The aim of this study was to determine in humans whether oxidized
cholesterol in the diet is absorbed and contributes to the pool of oxidized
lipids in
circulating lipoproteins. When a meal containing 400 mg cholestan-5alpha,6alpha-epoxy-3beta-ol (alpha-epoxy
cholesterol) was fed to six controls and three subjects with
Type III hyperlipoproteinemia, alpha-epoxy
cholesterol in serum was found in
chylomicron/
chylomicron remnants (CM/RM) and endogenous (VLDL,
LDL, and
HDL) lipoproteins. In controls, alpha-epoxy
cholesterol in CM/RM was decreased by 10 h, whereas in endogenous
lipoproteins it remained in the circulation for 72 h. In subjects with
Type III hyperlipoproteinemia, alpha-epoxy
cholesterol was mainly in CM/RM. In vitro incubation of the CM/RM fraction containing alpha-epoxy
cholesterol with human
LDL and HDL that did not contain alpha-epoxy
cholesterol resulted in a rapid transfer of oxidized
cholesterol from CM/RM to both
LDL and HDL. In contrast, no transfer was observed when human serum was substituted with rat serum, suggesting that
cholesteryl ester transfer protein is mediating the transfer. Thus, alpha-epoxy
cholesterol in the diet is incorporated into the CM/RM fraction and then transferred to
LDL and HDL, contributing to
lipoprotein oxidation. Moreover,
LDL containing alpha-epoxy
cholesterol displayed increased susceptibility to further
copper oxidation in vitro. It is possible that oxidized
cholesterol in the diet accelerates
atherosclerosis by increasing oxidized
cholesterol levels in circulating
LDL and
chylomicron remnants.