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


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.
Wilson
Eric M
EM
Medical University of South Carolina, Charleston, SC 29425, USA.
Moainie
Sina L
SL
Baskin
Julia M
JM
Lowry
Abigail S
AS
Deschamps
Anne M
AM
Mukherjee
Rupak
R
Guy
T Sloane
TS
St John-Sutton
Martin G
MG
Gorman
Joseph H
JH
Edmunds
L Henry
LH
Gorman
Robert C
RC
Spinale
Francis G
FG
D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D004790:Enzyme Induction / Q000502:physiology; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000503:physiopathology; D020782:Matrix Metalloproteinases / Q000096:biosynthesis*; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000201:enzymology / Q000503:physiopathology*; D012756:Sheep; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D014463:Ultrasonography / Q000295:instrumentation / Q000379:methods; D020257:Ventricular Remodeling / Q000502:physiology
D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases