Effects of cholesterol loading on autoimmune MRL-lpr/lpr mice: susceptibility to hypercholesterolemia and aortic cholesterol deposition.

Autoimmune MRL-lpr/lpr (MRL/l) mice, with a systemic lupus erythematosus-like disease, were shown to spontaneously develop hyperlipidemia and yet be susceptible to diet-induced hypercholesterolemia and aortic cholesterol deposition. Control animals on a basal diet showed significant increases in the serum total cholesterol, phospholipids, triglycerides, high density lipoprotein (HDL)-cholesterol and lipid peroxide levels, but a significant decline in the serum lecithin: cholesterol acyltransferase (LCAT) activity compared to those of 5-week-old mice. Animals on the high-cholesterol diet showed a rapid rise in serum total cholesterol to a plateau level (800 mg/100 ml) that was approximately 2.5 times higher than that in the control animals on a basal diet. However, the levels of serum triglycerides, HDL-cholesterol and lipid peroxides significantly decreased (by 61%, 23% and 53%, respectively) compared to those of the control animals, whereas LCAT activity and phospholipid level were not affected. The aortic contents of total cholesterol, free cholesterol and cholesteryl ester were significantly higher (by 35%, 36% and 31%, respectively) in animals fed the high-cholesterol diet than the control animals. These findings suggest that MRL/l mice are susceptible to diet-induced hypercholesterolemia and aortic cholesterol deposition.