Persistent abnormalities in lipoprotein composition and cholesteryl ester transfer following lovastatin treatment

J. D. Bagdade*, J. T. Lane, N. Stone, M. C. Ritter, P. V. Subbaiah

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Optimally effective lipid-lowering agents should not only restore plasma lipids to normal levels but also correct potentially atherogenic alterations in lipoprotein composition and function often present in hyperlipidemic patients. Lovastatin, a competitive inhibitor of cholesterol biosynthesis, clearly lowers plasma cholesterol levels. Its effects on lipoprotein composition and cholesteryl ester transfer (CET), a key step in reverse cholesterol transport, however, are not known. Since abnormalities in CET and lipoprotein composition are present in patients with hypercholesterolemia, we studied these parameters of plasma lipoprotein transport in twelve hypercholesterolemic (HC; Type IIa) subjects (six male, six female) before and 2 months after lovastatin treatment (20 mg qd). Before lovastatin, the free cholesterol (FC)/lecithin (L) ratio in plasma, a new index of cardiovascular risk that reflects lipoprotein surface composition, was abnormally increased (1.18 ± 0.26 vs controls 0.83 ± 0.14; P < 0.001) in very low density lipoproteins (VLDL) and high density lipoprotein-3 (HDL3), and remained so after treatment despite significant declines in whole plasma cholesterol (311.7 ± 68.2 vs 215.6 ± 27.2 mg/dl; P < 0.001), low density lipoprotein (LDL)-cholesterol (206.3 ± 47.9 vs 146.8 ± 29.4; P < 0.001), and apolipoprotein B (149 ± 30 vs 110 ± 17; P < 0.005). The percentage of cholesteryl ester in plasma that was esterified in these patients was slightly higher than that of the reference group before lovastatin, and fell significantly (P < 0.025) after treatment to levels that reflected a relative increase of almost 20% in lipoprotein FC. In contrast to the minimal amount of cholesteryl ester that was transferred initially from HDL to VLDL + LDL in normolipidemic control subjects, CET in all HC patients before lovastatin was significantly accelerated at 1, 2, and 4 h (P < 0.001). Two months treatment with lovastatin had no discernible effect on CET which remained abnormally increased. These findings indicate that potentially atherogenic abnormalities in lipoprotein composition and function present in patients with hypercholesterolemia persist despite near normalization of plasma lipids after treatment with lovastatin.

Original languageEnglish (US)
Pages (from-to)1263-1269
Number of pages7
JournalJournal of lipid research
Volume31
Issue number7
StatePublished - 1990

Keywords

  • Free cholesterol/lecithin ratio
  • HDL
  • LDL
  • VLDL
  • hypercholesterolemia

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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