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Reversal of cyclosporine‐inhibited low‐density lipoprotein receptor activity in HepG2 cells by 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors
Author(s) -
Rayyes O A,
Wallmark A,
Florén C
Publication year - 1997
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510250433
Subject(s) - catabolism , hmg coa reductase , reductase , ldl receptor , hydroxymethylglutaryl coa reductase , coenzyme a , lipoprotein , receptor , enzyme , low density lipoprotein , chemistry , pharmacology , biochemistry , endocrinology , cholesterol , medicine , biology
Previously we have shown that cyclosporine inhibits low‐density lipoprotein (LDL) catabolism in HepG2 cells. This inhibition mainly occurs through reduced LDL‐receptor activity. 3‐Hydroxy‐3‐methylglutarylcoenzyme A (HMG‐CoA) reductase inhibitors up‐regulate LDL receptor activity with a subsequent increase in LDL uptake and degradation. In this study, in HepG2 cells, we investigated the effects of HMG‐CoA reductase inhibitors on cellular LDL catabolism in the presence of cyclosporine. Different concentrations of cyclosporine and HMG‐CoA reductase inhibitors, which were within the range of therapeutic concentrations used in humans, were added to the culture medium and the cellular LDL receptor activity was then measured. The results show that HMG‐CoA reductase inhibitors reverse the down‐regulatory effect of cyclosporine on LDL receptor activity, thus further supporting our previous findings and also providing a rationale for the already established treatment in cyclosporine‐induced hypercholesterolemia with HMG‐CoA reductase inhibitors.