Cholestyramine treatment in early life of low-density lipoprotein receptor deficient Watanabe rabbits: decreased aortic cholesteryl ester accumulation and atherosclerosis in adult life.
Effect of cholestyramine treatment in early life of Watanabe heritable hyperlipidemic rabbits (an animal model lacking low-density lipoprotein receptor activity) on subsequent (6 months recovery) occurrence of natural atherosclerotic lesion and arterial cholesterol metabolism was investigated. Initial cholestyramine treatment decreased both plasma total cholesterol and HDL-cholesterol levels which normalized within 4 weeks after treatment was discontinued. At 9 months of age (age of occurrence of spontaneous atherosclerotic lesions), the extent of aortic atherosclerosis in cholestyramine pre-treated animals was modestly lower (P less than 0.05), as compared to controls, with a significant (P less than 0.05) decrease in aortic cholesteryl ester content. Furthermore, at the end of the recovery period aortic activity of acyl-CoA: cholesterol acyltransferase and neutral cholesterol esterase activity was significantly (P less than 0.05) lower in cholestyramine-pretreated animals. These studies show that early cholestyramine pre-treatment in a low-density lipoprotein receptor-deficient animal model causes persistent changes which might influence cholesteryl ester accumulation and atherogenesis in adult life, even after cholestyramine treatment is discontinued.
D000367:Age Factors; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001161:Arteriosclerosis / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism*; D002792:Cholestyramine Resin / Q000494:pharmacology*; D005260:Female; D008297:Male; D011817:Rabbits; D011973:Receptors, LDL / Q000172:deficiency*; D002787:Sterol Esterase / Q000378:metabolism; D002785:Sterol O-Acyltransferase / Q000378:metabolism
D002788:Cholesterol Esters; D011973:Receptors, LDL; D002792:Cholestyramine Resin; D002785:Sterol O-Acyltransferase; D002787:Sterol Esterase