title: Hypercholesterolaemia: simvastatin and pravastatin alter cholesterol metabolism by different mechanisms.
abstract: The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor simvastatin, reduced low-density-lipoprotein (LDL) cholesterol in hypercholesterolaemic patients by 40% (P less than 0.001). The reduction in LDL cholesterol was accompanied by a significant decrease in the esterified/free cholesterol ratio of the patients' LDL from 2.51 +/- 0.13 to 2.06 +/- 0.14 (P less than 0.01). This change led to a significant increase (P less than 0.05) in the capacity of the LDL to suppress [14C]acetate incorporation into cholesterol in mononuclear leucocytes. Furthermore, [14C]acetate incorporation into the patients mononuclear leucocytes was significantly lower (P less than 0.02) following drug treatment (117 +/- 22 vs. 162 +/- 29 nmol/mg cell protein). Comparison of simvastatin with another HMG-CoA reductase inhibitor pravastatin, showed similar reduction in LDL cholesterol. Pravastatin treatment however, did not result in a reduction in the LDL esterified/free cholesterol ratio or in the changes in cellular cholesterol synthesis and its regulation by LDL which accompanied simvastatin treatment. The activity of the enzyme acyl-coenzyme A: cholesterol acyltransferase (ACAT) in patients' mononuclear cells remained unchanged after treatment with either drug. Results of the study show that while the drugs are equally effective in lowering LDL cholesterol, simvastatin has additional compositional effects on LDL which increase its capacity to regulate mononuclear leucocyte cholesterologenesis.
authors.affiliation: Royal College of Surgeons, Dublin, Ireland.
authors.forename: D
authors.initials: D
authors.lastname: Owens
authors.forename: P
authors.initials: P
authors.lastname: Collins
authors.forename: A
authors.initials: A
authors.lastname: Johnson
authors.forename: O
authors.initials: O
authors.lastname: Tighe
authors.forename: K
authors.initials: K
authors.lastname: Robinson
authors.forename: G H
authors.initials: GH
authors.lastname: Tomkin
mesh_terms: D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents; D002784:Cholesterol / Q000096:biosynthesis / Q000378:metabolism*; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D025782:Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent; D006937:Hypercholesterolemia / Q000188:drug therapy*; D007962:Leukocytes / Q000378:metabolism; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008875:Middle Aged; D009281:Naphthalenes / Q000494:pharmacology* / Q000627:therapeutic use; D017035:Pravastatin; D019821:Simvastatin
chemical_list: D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009281:Naphthalenes; D002784:Cholesterol; D008148:Lovastatin; D019821:Simvastatin; D025782:Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent; D017035:Pravastatin