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Updated: Dec 14, 2025
Modeling and Evaluation of Murine Diabetic Cardiomyopathy Model
Published on: November 29, 2024
Myocardial Infarction Does Not Accelerate Atherosclerosis in a Mouse Model of Type 1 Diabetes
Farah Kramer1, Amy M Martinson2, Thalia Papayannopoulou3
1Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington Medicine Diabetes Institute, University of Washington School of Medicine, Seattle, WA.
Abstract:
In addition to increasing the risk of an initial myocardial infarction (MI), diabetes increases the risk of a recurrent MI. Previous work suggests that an experimental MI can accelerate atherosclerosis via monocytosis. To test whether diabetes and experimental MI synergize to accelerate atherosclerosis, we performed ligation of the left anterior descending coronary artery to induce experimental MI or sham surgery in nondiabetic and diabetic mice with preexisting atherosclerosis. All mice subjected to experimental MI had significantly reduced left ventricular function. In our model, in comparisons with nondiabetic sham mice, neither diabetes nor MI resulted in monocytosis. Neither diabetes nor MI led to increased atherosclerotic lesion size, but diabetes accelerated lesion progression, exemplified by necrotic core expansion. The necrotic core expansion was dependent on monocyte recruitment, as mice with myeloid cells deficient in the adhesion molecule integrin α4 were protected from necrotic core expansion. In summary, diabetes, but not MI, accelerates lesion progression, suggesting that the increased risk of recurrent MI in diabetes is due to a higher lesional burden and/or elevated risk factors rather than the acceleration of the underlying pathology from a previous MI.
Insights
Diabetes accelerates atherosclerosis progression, increasing recurrent myocardial infarction (MI) risk. However, experimental MI does not worsen atherosclerosis, suggesting diabetes, not prior MI, drives lesion burden.
Area of Science:
- Cardiovascular Disease Research
- Diabetes Complications
- Atherosclerosis Pathogenesis
Background:
- Diabetes mellitus significantly elevates the risk of both initial and recurrent myocardial infarction (MI).
- Prior research indicates that experimental MI may accelerate atherosclerosis through monocyte involvement.
- The synergistic effect of diabetes and experimental MI on atherosclerosis acceleration requires further investigation.
Purpose of the Study:
- To investigate whether diabetes and experimental myocardial infarction (MI) interact to accelerate atherosclerosis.
- To determine the impact of diabetes and MI on atherosclerotic lesion progression and characteristics.
- To elucidate the role of monocyte recruitment in diabetes-induced acceleration of atherosclerotic lesion expansion.
Main Methods:
- Induction of experimental myocardial infarction (MI) via left anterior descending coronary artery ligation or sham surgery in nondiabetic and diabetic mice with pre-existing atherosclerosis.
- Assessment of left ventricular function post-surgery.
- Quantification of atherosclerotic lesion size and characteristics, including necrotic core expansion.
- Evaluation of monocyte recruitment and the role of integrin α4 in myeloid cells.
Main Results:
- Experimental MI led to significantly reduced left ventricular function in all affected mice.
- Neither diabetes nor experimental MI alone caused increased atherosclerotic lesion size compared to nondiabetic sham mice.
- Diabetes, independently, accelerated atherosclerotic lesion progression, notably through necrotic core expansion.
- Necrotic core expansion was dependent on monocyte recruitment, as mice lacking myeloid integrin α4 were protected.
Conclusions:
- Diabetes accelerates atherosclerotic lesion progression, contributing to the increased risk of recurrent myocardial infarction (MI).
- Experimental MI in this model did not accelerate atherosclerosis, suggesting the underlying pathology is not directly worsened by a previous MI.
- The heightened risk of recurrent MI in diabetic patients likely stems from an increased lesional burden and/or other risk factors rather than accelerated atherosclerosis due to prior MI.
