In addition to increasing the risk of an initial myocardial infarction (MI), diabetes increases the risk of a recurrent MI. Work by others suggests that an experimental MI can accelerate atherosclerosis via monocytosis. To test if diabetes and experimental myocardial infarction synergize to accelerate atherosclerosis, we induced atherosclerosis in Ldlr-/-; Gp+ mice, lethally irradiated them and transplanted with either wild type (WT) or LysM-Cre-mediated CD49D-deficient bone marrow. Following recovery, diabetes was induced using lymphocytic choriomeningitis virus, or saline was used as a control. The mice were subjected to ligation of the left anterior descending coronary artery to induce experimental MI or a sham surgery and then maintained for an additional 3 weeks. Diabetic (D) mice exhibited hyperglycemia and elevated plasma cholesterol and triglyceride levels compared to nondiabetic (ND) mice, but neither hematopoietic genotype or MI influenced that. All mice subjected to MI had significantly reduced left ventricular function. Neither diabetes nor MI resulted in monocytosis compared to ND sham mice. Despite not affecting total lesion size, the combination of diabetes and MI resulted in larger necrotic cores in the aortic sinus and in the brachiocephalic artery (9.8 ± 1% of total lesion in aortic sinus in ND sham, 11.9 ± 1% in ND MI, 15.4 ± 1% in D sham and 18.1 ± 2% in D MI, P<0.001 comparing ND Sham to D MI, n=14-24, ANOVA). The expansion of the necrotic cores was dependent on monocyte recruitment, since mice with myeloid cells deficient in the adhesion molecule CD49D were protected from necrotic core expansion. Diabetes and MI also synergized to accelerate macrophage cell death (6.1 ± 3% of peritoneal macrophages were dead in ND sham, 6.1 ± 3% in ND MI, 11± 1% in D sham and 20 ± 3% in D MI, n=3-6, p<0.05 ANOVA).

In summary, diabetes and experimental MI destabilize the atherosclerotic lesion, potentially explaining why patients with diabetes are at an increased risk of recurrent MI.


F. Kramer: None. A.M. Martinson: None. T. Papayannopoulou: None. C.E. Murry: Other Relationship; Self; Cytocardia. J.E. Kanter: None.


American Diabetes Association (1-16-IBS-153 to J.E.K.)

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