PMID- 15937097
OWN - NLM
STAT- MEDLINE
DCOM- 20051121
LR  - 20200930
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 289
IP  - 5
DP  - 2005 Nov
TI  - Selective disruption of MMP-2 gene exacerbates myocardial inflammation and 
      dysfunction in mice with cytokine-induced cardiomyopathy.
PG  - H1858-64
AB  - Tumor necrosis factor-alpha (TNF-alpha) plays a pathophysiological role in the 
      development and progression of heart failure. Matrix metalloproteinase (MMP)-2 is 
      involved in extracellular matrix remodeling. Recent evidence suggests a 
      protective role for this protease against tissue inflammation. Although MMP-2 is 
      upregulated in the failing heart, little is known about its pathophysiological 
      role. We thus hypothesized that ablation of the MMP-2 gene could affect cardiac 
      remodeling and failure in TNF-alpha-induced cardiomyopathy. We crossed transgenic 
      mice with cardiac-specific overexpression of TNF-alpha (TG) with MMP-2 knockout 
      (KO) mice. Four groups of male and female mice were studied: wild-type (WT) with 
      wild MMP-2 (WT/MMP(+/+)), WT with MMP-2 KO (WT/MMP(-/-)), TNF-alpha TG with wild 
      MMP-2 (TG/MMP(+/+)), and TG with MMP-2 KO (TG/MMP(-/-)). The upregulation of 
      MMP-2 zymographic activity in TG/MMP(+/+) mice was completely abolished in 
      TG/MMP(-/-) mice, and other MMPs and tissue inhibitors of metalloproteinase were 
      comparable between groups. Survival was shorter for male TG/MMP(-/-) than 
      TG/MMP(+/+) mice. Female TG/MMP(-/-) mice were more severely affected than 
      TG/MMP(+/+) mice with diminished cardiac function. Myocardial TNF-alpha and other 
      proinflammatory cytokines were increased in TG/MMP(+/+) mice, and this increase 
      was similarly observed in TG/MMP(-/-) mice. The extent of myocardial infiltrating 
      cells including macrophages was greater in TG/MMP(-/-) than in TG/MMP(+/+) mice. 
      Selective ablation of the MMP-2 gene reduces survival and exacerbates cardiac 
      failure in association with the increased level of myocardial inflammation. MMP-2 
      may play a cardioprotective role in the pathogenesis of cytokine-induced 
      cardiomyopathy.
FAU - Matsusaka, Hidenori
AU  - Matsusaka H
AD  - Dept. of Cardiovascular Medicine, Kyushu Imoversotu Graduate School of Medical 
      Sciences, Fukuoka, Japan.
FAU - Ikeuchi, Masaki
AU  - Ikeuchi M
FAU - Matsushima, Shouji
AU  - Matsushima S
FAU - Ide, Tomomi
AU  - Ide T
FAU - Kubota, Toru
AU  - Kubota T
FAU - Feldman, Arthur M
AU  - Feldman AM
FAU - Takeshita, Akira
AU  - Takeshita A
FAU - Sunagawa, Kenji
AU  - Sunagawa K
FAU - Tsutsui, Hiroyuki
AU  - Tsutsui H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050603
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Cytokines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
SB  - IM
MH  - Animals
MH  - Cardiomyopathies/*chemically induced/*pathology/physiopathology
MH  - Cytokines/biosynthesis/genetics/*pharmacology
MH  - Electrocardiography
MH  - Female
MH  - Hemodynamics/physiology
MH  - Male
MH  - Matrix Metalloproteinase 2/*genetics
MH  - Mice
MH  - Mice, Knockout
MH  - Myocarditis/*pathology/physiopathology
MH  - Myocardium/pathology
MH  - Organ Size
MH  - RNA, Messenger/biosynthesis/genetics
MH  - Survival Analysis
MH  - Tissue Inhibitor of Metalloproteinases/physiology
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2005/06/07 09:00
MHDA- 2005/12/13 09:00
CRDT- 2005/06/07 09:00
PHST- 2005/06/07 09:00 [pubmed]
PHST- 2005/12/13 09:00 [medline]
PHST- 2005/06/07 09:00 [entrez]
AID - 00216.2005 [pii]
AID - 10.1152/ajpheart.00216.2005 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2005 Nov;289(5):H1858-64. doi: 
      10.1152/ajpheart.00216.2005. Epub 2005 Jun 3.