Amiodarone-induced hypercholesterolemia is associated with a decrease in liver LDL receptor mRNA.
Amiodarone decreases plasma and tissue triiodothyronine (T3) and increases plasma cholesterol levels resembling changes seen during hypothyroidism. To elucidate the mechanism of amiodarone-induced hypercholesterolemia we investigated gene expression of three key proteins in cholesterol metabolism (cholesterol 7 alpha-hydroxylase, LDL receptor, HMG-CoA reductase) in livers of rats. Animals were treated with amiodarone or propylthiouracil (to induce mild hypothyroidism). The LDL receptor mRNA was downregulated (approximately 50%) in both amiodarone-treated and hypothyroid animals, while the other mRNA remained unchanged after 14-day treatment. The results suggest that amiodarone-induced hypercholesterolemia is associated with decreased LDL receptor mRNA levels.
Hudig
F
F
Department of Endocrinology, University of Amsterdam, The Netherlands.
Bakker
O
O
Wiersinga
W M
WM
D000638:Amiodarone / Q000633:toxicity*; D000818:Animals; D002790:Cholesterol 7-alpha-Hydroxylase / Q000096:biosynthesis / Q000378:metabolism; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics / Q000378:metabolism; D006937:Hypercholesterolemia / Q000139:chemically induced* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011441:Propylthiouracil / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
D012333:RNA, Messenger; D011973:Receptors, LDL; D011441:Propylthiouracil; D006903:Hydroxymethylglutaryl CoA Reductases; D002790:Cholesterol 7-alpha-Hydroxylase; D000638:Amiodarone