Upregulation of cholesterol synthesis after acute reduction of low density lipoprotein by apheresis in normocholesterolaemic subjects: evidence for a threshold effect

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 synt...

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Bibliographic Details
Published in:Atherosclerosis 1997-12, Vol.135 (2), p.257-262
Main Authors: Pfohl, Martin, Naoumova, Rossitza P, Neuwirth, Clare, Sussekov, Andrey, Smykowski, J, Rendell, Nigel B, Taylor, Graham W, Seif, F.J, Thompson, Gilbert R
Format: Article
Language:English
Subjects:
Adult
Biological and medical sciences
Blood Component Removal
Cholesterol - biosynthesis
Cholesterol - blood
Cholesterol, LDL - blood
Cholesterol, LDL - physiology
Fundamental and applied biological sciences. Psychology
HMG-CoA reductase inhibitor
Humans
Hydroxymethylglutaryl CoA Reductases - blood
Lathosterol
Lipids. Glycolipids
Lipoproteins, LDL - blood
Male
Metabolisms and neurohumoral controls
Mevalonic acid
Mevalonic Acid - blood
Simvastatin
Up-Regulation
Vertebrates: anatomy and physiology, studies on body, several organs or systems
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Summary: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.
ISSN:0021-9150
1879-1484
DOI:10.1016/S0021-9150(97)00173-1