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Updated: Jul 13, 2026
Minimal Invasive Surgical Procedure of Inducing Myocardial Infarction in Mice
Published on: May 4, 2015
A novel dual staining method for identification of apoptotic cells reveals a modest apoptotic response in infarcted
Douglas J Taatjes1, Marilyn P Wadsworth, A K M Tarikuz Zaman
1Department of Pathology, College of Medicine, University of Vermont, 89 Beaumont Avenue, Burlington, VT 05405, USA. douglas.taatjes@uvm.edu
Abstract:
Confocal scanning laser microscopy was used to investigate the myocardium of control C57BL/6 and plasminogen activator inhibitor 1 knockout (PAI-1KO) mice 3 days following persistent ligation of the left descending coronary artery. Paraffin sections taken from infarcted areas of the left ventricle were stained with antibodies recognizing cardiomyocytes, neutrophils, macrophages and apoptotic cells. In both animal groups, a strong neutrophil response was noted in the infarcted myocardium, with a large proportion of these cells also displaying staining for anti-alpha-sarcomeric actin in the PAI-1KO animals. Abundant macrophages were also identified in the infarcted regions of both animal groups, forming demonstrable streams at the border region in the C57BL/6 control animals. Surprisingly, only sparse cells from both animal groups were labeled with the apoptotic markers anti-cleaved caspase 3 antibody and anti-single stranded DNA antibody (following formamide treatment). A dual immunostaining protocol was developed to localize both of these apoptotic markers in the same cell. Again, only scattered cells were found displaying both markers in the zones of infarction, suggesting that 3 days of persistent ischemia results in a robust necrotic response, but only a very minor apoptotic response in this mouse model.
Insights
This study investigated myocardial infarction in mice, finding a significant neutrophil and macrophage response but minimal apoptosis three days post-ischemia. Plasminogen activator inhibitor-1 knockout mice showed similar patterns, indicating necrosis dominates early infarction.
Area of Science:
- Cardiovascular Biology
- Immunology
- Cell Death Mechanisms
Background:
- Myocardial infarction (MI) involves complex inflammatory and cell death processes.
- The role of plasminogen activator inhibitor-1 (PAI-1) in post-MI cardiac remodeling is not fully understood.
- Distinguishing between necrosis and apoptosis is crucial for understanding infarct evolution.
Purpose of the Study:
- To compare the inflammatory and apoptotic responses in the myocardium of control and PAI-1 knockout mice following induced myocardial infarction.
- To investigate the extent of cardiomyocyte apoptosis versus necrosis in the early stages of infarction.
Main Methods:
- Confocal scanning laser microscopy was employed to examine myocardial tissue.
- Immunohistochemistry was used to identify cardiomyocytes, neutrophils, macrophages, and apoptotic cells.
- Dual immunostaining was performed to detect multiple apoptotic markers simultaneously.
Main Results:
- Both control and PAI-1 knockout mice exhibited robust neutrophil and macrophage infiltration into the infarcted myocardium.
- A significant portion of neutrophils in PAI-1 knockout mice stained positive for anti-alpha-sarcomeric actin.
- Apoptotic markers (cleaved caspase 3, single-stranded DNA) were detected in only sparse cells, suggesting a predominantly necrotic response.
Conclusions:
- Early myocardial infarction (3 days) in this mouse model is characterized by a strong inflammatory response and extensive necrosis.
- Apoptosis plays a minor role in the observed cell death within the infarct zone at this time point.
- PAI-1 deficiency did not significantly alter the inflammatory cell infiltration or the balance of necrosis versus apoptosis in the early infarct.
