title: Upregulation of cholesterol synthesis after acute reduction of low density lipoprotein by apheresis in normocholesterolaemic subjects: evidence for a threshold effect.
abstract: The influence of low density lipoproteins (LDL) in the plasma on the regulation of cholesterol biosynthesis is not clear. We studied the changes in plasma mevalonic acid (MVA) concentration and the lathosterol/cholesterol (L/C) ratio, which are well established indices of whole body cholesterol synthesis, in four normocholesterolaemic subjects after each had undergone LDL apheresis on two occasions. LDL apheresis of 75% of the calculated plasma volume reduced LDL-cholesterol by 44% to 1.5 +/- 0.2 mmol/l without changing plasma MVA levels or L/C ratios. Apheresis of 125% of the calculated plasma volume decreased plasma LDL-cholesterol by 69% to 0.9 +/- 0.2 mmol/l, with significant increases in plasma MVA and L/C ratio on the day after the procedure. These results imply that LDL-cholesterol is an integral part of the sterol regulatory pool and suggest that plasma levels cannot be lowered below 1-1.4 mmol/l in normal subjects without upregulating cholesterol biosynthesis.
authors.affiliation: Eberhard-Karls-Universität Tübingen, Medizinische Klinik und Poliklinik, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Pfohl
authors.forename: R P
authors.initials: RP
authors.lastname: Naoumova
authors.forename: C
authors.initials: C
authors.lastname: Neuwirth
authors.forename: A
authors.initials: A
authors.lastname: Sussekov
authors.forename: J
authors.initials: J
authors.lastname: Smykowski
authors.forename: N B
authors.initials: NB
authors.lastname: Rendell
authors.forename: G W
authors.initials: GW
authors.lastname: Taylor
authors.forename: F J
authors.initials: FJ
authors.lastname: Seif
authors.forename: G R
authors.initials: GR
authors.lastname: Thompson
mesh_terms: D000328:Adult; D001781:Blood Component Removal; D002784:Cholesterol / Q000096:biosynthesis* / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood / Q000502:physiology; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008798:Mevalonic Acid / Q000097:blood; D015854:Up-Regulation
chemical_list: D008078:Cholesterol, LDL; D008077:Lipoproteins, LDL; C001521:lathosterol; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D008798:Mevalonic Acid