PMID- 12555143
OWN - NLM
STAT- MEDLINE
DCOM- 20030408
LR  - 20061115
IS  - 1071-9164 (Print)
IS  - 1071-9164 (Linking)
VI  - 8
IP  - 6 Suppl
DP  - 2002 Dec
TI  - Integration of concepts: cardiac extracellular matrix remodeling after myocardial 
      infarction.
PG  - S344-8
AB  - The cardiac extracellular matrix consists of a three-dimensional structural 
      network of interstitial collagens to which other matrix components are attached. 
      The main physiological functions of this network are to retain tissue integrity 
      and cardiac pump function. Collagen deposition is controlled and can be modulated 
      by hormonal factors, growth factors, cytokines, regulatory proteins and/or 
      hemodynamic factors. Increased collagen deposition is a prerequisite to prevent 
      dilatation of the infarcted area. Excessive accumulation of collagen leads to 
      ventricular diastolic and systolic dysfunction and ultimately contributes to 
      heart failure. An appropriate balance of extracellular matrix synthesis and 
      degradation is required for normal morphogenesis and maintenance of tissue 
      architecture. A disbalance in the extracellular matrix turnover either by 
      decreased matrix synthesis and/or increased degradation leads to less than normal 
      extracellular matrix in the myocardium which in its turn may lead to cardiac 
      dilatation or even rupture. Extracellular matrix degrading enzymes expressed 
      after myocardial infarction belong to the families of serine and matrix 
      metalloproteinases (MMPs) and are secreted as latent proenzymes that have to be 
      activated. It is crucial to keep the activity of these enzymes under tight 
      control by either influencing the synthesis, activation or inhibition by tissue 
      inhibitors of MMPs (TIMPs) or alpha2-macroglobulin. First studies using MMP 
      inhibitors in experimental models of myocardial infarction seem to give 
      attenuation of ventricular geometry but not always improvement of cardiac 
      function. A central role in the activation of MMPs plays the plasminogen-plasmin 
      system. Invasion of inflammatory cells and hitherto the rest of the wound healing 
      cascade is inhibited in plasminogen or uPA deficient mice, most likely by the 
      inhibition of MMP activity. Regulating the balance of extracellular matrix 
      remodeling either by extracellular matrix synthesis or degradation might be one 
      of the possible prevention mechanisms for heart failure. But also regeneration of 
      the vascular and cardiomyocyte network might be potential new treatments for 
      people with heart failure.
FAU - Cleutjens, Jack P M
AU  - Cleutjens JP
AD  - Department of Pathology, Cardiovascular Research Institute Maastricht, University 
      Maastricht, Maastricht, The Netherlands.
FAU - Creemers, Esther E J M
AU  - Creemers EE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Card Fail
JT  - Journal of cardiac failure
JID - 9442138
RN  - 0 (Protease Inhibitors)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - 9007-34-5 (Collagen)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Animals
MH  - Collagen/physiology
MH  - Extracellular Matrix/*physiology
MH  - Humans
MH  - Matrix Metalloproteinases/*physiology
MH  - Mice
MH  - Myocardial Infarction/*physiopathology
MH  - Protease Inhibitors/pharmacology
MH  - Tissue Inhibitor of Metalloproteinases/pharmacology
MH  - *Ventricular Remodeling
EDAT- 2003/01/30 04:00
MHDA- 2003/04/09 05:00
CRDT- 2003/01/30 04:00
PHST- 2003/01/30 04:00 [pubmed]
PHST- 2003/04/09 05:00 [medline]
PHST- 2003/01/30 04:00 [entrez]
AID - S1071916402004748 [pii]
AID - 10.1054/jcaf.2002.129261 [doi]
PST - ppublish
SO  - J Card Fail. 2002 Dec;8(6 Suppl):S344-8. doi: 10.1054/jcaf.2002.129261.