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Cholesteryl ester accumulation in macrophages incubated with low density lipoprotein pretreated with cigarette smoke extract

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)
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Although cigarette smoking is one of the major risk factors for atherosclerosis and coronary heart disease, the precise mechanisms of its adverse effects have not been fully elucidated. We incubated low density lipoprotein (LDL) with cigarette smoke (CS) extract and examined the incorporation of the lipoprotein by macrophages in vitro. When incubated with macrophages, LDL pretreated with CS extract (100 micrograms/ml) stimulated cholesteryl (/sup 14/C)oleate synthesis approximately equal to 12.5-fold that with unmodified LDL and transformed macrophages to cells rich in lipid droplets positively stained with oil red O. Enhancement in cholesteryl ester synthesis was dependent on the concentration of CS-modified LDL and exhibited saturation kinetics. When subjected to electrophoreses, CS-modified LDL migrated to a more anionic position than did unmodified LDL and showed extensive fragmentation of apolipoprotein B. This LDL modification depended upon the incubation time and concentration of the CS extract. Superoxide dismutase inhibited modification of LDL by 52%, suggesting that superoxide anion is, at least in part, involved. These results suggest that CS extract alters LDL into a form recognized and incorporated by macrophages. Such modification if it occurs in vivo, could explain the increased incidence of atherosclerosis and coronary heart disease in smokers.
Research Organization:
Kyoto Univ. Faculty of Medicine (Japan)
OSTI ID:
7191905
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 85:7; ISSN PNASA
Country of Publication:
United States
Language:
English

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Related Subjects

550201* -- Biochemistry-- Tracer Techniques
550901 -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AEROSOLS
ANIMAL CELLS
ANIMALS
ARTERIOSCLEROSIS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL ACCUMULATION
BIOLOGICAL EFFECTS
BIOSYNTHESIS
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CARDIOVASCULAR DISEASES
CHOLESTEROL
COLLOIDS
CONNECTIVE TISSUE CELLS
DISEASES
DISPERSIONS
ELECTROPHORESIS
ENZYMES
ESTERS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LIPIDS
LIPOPROTEINS
MACROPHAGES
MAMMALS
MICE
MONOCARBOXYLIC ACIDS
OLEIC ACID
ORGANIC ACIDS
ORGANIC COMPOUNDS
OXIDOREDUCTASES
PHAGOCYTES
PROTEINS
REACTION KINETICS
RESIDUES
RODENTS
SMOKES
SOLS
SOMATIC CELLS
STEROIDS
STEROLS
SUPEROXIDE DISMUTASE
SYNTHESIS
TOBACCO SMOKES
TRACER TECHNIQUES
VASCULAR DISEASES
VERTEBRATES