Metabolism of apolipoprotein B in primary moderate hypercholesterolaemia: effects of acipimox and cholestyramine therapy.
The effects of combined therapy with acipimox (1250 mg/day) and cholestyramine (20 g/day) were examined in a group of 7 subjects with primary moderate hypercholesterolaemia (total cholesterol >=7 mmol/L). Radiolabeled VLDL subfraction turnovers were performed at baseline, during acipimox therapy and during combined therapy. Acipimox and combined therapies lowered plasma low density lipoprotein (LDL)-cholesterol by 20% (P<0.001) and 27% (P<0.001) respectively. The marked fall in LDL-cholesterol associated with acipimox therapy, was due to a reduced production rate of LDL (apolipoprotein) apoB. This is shown to be a result of reduced direct LDL apoB production, reduced IDL to LDL transfer consistent with inhibition of hepatic triglyceride lipase, and with a reduction in the overall throughput of VLDL1 apoB. With combined therapy both reduced production and increased catabolism of apoB containing LDL precursors and of LDL itself have to be invoked to explain the fall in plasma LDL-cholesterol.
Gaw
A
A
Royal Infirmary University/NHS Trust, Dept of Pathological Biochemistry, 4th Floor Queen Elizabeth Building, Glasgow, G31 2ER, UK.
Packard
C J
CJ
Lindsay
G M
GM
Collins
S M
SM
Lorimer
A R
AR
Shepherd
J
J
D000328:Adult; D001055:Apolipoproteins B / Q000097:blood*; D002792:Cholestyramine Resin / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000008:administration & dosage*; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000008:administration & dosage*
D001055:Apolipoproteins B; D000960:Hypolipidemic Agents; D008079:Lipoproteins, VLDL; D011719:Pyrazines; D002792:Cholestyramine Resin; C027696:acipimox