Document Detail

Proteomic analysis identifies in vivo candidate matrix metalloproteinase-9 substrates in the left ventricle post-myocardial infarction.
MedLine Citation:
PMID:  20354994     Owner:  NLM     Status:  MEDLINE    
Matrix metalloproteinase-9 (MMP-9) deletion has been shown to improve remodeling of the left ventricle post-myocardial infarction (MI), but the mechanisms to explain this improvement have not been fully elucidated. MMP-9 has a broad range of in vitro substrates, but relevant in vivo substrates are incompletely defined. Accordingly, we evaluated the infarct regions of wild-type (wt) and MMP-9 null (null) mice using a proteomic strategy. Wt and null groups showed similar infarct sizes (48+/-3 in wt and 45+/-3% in null), indicating that both groups received an equal injury stimulus. Left ventricle infarct tissue was homogenized and analyzed by 2-DE and MS. Of 31 spot intensity differences, the intensities of 9 spots were higher and 22 spots were lower in null mice compared to wt (all p<0.05). Several extracellular matrix proteins were identified in these spots by MS, including fibronectin, tenascin-C, thrombospondin-1, and laminin. Fibronectin was observed on the gels at a lower than expected molecular weight in the wt group, which suggested substrate cleavage, and the lower molecular weight spot was observed at lower intensity in the MMP-9 null group, which suggested cleavage by MMP-9. Immunoblotting confirmed the presence of fibronectin cleavage products in the wt samples and lower levels in the absence of MMP-9. In conclusion, examining infarct tissue from wt and MMP-9 null mice by proteomic analysis provides a powerful and unique method to identify in vivo candidate MMP substrates.
Rogelio Zamilpa; Elizabeth F Lopez; Ying Ann Chiao; Qiuxia Dai; Gladys P Escobar; Kevin Hakala; Susan T Weintraub; Merry L Lindsey
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Proteomics     Volume:  10     ISSN:  1615-9861     ISO Abbreviation:  Proteomics     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-06-07     Completed Date:  2010-09-07     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  101092707     Medline TA:  Proteomics     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  2214-23     Citation Subset:  IM    
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MeSH Terms
Electrophoresis, Gel, Two-Dimensional
Extracellular Matrix / metabolism*
Gene Expression Regulation / genetics,  physiology
Heart Ventricles / metabolism*,  pathology
Matrix Metalloproteinase 9 / genetics,  metabolism*
Mice, Inbred C57BL
Mice, Knockout
Myocardial Infarction / metabolism*,  physiopathology
Proteomics / methods*
Grant Support
Reg. No./Substance:
EC Metalloproteinase 9

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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