Oxidants in cigarette smoke extract modify low-density lipoprotein in the plasma and facilitate atherogenesis in the aorta of Watanabe heritable hyperlipidemic rabbits.
Epidemiological studies have shown that cigarette smoking is a major cause of atherosclerosis. Oxidants as well as nicotine in cigarette smoke have been implicated in atherogenesis. To clarify the mechanism involved, we examined the chronic effects of nicotine and nicotine-free cigarette smoke extracts (CSE) on oxidative modification of low-density lipoprotein (LDL) in the plasma of Watanabe heritable hyperlipidemic rabbits and atherogenesis in the aorta. CSE was prepared by bubbling the gas phase of smoke (1 ml/three cigarettes) into phosphate buffer saline, and 3 ml of this CSE was injected daily into the ear vein of the rabbit for five months. The rabbits treated with CSE showed an increase in lipid peroxide levels, estimated as thiobarbituric acid reactive substances (TBARS), with a corresponding decrease in vitamin E levels in the plasma. They also showed enhanced oxidative modification of LDL, assessed by anion-exchange HPLC, incorporation into macrophages and measurement of TBARS. These events could be efficiently prevented by administering vitamin E (150 mg/kg/day, p.o.). Nicotine alone (0.5 mg/kg/day, s.c.) led to a temporary increase in the plasma triglyceride level. At the end of the experiment, CSE but not nicotine had caused progression of atherosclerotic lesions together with accumulation of cholesteryl ester in the thoracic aorta, while vitamin E had significantly prevented such atheromatous formation. These results indicate that oxidants in CSE can promote the development of atherosclerosis through oxidative modification of plasma LDL, particularly in hypercholesterolemia, and offer evidence for increased vitamin E utilization in smokers.
Yamaguchi
Y
Y
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Mukogawa Women's University, 11-68, Koshien Kyuban-cho, Nishinomiya 663-8179, Japan. yusan@mwu.mukogawa-u.ac.jp
Matsuno
S
S
Kagota
S
S
Haginaka
J
J
Kunitomo
M
M
D000818:Animals; D001018:Aortic Diseases / Q000209:etiology*; D001161:Arteriosclerosis / Q000209:etiology*; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D005260:Female; D006949:Hyperlipidemias / Q000150:complications / Q000235:genetics*; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood / Q000187:drug effects* / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D016877:Oxidants / Q000494:pharmacology*; D010947:Plants, Toxic; D011817:Rabbits; D012906:Smoke; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014026:Nicotiana; D014810:Vitamin E / Q000097:blood
D002788:Cholesterol Esters; D008055:Lipids; D008077:Lipoproteins, LDL; D016877:Oxidants; D012906:Smoke; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E