The rebound of lipoproteins after LDL-apheresis. Effects on chemical composition and LDL-oxidizability.
The changes in low density lipoprotein (LDL) composition and oxidizability after LDL-apheresis (LA) using dextran sulfate cellulose columns were evaluated in 12 hypercholesterolemic men (mean+/-S.D. total cholesterol (TC) 9.7+/-1.8 mmol/l). After 10-20 months on biweekly LA combined with simvastatin 40 mg per day immediate pre-apheresis levels of TC, LDL-cholesterol, and apolipoprotein B were decreased to 5.3+/-1.3 mmol/l, 3.3+/-1.2 mmol/l, and 1.6+/-0.4 g/l, respectively, whereas apheresis induced mean acute reductions of 61, 78, and 76%, respectively. Measurements of copper-induced LDL-oxidizability in vitro showed an increased resistance against oxidation after LA until day 3 post-treatment: lag time (min) (day 0 (before LA) versus day 1 (post-LA)) 112+/-27 versus 130+/-26 (P=0.001), maximal rate of diene production (nmol/min per mg LDL) 11.1+/-2.7 versus 9.1+/-2.1 (P=0.001), and time to maximal diene production (min) 186+/-39 versus 209+/-35 (P=0. 001). Analysis of the chemical composition of LDL revealed a 25% (P<0.001) reduced content of cholesteryl esters and a decrease of the cholesterol to protein ratio of 1.20+/-0.25 to 0.70+/-0.22 (P<0. 001) through the 3rd day post-LA. Linoleic acid and arachidonic acid content of LDL decreased 11 and 18%, respectively, at the expense of palmitic acid. Vitamin E levels (mg/l) were significantly lowered due to reduction of the lipoprotein pool by apheresis; however, vitamin E content of LDL did not change in the days after apheresis when expressed per g protein or per micromol linoleic acid. The changes in fatty acid pattern were strongly associated with changes in LDL-oxidizability indices (P</=0.01). Thus, LA effectively decreased LDL pool size, inducing the presence of less buoyant lipoproteins, which were less susceptible to in vitro oxidation. This was not explained by changes in vitamin E levels, but by short-term changes in the fatty acids composition.
Kroon
A A
AA
Department of Medicine, Division of General Internal Medicine, 541 AIG, University Hospital Nijmegen, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
Demacker
P N
PN
Kleinveld
H A
HA
Stalenhoef
A F
AF
D001055:Apolipoproteins B / Q000097:blood; D001781:Blood Component Removal; D002784:Cholesterol / Q000097:blood; D002788:Cholesterol Esters / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003131:Combined Modality Therapy; D005227:Fatty Acids / Q000032:analysis; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood* / Q000188:drug therapy / Q000628:therapy; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D019821:Simvastatin / Q000627:therapeutic use; D014810:Vitamin E / Q000032:analysis
D001055:Apolipoproteins B; D002788:Cholesterol Esters; D008078:Cholesterol, LDL; D005227:Fatty Acids; D000960:Hypolipidemic Agents; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D014810:Vitamin E; D002784:Cholesterol; D019821:Simvastatin