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Murine Myocardial Infarction Model using Permanent Ligation of Left Anterior Descending Coronary Artery
Published on: August 16, 2019
Temporal changes in matrix metalloproteinase expression and inflammatory response associated with cardiac rupture
Zhen-Yin Tao1, Maria A Cavasin, Fang Yang
1Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202-2689, USA.
Abstract:
We previously found that male mice with myocardial infarction (MI) had a high rate of cardiac rupture, which generally occurred at 3 to 5 days after MI. Since matrix metalloproteinases (MMPs) play an important role in infarct healing, tissue repair and extracellular matrix (ECM) remodeling post-MI, we studied the temporal relationship of MMP expression and inflammatory response to cardiac rupture after acute MI. Male C57BL/6J mice were subjected to MI (induced by ligating the left anterior descending coronary artery) and killed 1, 2, 4, 7 or 14 days after MI. MMP-2 and MMP-9 activity in the heart were measured by zymography. Collagen content was measured by hydroxyproline assay. We found that after MI, MMP-9 activity increased as early as 1 day and reached a maximum by 2-4 days, associated with a similar increase in neutrophil and macrophage infiltration in the infarct area. MMP-2 started to increase rapidly within 4 days, reaching a maximum by 7 days and remaining high even at 14 days. Intense macrophage infiltration appeared by 4 days after MI and then gradually decreased within 7 to 14 days. Collagen content was unchanged until 4 days after MI, at which point it increased and remained high thereafter. Our data suggest that in mice, overexpression of MMP-2 and MMP-9 (possibly expressed mainly by neutrophils and macrophages) may lead to excessive ECM degradation in the early phase of MI, impairing infarct healing and aggravating early remodeling which in turn causes cardiac rupture.
Insights
Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, are linked to cardiac rupture after myocardial infarction (MI) in male mice. Their overexpression may impair healing and worsen remodeling, increasing rupture risk.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Cardiac Remodeling
Background:
- Myocardial infarction (MI) in male mice shows a high incidence of cardiac rupture 3-5 days post-event.
- Matrix metalloproteinases (MMPs) are crucial for post-MI infarct healing, tissue repair, and extracellular matrix (ECM) remodeling.
Purpose of the Study:
- To investigate the temporal correlation between matrix metalloproteinase (MMP) expression, inflammatory response, and cardiac rupture following acute myocardial infarction (MI).
Main Methods:
- Male C57BL/6J mice underwent MI induction via coronary artery ligation.
- Mice were euthanized at 1, 2, 4, 7, and 14 days post-MI.
- Heart tissue was analyzed for MMP-2 and MMP-9 activity (zymography), collagen content (hydroxyproline assay), and inflammatory cell infiltration (neutrophils and macrophages).
Main Results:
- MMP-9 activity peaked at 2-4 days post-MI, coinciding with increased neutrophil and macrophage infiltration.
- MMP-2 levels rose significantly by 4 days, peaking at 7 days and remaining elevated through 14 days.
- Collagen content increased from 4 days onwards, while macrophage infiltration peaked around day 4 and declined by days 7-14.
Conclusions:
- Elevated MMP-2 and MMP-9 expression, potentially from neutrophils and macrophages, in early MI phases may cause excessive ECM degradation.
- This degradation can impair infarct healing and exacerbate early cardiac remodeling, leading to increased cardiac rupture risk in male mice.
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