title: [Effect of pravastatin on hepatic cholesterol metabolism].
abstract: BACKGROUND
  Inhibitors of the rate-limiting enzyme of cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are now used frequently to treat hypercholesterolemia. We studied the effects of specific inhibition of cholesterol synthesis by one of these agents (pravastatin) on the hepatic metabolism of cholesterol in patients with gallstone disease who were scheduled to undergo cholecystectomy.
  
  
  METHODS
  Ten patients were treated with pravastatin (20 mg twice a day) for three weeks before cholecystectomy; 20 patients not treated served as controls. A liver specimen was obtained from each patient at operation, and the activities of rate-determining enzymes in cholesterol metabolism as well as low-density-lipoprotein (LDL)-receptor binding activity were determined.
  
  
  RESULTS
  Pravastatin therapy reduced plasma total cholesterol by 26 percent and LDL cholesterol by 39 percent (p less than 0.005). Serum levels of free lathosterol, a precursor of cholesterol whose concentration reflects the rate of cholesterol synthesis in vivo, decreased by 63 percent (p less than 0.005), indicating reduced de novo biosynthesis of cholesterol. Microsomal HMG-CoA reductase activity, when analyzed in vitro in the absence of the inhibitor, was increased 11.8-fold (1344 +/- 311 vs. 105 +/- 14 pmol per minute per milligram of protein in the controls; p less than 0.001). The expression of LDL receptors was increased by 180 percent (p less than 0.005), whereas the activities of cholesterol 7 alpha-hydroxylase (which governs bile acid synthesis) and of acyl-coenzyme A: cholesterol O-acyltransferase (which regulates cholesterol esterification) were unaffected by treatment.
  
  
  CONCLUSIONS
  Inhibition of hepatic HMG-CoA reductase by pravastatin results in an increased expression of hepatic LDL receptors, which explains the lowered plasma levels of LDL cholesterol.
authors.affiliation: Abteilung für Innere Medizin, Universitätsklinik Huddinge/Schweden.
authors.forename: E
authors.initials: E
authors.lastname: Reihnér
authors.forename: M
authors.initials: M
authors.lastname: Rudling
authors.forename: D
authors.initials: D
authors.lastname: Ståhlberg
authors.forename: L
authors.initials: L
authors.lastname: Berglund
authors.forename: S
authors.initials: S
authors.lastname: Ewerth
authors.forename: I
authors.initials: I
authors.lastname: Björkhem
authors.forename: K
authors.initials: K
authors.lastname: Einarsson
authors.forename: B
authors.initials: B
authors.lastname: Angelin
mesh_terms: D000328:Adult; D000368:Aged; D002769:Cholelithiasis / Q000201:enzymology*; D002784:Cholesterol / Q000097:blood*; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000627:therapeutic use*; D017035:Pravastatin; D011973:Receptors, LDL / Q000187:drug effects
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009281:Naphthalenes; D011973:Receptors, LDL; D002784:Cholesterol; D017035:Pravastatin
vernacular_title: Einfluss von Pravastatin auf den hepatischen Cholesterinmetabolismus.