Evidence of extensive atherosclerosis, coronary artery disease and myocardial infarction in the ApoE:Ins2 mouse fed a western diet.

BACKGROUND AND AIMS

Diabetic patients with no history of cardiac infarction have a prevalence of coronary atherosclerosis and a risk of heart attack equivalent to euglycemic patients who have coronary atherosclerosis and have suffered a prior myocardial infarction. Although several murine models of diabetes have been established, none of these show indications of cardiac events. In an attempt to establish a diabetic mouse model with coronary atherosclerosis and myocardial injury, we have fed hyperglycemic ApoE:Ins2 mice a western diet to enhance the dyslipidemic phenotype.

METHODS

Five-week-old ApoE:Ins2 mice and ApoE controls were fed a diet, 0.15% cholesterol and 21% anhydrous milk lipids, until 25 weeks of age. Changes in lifespan, clinical and metabolic parameters were evaluated as well as atherosclerosis and heart injury.

RESULTS

In comparison to male ApoE, male ApoE:Ins2 mice presented with chronic hyperglycemia (30.8 ± 1.2 mM vs. 9.3 ± 0.5 mM) accompanied by extremely high levels of total plasma cholesterol (49.3 ± 6.3 mM vs. 30.1 ± 1.5 mM) and triglycerides (11.6 ± 1.7 mM vs. 2.36 ± 0.18 mM). These mice have atherosclerosis at multiple vascular sites, including aortic sinus, ascending and descending aorta, brachiocephalic artery and coronary arteries. In addition, myocardial infarcts and a significant reduction of the lifespan (close to 20% of survival vs. other groups) were observed. Distinctively, both strains of female mice presented a parallel increase in plasma lipids, atherosclerosis, and no effects on mortality.

CONCLUSIONS

We have established a diabetic mouse model, the western-diet-fed male ApoE:Ins2 mouse, with profound cardiovascular disease involving extensive atherosclerosis, coronary artery disease and myocardial infarct resulting in shortened lifespan.