The results in rodent models of atherosclerosis are not interchangeable: The influence of diet and strain

The determinant factors for the development of atherosclerosis in response to dietary cholesterol were examined in two animal models to assess the comparability of results. We studied 128 male Apo E−/− and 128 LDLr−/− mice randomly assigned to baseline (n = 8) and 5 groups (n = 24 each) that differed only in their dietary fat and cholesterol supplements. At 10, 16, 24 and 32 weeks of age, 8 animals from each group were sequentially sacrificed and the variables analyzed. The lesion sizes changed at different rates but they were predictable and did not differ in complexity. We observed, however, significant differences between strains, particularly in the constitutive expression of liver genes, their metabolic response to dietary cholesterol, their feeding behaviour, their glucose tolerance and the gain in body weight. Both strains presented characteristics that resemble steatohepatitis but manifestations were more severe in LDLr−/− mice. The divergent responses indicate that the choice of the diet and the model should be carefully considered in atherosclerosis studies and extrapolations interpreted with caution.