C3H apoE(−/−) mice have less atherosclerosis than C57BL apoE(−/−) mice despite having a more atherogenic serum lipid profile

Wild-type C57BL mice are known to be susceptible to diet-induced atherosclerosis, whilst C3H mice are resistant. We investigated the effect of these background strains on the hyperlipidaemia and atherosclerosis that develops in mice deficient in apolipoprotein E (apoE(−/−)). Male and female apoE(−/−) mice on C3H/HeNHsd (C3H) and C57BL/6J (C57) backgrounds were fed atherogenic Western diet for 12 weeks. Serum cholesterol and triglyceride concentrations were measured and atherosclerosis quantified in the aortic sinus. C3H apoE(−/−) mice fed normal diet had 1.5–2 fold higher serum cholesterol levels than C57 apoE(−/−) mice and 4–5 fold higher serum triglyceride concentrations. Feeding Western diet caused a 4–5 fold increase in serum cholesterol in all mice, but levels of triglyceride were either attenuated or were unaffected in C3H apoE(−/−) and C57 apoE(−/−) mice, respectively. C3H apoE(−/−) mice had approximately 2 fold higher serum cholesterol and 4 fold higher triglyceride concentrations than the C57 apoE(−/−) mice throughout the study. Serum triglyceride concentrations were 35–108% higher in male C3H apoE(−/−) than female C3H apoE(−/−) mice. Most of the lipids were present in the very low density lipoprotein (VLDL)/chylomicron fraction in both strains of mice whether they were fed normal or Western diet. Notwithstanding the lower plasma lipid concentrations, atherosclerotic lesion areas were more than 2-fold larger in C57 apoE(−/−) than in C3H apoE(−/−) mice (males 68±11×103 vs 30±6×103, females 102±12×103 vs 41±8×103 μm2, mean±SEM).