PMID- 16829192
OWN - NLM
STAT- MEDLINE
DCOM- 20070130
LR  - 20220408
IS  - 1388-9842 (Print)
IS  - 1388-9842 (Linking)
VI  - 8
IP  - 7
DP  - 2006 Nov
TI  - Toll-like receptor 4 modulates myocardial ischaemia-reperfusion injury: Role of 
      matrix metalloproteinases.
PG  - 665-72
AB  - Toll-like receptor 4 (TLR4) mediates innate immune responses following 
      endotoxemia and myocardial ischaemia-reperfusion (I/R) injury. Pre-treatment with 
      the major TLR4 ligand lipopolysaccharide (LPS) reduces infarct size. Matrix 
      metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) play a crucial 
      role in endotoxemia possibly also determining I/R injury. AIMS: We investigated 
      the influence of TLR4 on infarct size and assessed the influence of MMP and TIMP 
      regulation on I/R injury. METHODS: Left anterior descending artery (LAD) 
      occlusion was performed on wild-type (C3H/HeN) and TLR4-deficient (C3H/HeJ) mice. 
      Animals were stimulated with LPS (1 mg/kg) or PBS 16 h ahead of 60 min LAD 
      ligation. After 24 h of reperfusion, triphenyltetrazolium chloride staining was 
      performed and infarct size was measured by planimetry. MMP- and TIMP-mRNA 
      expression were determined by RPA after 3 h of reperfusion. MMP zymographic 
      activity was monitored 6 h after occlusion. RESULTS: TLR4-deficient mice and 
      LPS-treated wild-type mice showed significantly reduced infarct areas. 
      LPS-stimulation significantly increased the overall MMP/TIMP mRNA expression 
      ratio due to elevated MMP-3, -8, -9, and TIMP-1 in wild-type mice. I/R overall 
      reduced the MMP/TIMP ratio due to increased MMP-1, TIMP-1, and -3 mRNA 
      expression. CONCLUSIONS: LPS pre-treatment and TLR4-deficiency led to a decreased 
      infarct size. However, infarct area and MMP/TIMP ratio were not correlated. This 
      means that in TLR4-deficient mice MMP/TIMP ratios are not determining the infarct 
      size.
FAU - Stapel, Heidi
AU  - Stapel H
AD  - Institute of Physiology II, University of Bonn, Germany.
FAU - Kim, Se-Chan
AU  - Kim SC
FAU - Osterkamp, Steffen
AU  - Osterkamp S
FAU - Knuefermann, Pascal
AU  - Knuefermann P
FAU - Hoeft, Andreas
AU  - Hoeft A
FAU - Meyer, Rainer
AU  - Meyer R
FAU - Grohe, Christian
AU  - Grohe C
FAU - Baumgarten, Georg
AU  - Baumgarten G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060707
PL  - England
TA  - Eur J Heart Fail
JT  - European journal of heart failure
JID - 100887595
RN  - 0 (Lipopolysaccharides)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - 0 (Toll-Like Receptor 4)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Animals
MH  - Lipopolysaccharides/pharmacology
MH  - Male
MH  - Matrix Metalloproteinases/*metabolism
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Myocardial Infarction/*pathology
MH  - Myocardial Reperfusion Injury/*metabolism
MH  - RNA, Messenger/metabolism
MH  - Tissue Inhibitor of Metalloproteinases/metabolism
MH  - Toll-Like Receptor 4/*metabolism
EDAT- 2006/07/11 09:00
MHDA- 2007/01/31 09:00
CRDT- 2006/07/11 09:00
PHST- 2005/06/22 00:00 [received]
PHST- 2005/12/16 00:00 [revised]
PHST- 2006/03/16 00:00 [accepted]
PHST- 2006/07/11 09:00 [pubmed]
PHST- 2007/01/31 09:00 [medline]
PHST- 2006/07/11 09:00 [entrez]
AID - S1388-9842(06)00071-7 [pii]
AID - 10.1016/j.ejheart.2006.03.005 [doi]
PST - ppublish
SO  - Eur J Heart Fail. 2006 Nov;8(7):665-72. doi: 10.1016/j.ejheart.2006.03.005. Epub 
      2006 Jul 7.