Lipoprotein levels in genetically selected mice with increased susceptibility to atherosclerosis.

Abstract

Male mice of two inbred strains, C57BR/cdJ and CBA/J, were maintained either on an atherogenic diet rich in cholesterol (5%) and saturated fat (30%) or on a control Purina Laboratory Chow diet. After 3 weeks on a 90% atherogenic/10% chow diet, the C57BR/cdJ mice showed a fivefold increase in plasma total cholesterol levels, while the CBA/J strain indicated only a twofold increase. On the atherogenic diet, both groups of animals showed marked increases in a lipoprotein of a broad density spectrum (1.006 greater than d less than 1.063) with prebeta and beta mobility on agarose gel electrophoresis, but the C57BR/cdJ strain showed a greater increase than the CBA/J strain. The very low density lipoprotein (VLDL) contained predominantly lipoprotein of prebeta mobility, while intermediate density lipoprotein (IDL) and low density lipoprotein (LDL) contained lipoprotein of beta-mobility. In both strains, the major lipid component in this lipoprotein was cholesteryl ester and both strains showed large amounts of an apoprotein (apo) with E mobility as defined for known apoproteins by sodium dodecyl sulfate polyacrylamide gel electrophoresis or by isoelectric focusing on polyacrylamide-urea disc gels. The phosphatidylcholine/free cholesterol ratio of the VLDL, IDL, and LDL fractions isolated from the C57BR/cdJ mice on the atherogenic diet (0.76 to 0.95) was noticeably lower than that (1.10 to 1.19) from the CBA/J mice maintained on the same diet. There was a marked decrease in the high density lipoprotein (HDL) fraction in both strains of mice on the atherogenic diet, but a greater reduction in the HDL level of the C57BR/cdJ strain with a 50% decrease in the phosphatidylcholine/free cholesterol ratio.(ABSTRACT TRUNCATED AT 250 WORDS)