Document Detail

Inhibition of plasminogen activators or matrix metalloproteinases prevents cardiac rupture but impairs therapeutic angiogenesis and causes cardiac failure.
MedLine Citation:
PMID:  10502816     Owner:  NLM     Status:  MEDLINE    
Cardiac rupture is a fatal complication of acute myocardial infarction lacking treatment. Here, acute myocardial infarction resulted in rupture in wild-type mice and in mice lacking tissue-type plasminogen activator, urokinase receptor, matrix metalloproteinase stromelysin-1 or metalloelastase. Instead, deficiency of urokinase-type plasminogen activator (u-PA-/-) completely protected against rupture, whereas lack of gelatinase-B partially protected against rupture. However, u-PA-/- mice showed impaired scar formation and infarct revascularization, even after treatment with vascular endothelial growth factor, and died of cardiac failure due to depressed contractility, arrhythmias and ischemia. Temporary administration of PA inhibitor-1 or the matrix metalloproteinase-inhibitor TIMP-1 completely protected wild-type mice against rupture but did not abort infarct healing, thus constituting a new approach to prevent cardiac rupture after acute myocardial infarction.
S Heymans; A Luttun; D Nuyens; G Theilmeier; E Creemers; L Moons; G D Dyspersin; J P Cleutjens; M Shipley; A Angellilo; M Levi; O Nübe; A Baker; E Keshet; F Lupu; J M Herbert; J F Smits; S D Shapiro; M Baes; M Borgers; D Collen; M J Daemen; P Carmeliet
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nature medicine     Volume:  5     ISSN:  1078-8956     ISO Abbreviation:  Nat. Med.     Publication Date:  1999 Oct 
Date Detail:
Created Date:  1999-10-21     Completed Date:  1999-10-21     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9502015     Medline TA:  Nat Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1135-42     Citation Subset:  IM    
Center for Transgene Technology, Flanders Interuniversity, Leuven, Belgium.
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MeSH Terms
Arrhythmias, Cardiac
Bone Marrow Transplantation
Cardiac Output, Low / etiology*
Cell Movement
Collagenases / metabolism
Gene Transfer Techniques
Heart Rupture / etiology*
Leukocytes / cytology,  metabolism
Matrix Metalloproteinase 3 / genetics
Matrix Metalloproteinase 9
Metalloendopeptidases / antagonists & inhibitors*
Mice, Mutant Strains
Myocardial Infarction / complications*,  drug therapy*
Neovascularization, Physiologic / drug effects
Plasminogen Activator Inhibitor 1 / genetics,  metabolism
Plasminogen Activators / genetics
Plasminogen Inactivators / therapeutic use*
Protease Inhibitors / therapeutic use*
Tissue Inhibitor of Metalloproteinase-1 / genetics,  metabolism
Reg. No./Substance:
0/Plasminogen Activator Inhibitor 1; 0/Plasminogen Inactivators; 0/Protease Inhibitors; 0/Tissue Inhibitor of Metalloproteinase-1; EC 3.4.21.-/Plasminogen Activators; EC 3.4.24.-/Collagenases; EC 3.4.24.-/Metalloendopeptidases; EC Metalloproteinase 3; EC Metalloproteinase 9
Comment In:
Nat Med. 1999 Oct;5(10):1122-3   [PMID:  10502807 ]

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