UP-REGULATION OF CHOLESTEROL-SYNTHESIS AFTER ACUTE REDUCTION OF LOW-DENSITY-LIPOPROTEIN BY APHERESIS IN NORMOCHOLESTEROLEMIC SUBJECTS - EVIDENCE FOR A THRESHOLD EFFECT

The influence of low density lipoproteins (LDL) in the plasma on the r egulation of cholesterol biosynthesis is not clear. We studied the cha nges in plasma mevalonic acid (MVA) concentration and the lathosterol/ cholesterol (L/C) ratio: which are well established indices of whole b ody cholesterol synthesis, in four normocholesterolaemic subjects afte r 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. A pheresis of 125% of the calculated plasma volume decreased plasma LDL- cholesterol by 69% to 0.9 +/- 0.2 mmol/l, with significant increases i n plasma MVA and L/C ratio on the day after the procedure. These resul ts imply that LDL-choresterol is an integral part of the sterol regula tory pool and suggest that plasma levels cannot be lowered below 1-1.4 mmol/l in normal subjects without upregulating cholesterol biosynthes is. (C) 1997 Elsevier Science Ireland Ltd.