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Region- and type-specific induction of matrix metalloproteinases in post-myocardial infarction remodeling.

Publication ,  Journal Article
Wilson, EM; Moainie, SL; Baskin, JM; Lowry, AS; Deschamps, AM; Mukherjee, R; Guy, TS; St John-Sutton, MG; Gorman, JH; Edmunds, LH; Gorman, RC ...
Published in: Circulation
June 10, 2003

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.

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Published In

Circulation

DOI

EISSN

1524-4539

Publication Date

June 10, 2003

Volume

107

Issue

22

Start / End Page

2857 / 2863

Location

United States

Related Subject Headings

  • Ventricular Remodeling
  • Ultrasonography
  • Tissue Inhibitor of Metalloproteinases
  • Sheep
  • Myocardial Infarction
  • Matrix Metalloproteinases
  • Heart Ventricles
  • Enzyme Induction
  • Disease Progression
  • Disease Models, Animal
 

Citation

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Wilson, E. M., Moainie, S. L., Baskin, J. M., Lowry, A. S., Deschamps, A. M., Mukherjee, R., … Spinale, F. G. (2003). Region- and type-specific induction of matrix metalloproteinases in post-myocardial infarction remodeling. Circulation, 107(22), 2857–2863. https://doi.org/10.1161/01.CIR.0000068375.40887.FA
Wilson, Eric M., Sina L. Moainie, Julia M. Baskin, Abigail S. Lowry, Anne M. Deschamps, Rupak Mukherjee, T Sloane Guy, et al. “Region- and type-specific induction of matrix metalloproteinases in post-myocardial infarction remodeling.Circulation 107, no. 22 (June 10, 2003): 2857–63. https://doi.org/10.1161/01.CIR.0000068375.40887.FA.
Wilson EM, Moainie SL, Baskin JM, Lowry AS, Deschamps AM, Mukherjee R, et al. Region- and type-specific induction of matrix metalloproteinases in post-myocardial infarction remodeling. Circulation. 2003 Jun 10;107(22):2857–63.
Wilson, Eric M., et al. “Region- and type-specific induction of matrix metalloproteinases in post-myocardial infarction remodeling.Circulation, vol. 107, no. 22, June 2003, pp. 2857–63. Pubmed, doi:10.1161/01.CIR.0000068375.40887.FA.
Wilson EM, Moainie SL, Baskin JM, Lowry AS, Deschamps AM, Mukherjee R, Guy TS, St John-Sutton MG, Gorman JH, Edmunds LH, Gorman RC, Spinale FG. Region- and type-specific induction of matrix metalloproteinases in post-myocardial infarction remodeling. Circulation. 2003 Jun 10;107(22):2857–2863.

Published In

Circulation

DOI

EISSN

1524-4539

Publication Date

June 10, 2003

Volume

107

Issue

22

Start / End Page

2857 / 2863

Location

United States

Related Subject Headings

  • Ventricular Remodeling
  • Ultrasonography
  • Tissue Inhibitor of Metalloproteinases
  • Sheep
  • Myocardial Infarction
  • Matrix Metalloproteinases
  • Heart Ventricles
  • Enzyme Induction
  • Disease Progression
  • Disease Models, Animal