R Wienbrandt; Joachim Andrassy; Angelika Bierhaus; Ziya Kaya; Hugo A Katus; Martin Andrassy |
Related Documents
:
|
12566993 - Activation of th1 immunity is a common immune mechanism for the successful treatment of... 22304503 - Glutathione redox control of asthma: from molecular mechanisms to therapeutic opportuni... 20684053 - Otosclerosis: disturbed balance between cell survival and apoptosis. |
Publication Detail:
|
Type: Journal Article Date: 2012-02-10 |
Journal Detail:
|
Title: Basic research in cardiology Volume: 107 ISSN: 1435-1803 ISO Abbreviation: Basic Res. Cardiol. Publication Date: 2012 Mar |
Date Detail:
|
Created Date: 2012-02-09 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0360342 Medline TA: Basic Res Cardiol Country: Germany |
Other Details:
|
Languages: eng Pagination: 1-16 Citation Subset: IM |
Affiliation:
|
Department of Medicine III, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany. |
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: A phase I trial of S-1 with concurrent radiotherapy in patients with locally recurrent rectal cancer...
Next Document: Energy expenditure in obstructive sleep apnea: validation of a multiple physiological sensor for det...