Myocardial infarction does not accelerate atherosclerosis in a mouse model of type 1 diabetes

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 if diabetes and experimental myocardial infarction synergize to accelerate atherosclerosis, we performed ligation of the left anterior descending coronary artery to induce experimental MI or sham surgery in non-diabetic and diabetic mice with pre-existing atherosclerosis. All mice subjected to experimental MI had significantly reduced left ventricular function. In our model, neither diabetes nor MI resulted in monocytosis compared to non-diabetic sham mice. 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 because mice with myeloid cells deficient in the adhesion molecule alpha 4 integrin 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 the acceleration of the underlying pathology from a previous MI.