PMID- 12771000
OWN - NLM
STAT- MEDLINE
DCOM- 20030625
LR  - 20161124
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 107
IP  - 22
DP  - 2003 Jun 10
TI  - Region- and type-specific induction of matrix metalloproteinases in 
      post-myocardial infarction remodeling.
PG  - 2857-63
AB  - BACKGROUND: Induction of matrix metalloproteinases (MMPs) contributes to adverse 
      remodeling after myocardial infarction (MI). Whether a region- and type-specific 
      distribution of MMPs occurs within the post-MI myocardium remained unknown. 
      METHODS AND RESULTS: Ten sheep were instrumented with a sonomicrometry array to 
      measure dimensions in 7 distinct regions corresponding to the remote, transition, 
      and MI regions. Eight sheep served as reference controls. The relative abundance 
      of representative MMP types and the tissue inhibitors of the MMPs (TIMPs) was 
      quantified by immunoblotting. Segment length increased from baseline in the 
      remote (24.9+/-5.4%), transition (18.0+/-2.9%), and MI (53.8+/-11.0%) regions at 
      8 weeks after MI (P<0.05) and was greatest in the MI region (P<0.05). Region- and 
      type-specific changes in MMPs occurred after MI. For example, MMP-1 and MMP-9 
      abundance was unchanged in the remote, fell to 3+/-2% in the transition, and was 
      undetectable in the MI region (P<0.05). MMP-13, MMP-8, and MT1-MMP increased by 
      >300% in the transition and MI regions (P<0.05). TIMP abundance decreased 
      significantly in the transition region after MI and fell to undetectable levels 
      within the MI region. CONCLUSIONS: The unique findings of this study were 2-fold. 
      First, changes in regional geometry after MI were associated with changes in MMP 
      levels. Second, a region-specific portfolio of MMPs was induced after MI and was 
      accompanied by a decline in TIMP levels, indicative of a loss of MMP inhibitory 
      control. Targeting the regional imbalance between specific MMPs and TIMPs within 
      the post-MI myocardium holds therapeutic potential.
FAU - Wilson, Eric M
AU  - Wilson EM
AD  - Medical University of South Carolina, Charleston, SC 29425, USA.
FAU - Moainie, Sina L
AU  - Moainie SL
FAU - Baskin, Julia M
AU  - Baskin JM
FAU - Lowry, Abigail S
AU  - Lowry AS
FAU - Deschamps, Anne M
AU  - Deschamps AM
FAU - Mukherjee, Rupak
AU  - Mukherjee R
FAU - Guy, T Sloane
AU  - Guy TS
FAU - St John-Sutton, Martin G
AU  - St John-Sutton MG
FAU - Gorman, Joseph H 3rd
AU  - Gorman JH 3rd
FAU - Edmunds, L Henry Jr
AU  - Edmunds LH Jr
FAU - Gorman, Robert C
AU  - Gorman RC
FAU - Spinale, Francis G
AU  - Spinale FG
LA  - eng
GR  - HL-59165/HL/NHLBI NIH HHS/United States
GR  - HL-63594/HL/NHLBI NIH HHS/United States
GR  - P01-HL-48788-08/HL/NHLBI NIH HHS/United States
GR  - R01 HL071137/HL/NHLBI NIH HHS/United States
GR  - HL-36308/HL/NHLBI NIH HHS/United States
GR  - R01 HL063954/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030527
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Animals
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Enzyme Induction/physiology
MH  - Heart Ventricles/diagnostic imaging/physiopathology
MH  - Matrix Metalloproteinases/*biosynthesis
MH  - Myocardial Infarction/diagnostic imaging/enzymology/*physiopathology
MH  - Sheep
MH  - Tissue Inhibitor of Metalloproteinases/metabolism
MH  - Ultrasonography/instrumentation/methods
MH  - *Ventricular Remodeling/physiology
EDAT- 2003/05/29 05:00
MHDA- 2003/06/26 05:00
CRDT- 2003/05/29 05:00
PHST- 2003/05/29 05:00 [pubmed]
PHST- 2003/06/26 05:00 [medline]
PHST- 2003/05/29 05:00 [entrez]
AID - 01.CIR.0000068375.40887.FA [pii]
AID - 10.1161/01.CIR.0000068375.40887.FA [doi]
PST - ppublish
SO  - Circulation. 2003 Jun 10;107(22):2857-63. doi: 
      10.1161/01.CIR.0000068375.40887.FA. Epub 2003 May 27.