Effects of lovastatin therapy on guinea pig low density lipoprotein composition and metabolism

Lars Berglund, M. F. Sharkey, R. L. Elam, J. L. Witztum

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Lovastatin therapy is known to induce hepatic low density lipoprotein (LDL) receptor mRNA and LDL receptor activity. Yet, in studies in humans and animals it has been difficult to demonstrate an enhancement of the plasma fractional catabolic rate (FCR) of an injected LDL tracer during lovastatin therapy. One explanation may be that the composition of the LDL tracer may also change during therapy, independently affecting LDL clearance. To test this possibility we fed guinea pigs lovastatin, which led to a decrease in their plasma LDL cholesterol levels. Composition studies showed that LDL isolated from lovastatin-treated guinea pigs was slightly cholesterol-depleted and triglyceride-enriched when compared to LDL isolated from control animals. Several independent lines of investigation documented that a substantial increase in hepatic LDL receptor activity occurred in response to the lovastatin treatment. Consistent with this, when a single LDL tracer was injected into control and lovastatin-treated guinea pigs, the FCR was always more rapid in the lovastatin-treated animals. However, when LDL isolated from lovastatin-treated animals (L-LDL) was simultaneously injected intravenously with LDL isolated from control animals (C-LDL) the FCR of the C-LDL was always more rapid than that of the L-LDL. When one compared the FCR of C-LDL determined in control animals with the FCR of L-LDL determined in lovastatin animals there was no difference. Possible explanations for these paradoxical findings are discussed. These data demonstrate that lovastatin therapy affects both hepatic LDL receptor activity as well as the intrinsic metabolic properties of plasma LDL.

Original languageEnglish (US)
Pages (from-to)1591-1600
Number of pages10
JournalJournal of Lipid Research
Volume30
Issue number10
StatePublished - 1989

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Lovastatin
LDL Lipoproteins
Metabolism
Guinea Pigs
Chemical analysis
Animals
LDL Receptors
Therapeutics
Plasmas
Liver

ASJC Scopus subject areas

  • Endocrinology

Cite this

Effects of lovastatin therapy on guinea pig low density lipoprotein composition and metabolism. / Berglund, Lars; Sharkey, M. F.; Elam, R. L.; Witztum, J. L.

In: Journal of Lipid Research, Vol. 30, No. 10, 1989, p. 1591-1600.

Research output: Contribution to journalArticle

Berglund, Lars ; Sharkey, M. F. ; Elam, R. L. ; Witztum, J. L. / Effects of lovastatin therapy on guinea pig low density lipoprotein composition and metabolism. In: Journal of Lipid Research. 1989 ; Vol. 30, No. 10. pp. 1591-1600.
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