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

• Published in: Circulation (New York, N.Y.) Vol. 107; no. 22; pp. 2857 - 2863
• Main Authors: WILSON, Eric M, MOAINIE, Sina L, GORMAN, Robert C, SPINALE, Francis G, BASKIN, Julia M, LOWRY, Abigail S, DESCHAMPS, Anne M, MUKHEJEE, Rupak, GUY, T. Sloane, ST JOHN-SUTTON, Martin G, GORMAN, Joseph H, EDMUNDS, L. Henry
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 10.06.2003; American Heart Association, Inc
• Subjects: Animals; Biological and medical sciences; Cardiology. Vascular system; Coronary heart disease; Disease Models, Animal; Disease Progression; Enzyme Induction - physiology; Heart; Heart Ventricles - diagnostic imaging; Heart Ventricles - physiopathology; Matrix Metalloproteinases - biosynthesis; Medical sciences; Myocardial Infarction - diagnostic imaging; Myocardial Infarction - enzymology; Myocardial Infarction - physiopathology; Sheep; Tissue Inhibitor of Metalloproteinases - metabolism; Ultrasonography - instrumentation; Ultrasonography - methods; Ventricular Remodeling - physiology; remodeling; Prognosis; Infarct; Enzyme; myocardial infarction; metalloproteinases; Cardiovascular disease; Metalloendopeptidases; Coronary heart disease; Myocardial disease; Gelatinase B; Gelatinase A; Vascular remodeling; Peptidases; Vertebrata; Mammalia; Animal; Neutrophil collagenase; Myocardium; Hydrolases; Sheep; Artiodactyla; Ungulata
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.0000068375.40887.FA

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. 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. 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.