Oxidized cholesterol in the diet is a source of oxidized lipoproteins in human serum.
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.
Staprans
Ilona
I
Department of Veterans Affairs Medical Center, University of California, San Francisco 94143, USA. stapan@itsa.ucsf.edu
Pan
Xian-Mang
XM
Rapp
Joseph H
JH
Feingold
Kenneth R
KR
D002352:Carrier Proteins; D016022:Case-Control Studies; D002784:Cholesterol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism*; D053480:Cholesterol Ester Transfer Proteins; D053298:Chylomicron Remnants; D002914:Chylomicrons / Q000378:metabolism; D004032:Diet; D006023:Glycoproteins; D006801:Humans; D006952:Hyperlipoproteinemia Type III / Q000097:blood / Q000378:metabolism; D008074:Lipoproteins / Q000097:blood* / Q000378:metabolism; D010084:Oxidation-Reduction; D013997:Time Factors
C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D053298:Chylomicron Remnants; D002914:Chylomicrons; D006023:Glycoproteins; D008074:Lipoproteins; C002415:cholesterol alpha-oxide; D002784:Cholesterol