Evidence of modified LDL in the plasma of hypercholesterolemic WHHL rabbits injected with aqueous extracts of cigarette smoke

Cigarette smoking is a major risk factor for atherosclerosis, and oxidative modification of low density lipoprotein (LDL) is a key event in the develo pment of atherosclerosis. The aim of the present study was to determine whe ther modified LDL would be formed in the plasma of Watanabe heritable hyper lipidemic (WHHL) rabbits injected with nicotine-free cigarette smoke extrac ts (CSE). In order to assess this, cigarette smoke-modified LDL (CS-LDL) wa s prepared by incubation of rabbit native LDL (N-LDL) with CSE for 24 h. Th e oxidative modification in CS-LDL was well established by the reduced rati o between two LDL subfractions (LDL2/LDL3) separated by anion-exchange HPLC , together with the fast migration in the anodic direction in agarose gel e lectrophoresis and the increased lipid peroxide levels. Very similar modifi cation was noted with mildly oxidatively modified LBL prepared by incubatio n of N-LDL with 5 mu M CuCl2 for 1 h. When WHHL rabbits (n = 4) intravenous ly received a single injection of CSE, the ratio of LDL2/LDL3 was markedly reduced compared with the control rabbits (n = 4) while total cholesterol l evels in the plasma gradually decreased until 24 h after the injection. The se results suggest that oxidatively modified LDL, probably like CS-LDL. is produced in the plasma of WHHL rabbits injected with CSE. (C) 2000 Elsevier Science B.V. All rights reserved.