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.