Oxidized cholesterol in the diet is a source of oxidized lipoproteins in human serum

Ilona Staprans, Xianmang Pan, Joseph H. Rapp, and Kenneth R. Feingold

Surgery, VA Medical Center, san francisco, Ca 94121

Corresponding Author: stapan{at}itsa.ucsf.edu

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 alpha-epoxy cholesterol was fed to 6 controls and 3 subjects with type III hyperlipoprotenemia, alpha-epoxy cholesterol in serum was found in chylomicron/chylomicron remnants (CM/RM) and endogenous (VLDL, LDL, and HDL) lipoproteins. In controls, a-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 hyperlipoprotenemia, 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 a-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 (CETP) is mediating the transfer. Thus, alpha-epoxy cholesterol in the diet is incorporated into 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 cooper 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.

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