Document Detail

Imbalance between tissue inhibitor of metalloproteinase-4 and matrix metalloproteinases during acute myocardial [correction of myoctardial] ischemia-reperfusion injury.
MedLine Citation:
PMID:  12707244     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: We have previously reported that matrix metalloproteinase-2 (MMP-2) contributes to myocardial ischemia-reperfusion injury by degradation of troponin I, a regulatory element of the contractile proteins. MMP activities are also tightly regulated by tissue inhibitors of metalloproteinase (TIMPs). The change in TIMPs during acute myocardial ischemia-reperfusion injury is not clear. METHODS AND RESULTS: Isolated rat hearts were perfused either aerobically for 75 minutes or subjected to 15, 20, or 25 minutes of global, no-flow ischemia followed by 30 minutes of aerobic reperfusion. During reperfusion after ischemia, there was a rapid, enhanced release of TIMP-4, the most abundant TIMP in the heart, into the coronary effluent, as shown both by reverse zymography and Western blot. There was a negative correlation between the recovery of cardiac mechanical function and the release of TIMP-4 during reperfusion in hearts subjected to different durations of ischemia. Immunogold electron microscopy revealed a close association of TIMP-4 with the sarcomeres in aerobically perfused hearts. Moreover, TIMP-4 was present only in thin myofilaments prepared from aerobically perfused hearts but not in ischemic-reperfused hearts. An enhanced MMP activity was shown in ischemic-reperfused hearts by in situ zymography. CONCLUSIONS: Loss of TIMP-4 from the cardiac myocyte leads to an increase in net myocardial MMP activity that contributes to acute myocardial stunning injury.
Costas J Schulze; Wenjie Wang; Wilma L Suarez-Pinzon; Jolanta Sawicka; Grzegorz Sawicki; Richard Schulz
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2003-04-21
Journal Detail:
Title:  Circulation     Volume:  107     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2003 May 
Date Detail:
Created Date:  2003-05-20     Completed Date:  2003-05-23     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2487-92     Citation Subset:  AIM; IM    
Department of Pharmacology, University of Alberta, Edmonton, Alberta, T6G 2S2 Canada.
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MeSH Terms
Acute Disease
Enzyme Activation
Matrix Metalloproteinases / metabolism*
Microfilaments / metabolism,  ultrastructure
Myocardial Ischemia / metabolism*
Myocardial Reperfusion
Myocardium / metabolism*,  ultrastructure
Rats, Sprague-Dawley
Recovery of Function
Reperfusion Injury / metabolism*
Sarcomeres / metabolism,  ultrastructure
Time Factors
Tissue Inhibitor of Metalloproteinases / metabolism*
Reg. No./Substance:
0/Tissue Inhibitor of Metalloproteinases; 0/tissue inhibitor of metalloproteinase-4; EC 3.4.24.-/Matrix Metalloproteinases

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

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