Cyclosporine, low-density lipoprotein, and cholesterol

P. C. De Groen

Research output: Contribution to journalArticle

144 Citations (Scopus)

Abstract

Lipoproteins are known to be able to transport a variety of drugs. This report suggests that low-density lipoprotein not only functions as an important carrier of cyclosporine in plasma but also facilitates transport of cyclosporine across the cell membrane by means of the low-density lipoprotein receptor. Such a mechanism would explain (1) the similar tissue distribution of cyclosporine and the low-density lipoprotein receptor, (2) the increase in immunosuppression and toxicity with low total serum cholesterol levels, and (3) the relative absence of immunosuppression and toxicity with high levels of cyclosporine in the blood in patients with hypertriglyceridemia. In addition to receptor-mediated uptake, a disturbance of the blood-brain barrier is suggested as an explanation of the high frequency of cyclosporine-induced central nervous system toxicity after liver transplantation. Cyclosporine-induced inhibition of the mitochondrial steroid 26-hydroxylase, an enzyme involved in the formation of bile acids from cholesterol and deficient in patients with cerebrotendinous xanthomatosis, may cause or contribute to the observed central nervous system toxicity. It also may explain the similar clinical features of cyclosporine-induced central nervous system toxicity and cerebrotendinous xanthomatosis.

Original languageEnglish (US)
Pages (from-to)1012-1021
Number of pages10
JournalMayo Clinic Proceedings
Volume63
Issue number10
StatePublished - 1988

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LDL Cholesterol
Cyclosporine
Cerebrotendinous Xanthomatosis
Central Nervous System
LDL Receptors
LDL Lipoproteins
Immunosuppression
Steroid Hydroxylases
Cholesterol
Hypertriglyceridemia
Tissue Distribution
Blood-Brain Barrier
Bile Acids and Salts
Liver Transplantation
Lipoproteins
Cell Membrane
Enzymes
Serum
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Cyclosporine, low-density lipoprotein, and cholesterol. / De Groen, P. C.

In: Mayo Clinic Proceedings, Vol. 63, No. 10, 1988, p. 1012-1021.

Research output: Contribution to journalArticle

De Groen, PC 1988, 'Cyclosporine, low-density lipoprotein, and cholesterol', Mayo Clinic Proceedings, vol. 63, no. 10, pp. 1012-1021.
De Groen, P. C. / Cyclosporine, low-density lipoprotein, and cholesterol. In: Mayo Clinic Proceedings. 1988 ; Vol. 63, No. 10. pp. 1012-1021.
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