AMIODARONE-INDUCED HYPERCHOLESTEROLEMIA IS ASSOCIATED WITH A DECREASEIN LIVER LDL RECEPTOR MESSENGER-RNA

Amiodarone decreases plasma and tissue triiodothyronine (T-3) and incr eases plasma cholesterol levels resembling changes seen during hypothy roidism. To elucidate the mechanism of amiodarone-induced hypercholest erolemia we investigated gene expression of three key proteins in chol esterol metabolism (cholesterol 7 alpha-hydroxylase, LDL receptor, HMG -CoA reductase) in livers of rats. Animals were treated with amiodaron e or propylthiouracil (to induce mild hypothyroidism). The LDL recepto r mRNA was downregulated (approximate to 50%) in both amiodarone-treat ed and hypothyroid animals, while the other mRNA remained unchanged af ter 14-day treatment. The results suggest that amiodarone-induced hype rcholesterolemia is associated with decreased LDL receptor mRNA levels .