DIAZEPAM INHIBITS CHOLESTEROL ESTERIFICATION BY ARTERIAL ACAT AND PLASMA LCAT, INVITRO

Benzodiazepine drugs have been reported to have antiatherosclerotic effects in rabbits and roosters and to alter the pattern of circulating lipoproteins in man. The mechanism(s) of these effects has not been elucidated. Diazepam, the most widely used benzodiazepine, apparently is an inhibitor of cholesterol esterification by ACAT [acylcoenzyme A: cholesterol acyltransferase] in vitro in atheromatous rabbit aortas, in microsomes isolated from atheromatous rabbit aortas, and in normal rat aortas. Diazepam also inhibited LCAT [lecithinicholesterol acyltransferase] in plasma from man, monkey, rabbit and rat, in vitro. The ability of diazepam to inhibit these enzyme systems may offer insight into possible in vivo mechanisms of action against atherosclerosis and of lipoprotein modification.