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Updated: Jul 22, 2026
Coronary Artery Ligation and Intramyocardial Injection in a Murine Model of Infarction
Published on: June 7, 2011
Myocardial infarct expansion and matrix metalloproteinase inhibition
Rupak Mukherjee1, Theresa A Brinsa, Kathryn B Dowdy
1Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, SC 29425, USA.
Background:
A potential mechanism for left ventricular (LV) remodeling after myocardial infarction (MI) is activation of the matrix metalloproteinases (MMPs). This study examined the effects of MMP inhibition (MMPi) on regional LV geometry and MMP levels after MI.
Methods And Results:
In pigs instrumented with radiopaque markers to measure regional myocardial geometry, MI was created by ligating the obtuse marginals of the circumflex artery. In the first study, pigs were randomized to MMPi (n=7; PD166793, 20 mg x kg(-1) x d(-1)) or MI only (n=7) at 5 days after MI, and measurements were performed at 2 weeks. Regional MI areas were equivalent at randomization and were increased in the MI-only group at 2 weeks after MI compared with the MMPi group. In the second study, pigs randomized to MMPi (n=9) or MI only (n=8) were serially followed up for 8 weeks. At 8 weeks after MI, LV end-diastolic dimension was lower with MMPi than in the MI-only group (4.7+/-0.1 versus 5.1+/-0.1 cm, P<0.05). Regional MI area was reduced with MMPi at 8 weeks after MI (1.3+/-0.1 versus 1.7+/-0.1 cm2, P<0.05). MMPi reduced ex vivo MMP proteolytic activity. In the MI region, membrane-type MMP levels were normalized and levels of the endogenous tissue inhibitor of MMPs (TIMP-1) were increased compared with normal levels with MMPi. These effects were not observed in the MI-only group.
Conclusions:
MMPi attenuated the degree of post-MI LV dilation and expansion of the infarct during the late phase of MI healing. In addition, exogenous MMPi caused region-specific modulation of certain MMP and TIMP species.
Insights
Matrix metalloproteinase inhibition (MMPi) reduced left ventricular (LV) dilation and infarct expansion after myocardial infarction (MI). MMPi also modulated specific MMP and tissue inhibitor of MMPs (TIMP) levels in the affected heart region.
Area of Science:
- Cardiovascular Research
- Cardiac Remodeling
- Pharmacological Intervention
Background:
- Left ventricular (LV) remodeling post-myocardial infarction (MI) may involve matrix metalloproteinase (MMP) activation.
- Investigating MMP inhibition (MMPi) offers a potential therapeutic strategy.
Purpose of the Study:
- To evaluate the impact of MMP inhibition on regional LV geometry following myocardial infarction.
- To assess changes in MMP and tissue inhibitor of MMPs (TIMP) levels after MI with MMPi.
Main Methods:
- Utilized pigs with radiopaque markers to measure regional myocardial geometry after inducing MI.
- Administered MMPi (PD166793) or placebo to pigs post-MI and assessed outcomes over 2 and 8 weeks.
- Measured LV dimensions, infarct size, MMP activity, and TIMP-1 levels.
Main Results:
- MMPi significantly attenuated LV end-diastolic dimension and reduced regional infarct area at 8 weeks post-MI compared to the MI-only group.
- Ex vivo MMP proteolytic activity was reduced by MMPi.
- MMPi normalized membrane-type MMP levels and increased TIMP-1 levels in the MI region.
Conclusions:
- MMP inhibition effectively attenuated LV dilation and infarct expansion during the late phase of MI healing.
- Exogenous MMPi demonstrated region-specific modulation of MMPs and TIMPs.
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