Lovastatin therapy in familial dysbetalipoproteinemia: effects on kinetics of apolipoprotein B.
Familial dysbetalipoproteinemia is characterized by hyperlipidemia, increases in beta-migrating, very low density lipoproteins (beta-VLDL), and homozygosity for apolipoprotein E2 (apo E2). In this study, 3 patients with familial dysbetalipoproteinemia were treated with lovastatin, and kinetics for apolipoprotein B (apo B) were determined in control and drug treatment periods. Multicompartmental analyses of apo B kinetics in VLDL and in low density lipoproteins (LDL) were carried out. Lovastatin therapy generally lowered plasma concentrations of apo B and cholesterol in VLDL and LDL. The reductions in concentrations were due mainly to a decrease in transport (production) rates for these fractions. Indeed, the fractional clearance rate (FCR) for LDL-apo B was reduced during lovastatin therapy. The decreased transport rate for VLDL-apo B and LDL-apo B could have been due to an inhibition of the synthesis of lipoproteins containing apo B. An alternate explanation is that lovastatin promoted direct removal of a rapidly-catabolized fraction of VLDL-apo B that is a precursor for longer-lived lipoproteins in the circulation; this mechanism could decrease input rates of identifiable lipoprotein species and retard their clearance because of "saturation" of LDL receptors by more rapidly removed lipoproteins. Finally, both mechanisms, i.e., decreased production and increased clearance of lipoproteins, may have contributed to the fall in VLDL-apo B and LDL-apo B concentrations during lovastatin therapy.
Vega
G L
GL
Center for Human Nutrition, University of Texas Health Science Center, Dallas 75235-9051.
East
C
C
Grundy
S M
SM
D000328:Adult; D001055:Apolipoproteins B / Q000097:blood*; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL; D005260:Female; D015248:Gemfibrozil; D006801:Humans; D006952:Hyperlipoproteinemia Type III / Q000097:blood* / Q000188:drug therapy; D007700:Kinetics; D008079:Lipoproteins, VLDL / Q000097:blood; D008148:Lovastatin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010421:Pentanoic Acids / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood
D001055:Apolipoproteins B; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D008079:Lipoproteins, VLDL; D010421:Pentanoic Acids; D014280:Triglycerides; D002784:Cholesterol; D008148:Lovastatin; D015248:Gemfibrozil