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Updated: May 8, 2026
Murine Myocardial Infarction Model using Permanent Ligation of Left Anterior Descending Coronary Artery
Published on: August 16, 2019
Establishment of a novel murine model of ischemic cardiomyopathy with multiple diffuse coronary lesions
Hajime Nakaoka1, Yumiko Nakagawa-Toyama, Makoto Nishida
1Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Insights
Researchers modified the HypoE mouse model to study cardiac remodeling in atherosclerotic coronary artery disease. This new model allows for longer survival, enabling detailed investigation of heart failure development after myocardial infarction.
Area of Science:
- Cardiovascular Research
- Animal Models of Disease
- Atherosclerosis and Ischemic Heart Disease
Background:
- Coronary artery atherosclerosis underlies myocardial infarction and ischemic cardiomyopathy.
- Current mouse models, like coronary ligation, require advanced techniques.
- Existing HypoE mice models die too early for cardiac remodeling studies.
Purpose of the Study:
- To modify the HypoE mouse model for studying ischemic cardiomyopathy and cardiac remodeling.
- To establish a convenient and effective murine model for atherosclerosis research.
Main Methods:
- Shortened the Paigen diet duration in HypoE mice to 7 or 10 days.
- Initiated dietary intervention at 8 weeks of age, allowing survival up to 8 weeks post-intervention.
- Utilized echocardiography, coronary angiography, and molecular analyses (mRNA expression) to assess cardiac function and remodeling.
Main Results:
- The modified HypoE mouse model survived myocardial infarction, with a median survival of 36 days.
- Fractional shortening significantly decreased post-dietary intervention, indicating impaired cardiac function.
- Coronary angiography revealed diffuse atherosclerotic lesions, and cardiac remodeling/fibrosis was confirmed through molecular markers.
Conclusions:
- Modified HypoE mice provide a viable model for studying ischemic cardiomyopathy with diffuse coronary lesions.
- This model is suitable for investigating cardiac remodeling in an atherogenic context.
- Offers a novel and practical alternative for cardiovascular research.
Objectives:
Atherosclerotic lesions of the coronary arteries are the pathological basis for myocardial infarction and ischemic cardiomyopathy. Progression of heart failure after myocardial infarction is associated with cardiac remodeling, which has been studied by means of coronary ligation in mice. However, this ligation model requires excellent techniques. Recently, a new murine model, HypoE mouse was reported to exhibit atherogenic Paigen diet-induced coronary atherosclerosis and myocardial infarction; however, the HypoE mice died too early to make possible investigation of cardiac remodeling. Therefore, we aimed to modify the HypoE mouse model to establish a novel model for ischemic cardiomyopathy caused by atherosclerotic lesions, which the ligation model does not exhibit.
Methods And Results:
In our study, the sustained Paigen diet for the HypoE mice was shortened to 7 or 10 days, allowing the mice to survive longer. The 7-day Paigen diet intervention starting when the mice were 8 weeks old was adequate to permit the mice to survive myocardial infarction. Our murine model, called the "modified HypoE mouse", was maintained until 8 weeks, with a median survival period of 36 days, after the dietary intervention (male, n = 222). Echocardiography demonstrated that the fractional shortening 2 weeks after the Paigen diet (n = 14) significantly decreased compared with that just before the Paigen diet (n = 6) (31.4±11.9% vs. 54.4±2.6%, respectively, P<0.01). Coronary angiography revealed multiple diffuse lesions. Cardiac remodeling and fibrosis were identified by serial analyses of cardiac morphological features and mRNA expression levels in tissue factors such as MMP-2, MMP-9, TIMP-1, collagen-1, and TGF-β.
Conclusion:
Modified HypoE mice are a suitable model for ischemic cardiomyopathy with multiple diffuse lesions and may be considered as a novel and convenient model for investigations of cardiac remodeling on a highly atherogenic background.
