Document Detail


Identification of cardiac myosin-binding protein C as a candidate biomarker of myocardial infarction by proteomics analysis.
MedLine Citation:
PMID:  19721077     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Acute myocardial infarction (AMI) is a common cause of death for which effective treatments are available provided that diagnosis is rapid. The current diagnostic gold standards are circulating cardiac troponins I and T. However, their slow release delays diagnosis, and their persistence limits their utility in the identification of reinfarction. The aim was to identify candidate biomarkers of AMI. Isolated mouse hearts were perfused with oxygenated protein-free buffer, and coronary effluent was collected after ischemia or during matched normoxic perfusion. Effluents were analyzed using proteomics approaches based on one- or two-dimensional initial separation. Of the 459 proteins identified after ischemia with one-dimensional separation, 320 were not detected in the control coronary effluent. Among these were all classic existing biomarkers of AMI. We also identified the cardiac isoform of myosin-binding protein C in its full-length form and as a 40-kDa degradation product. This protein was not detected in the other murine organs examined, increased markedly with even trivial myocardial infarction, and could be detected in the plasma after myocardial infarction in vivo, a profile compatible with a biomarker of AMI. Two-dimensional fluorescence DIGE of ischemic and control coronary effluents identified more than 200 asymmetric spots verified by swapping dyes. Once again existing biomarkers of injury were confirmed as well as posttranslational modifications of antioxidant proteins such as peroxiredoxins. Perfusing hearts with protein-free buffers provides a platform of graded ischemic injury that allows detailed analysis of protein release and identification of candidate cardiac biomarkers like myosin-binding protein C.
Authors:
Sebastien Jacquet; Xiaoke Yin; Pierre Sicard; James Clark; Gajen S Kanaganayagam; Manuel Mayr; Michael S Marber
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-08-31
Journal Detail:
Title:  Molecular & cellular proteomics : MCP     Volume:  8     ISSN:  1535-9484     ISO Abbreviation:  Mol. Cell Proteomics     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-12-07     Completed Date:  2010-02-22     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  101125647     Medline TA:  Mol Cell Proteomics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2687-99     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Biological Markers / metabolism
Carrier Proteins / metabolism*
Chromatography, Liquid
Coronary Circulation
Electrophoresis, Gel, Two-Dimensional
Immunoblotting
Male
Mass Spectrometry
Mice
Mice, Inbred C57BL
Myocardial Infarction / metabolism*,  physiopathology
Myocardium / metabolism*,  pathology*
Oxidative Stress
Perfusion
Proteomics / methods*
Reproducibility of Results
Grant Support
ID/Acronym/Agency:
FS/08/002/24537//British Heart Foundation; //Department of Health
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Carrier Proteins; 0/myosin-binding protein C
Comments/Corrections

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