Regulation of low density lipoprotein apoprotein B metabolism by lovastatin and cholestyramine in miniature pigs: effects on LDL composition and synthesis of LDL subfractions.
A major factor in the regulation of low density lipoprotein (LDL) apoprotein B (apo B) concentrations in miniature pigs is the direct synthesis of LDL apo B. LDL apo B derived from plasma very low density lipoproteins (VLDL) accounts for only 20% to 30% of total LDL synthesis. Treatment with lovastatin and cholestyramine can inhibit the direct synthesis pathway in this species, thereby lowering LDL apo B concentrations. The present study was carried out to determine if lovastatin alone was as effective as in combination with cholestyramine. The possibility that the direct synthesis pathway was confined to a specific subclass of LDL and the effect of lovastatin and cholestyramine on the metabolism of LDL subfractions were also investigated. Homologous 125I-VLDL and 131I-LDL were injected into miniature pigs during a control period and again following 18 days of treatment with lovastatin (1.2 mg/kg/d, n = 4) or in combination with cholestyramine (1.0 g/kg/d, n = 4). Kinetic analysis of apo B specific activity curves following lovastatin treatment indicated that LDL apo B pool size was decreased by 25% (P less than .025), which was due entirely to a 70% (P less than .025) decrease in the direct synthesis of LDL apo B, since VLDL-derived apo B, and LDL fractional catabolic rate (FCR) were not affected. Parameters of VLDL apo B metabolism were not affected. Lovastatin in combination with cholestyramine was more effective than lovastatin alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Huff
M W
MW
Department of Medicine, Robarts Research Institute, University of Western Ontario, London, Canada.
Telford
D E
DE
D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D002792:Cholestyramine Resin / Q000008:administration & dosage / Q000494:pharmacology*; D004032:Diet; D004338:Drug Combinations; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000097:blood / Q000378:metabolism; D008148:Lovastatin / Q000008:administration & dosage / Q000494:pharmacology*; D013552:Swine; D013556:Swine, Miniature; D014280:Triglycerides / Q000097:blood
D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004338:Drug Combinations; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride; D002792:Cholestyramine Resin; D008148:Lovastatin