Inhibition of cholesterol synthesis reduces low-density-lipoprotein apoprotein B production without decreasing very-low-density-lipoprotein apoprotein B synthesis in rabbits.
The kinetics of the apoprotein B (apo B) of very-low-density (VLDL; d less than 1.006) and low-density (LDL; d 1.019-1.063) lipoproteins were studied in six rabbits by using radioiodinated homologous lipoproteins, before and during oral administration of mevinolin (5 mg/kg per day), a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (EC 1.1.1.34), to explore the mechanism by which the drug reduces LDL synthesis. Before treatment LDL-apo B production greatly exceeded VLDL-apo B production in all animals, indicating that a large proportion of plasma LDL was derived from a VLDL-independent pathway. Five animals responded to mevinolin with a fall in plasma cholesterol (mean change - 53%; P less than 0.01). This was associated with a 66% decrease in LDL-apo B synthesis (P less than 0.05). In contrast, VLDL-apo B synthesis was unaffected by mevinolin. Furthermore, in all but one animal the decrement in LDL-apo B synthesis was greater than the rate of VLDL-apo B synthesis before treatment, demonstrating that mevinolin had reduced the VLDL-independent production of LDL.
D000818:Animals; D001053:Apolipoproteins / Q000096:biosynthesis* / Q000097:blood; D001055:Apolipoproteins B; D002784:Cholesterol / Q000096:biosynthesis* / Q000097:blood; D007700:Kinetics; D008079:Lipoproteins, VLDL / Q000096:biosynthesis* / Q000097:blood; D008148:Lovastatin; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology; D011817:Rabbits
D001053:Apolipoproteins; D001055:Apolipoproteins B; D008079:Lipoproteins, VLDL; D009281:Naphthalenes; C488866:apoLDL protein, Oryctolagus cuniculus; D002784:Cholesterol; D008148:Lovastatin