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Updated: Jul 14, 2026
Minimally Invasive Transverse Aortic Constriction in Mice
Published on: March 14, 2017
Matrix metalloproteinase inhibition attenuates early left ventricular enlargement after experimental myocardial
L E Rohde1, A Ducharme, L H Arroyo
1Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Background:
Extracellular matrix synthesis and degradation contribute to the morphological changes that occur after myocardial infarction (MI).
Methods And Results:
We tested the hypothesis that inhibition of matrix metalloproteinases (MMPs) attenuates left ventricular remodeling in experimental MI. Seventy-one male FVB mice that survived ligation of the left anterior coronary artery were randomized to a broad-spectrum MMP inhibitor (CP-471,474) or placebo by gavage. Echocardiographic studies were performed before randomization (within 24 hours of surgery) and 4 days later and included short-axis imaging at the midpapillary and apical levels. Infarction as defined by wall motion abnormality was achieved in 79% of the procedures (n=56), and mortality rate during the 4-day protocol was 23% (9 of 36 on treatment vs 7 of 35 on placebo; P=NS). Baseline end-diastolic and end-systolic dimensions and areas were similar (P=NS) between treated and placebo groups. At follow-up, infarcted mice allocated to MMP inhibitor had significantly smaller increases in end-systolic and end-diastolic dimensions and areas at both midpapillary and apical levels compared with infarcted mice allocated to placebo (all P<0.05). In addition, infarcted animals that received MMP inhibitor had no change in fractional shortening (-3+/-13%), whereas animals that received placebo had a decrease in fractional shortening (-12+/-12%) (P<0.05). In an analysis stratified by baseline end-diastolic area, the effects of MMP inhibition on the changes in end-systolic area and end-diastolic area were most prominent in animals that had more initial left ventricular dilatation (both P<0.05).
Conclusions:
-Administration of an MMP inhibitor attenuates early left ventricular dilation after experimental MI in mice. Further studies in genetically altered mice and other models will improve understanding of the role of MMPs in left ventricular remodeling.
Insights
Matrix metalloproteinase (MMP) inhibition reduced early left ventricular dilation after experimental myocardial infarction (MI) in mice. This suggests MMPs play a key role in post-MI cardiac remodeling.
Area of Science:
- Cardiovascular Research
- Cardiac Remodeling
- Pharmacology
Background:
- Extracellular matrix synthesis and degradation are critical in post-myocardial infarction (MI) morphological changes.
- Understanding these processes is key to developing treatments for cardiac remodeling.
Purpose of the Study:
- To investigate if inhibiting matrix metalloproteinases (MMPs) can reduce left ventricular (LV) remodeling following experimental MI.
- To test the hypothesis that MMP inhibition attenuates adverse LV changes after MI.
Main Methods:
- Seventy-one male mice underwent coronary artery ligation to induce MI.
- Survivors were randomized to a broad-spectrum MMP inhibitor (CP-471,474) or placebo.
- Echocardiography assessed LV dimensions and function before and 4 days after randomization.
Main Results:
- MMP inhibition significantly reduced increases in LV end-systolic and end-diastolic dimensions and areas.
- Mice treated with MMP inhibitors showed no decrease in fractional shortening, unlike placebo-treated mice.
- The beneficial effects of MMP inhibition were most pronounced in mice with greater initial LV dilation.
Conclusions:
- Administration of an MMP inhibitor attenuates early LV dilation after experimental MI in mice.
- Further research in genetically modified mice and other models is warranted to fully elucidate the role of MMPs in LV remodeling.
