Lowering Plasma Cholesterol by Raising LDL Receptors — Revisited

Thirty-one years ago, Mabuchi and colleagues1 reported in the Journal that a statin called compactin reduced plasma low-density lipoprotein (LDL) cholesterol levels by 29% in patients with heterozygous familial hypercholesterolemia. This drug inhibits an early step in cholesterol synthesis catalyzed by the enzyme 3-hydroxy-3-methylglutaryl–coenzyme A (HMG-CoA) reductase. In an accompanying editorial entitled “Lowering Cholesterol by Raising LDL Receptors,” Brown and Goldstein2 noted that heterozygotes for familial hypercholesterolemia have a deficiency of LDL receptors on cells, resulting in reduced cholesterol uptake by cells and high levels of cholesterol in the plasma. They explained that cholesterol levels within cells are tightly controlled, . . .