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Extracts of human atherosclerotic lesions modify LDL inducing enhanced macrophage uptake

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:5327906
;

Both an LDL-like fraction isolated from human aortic plaques and LDL incubated with cultured aortic endothelial or smooth muscle cells have been shown to be internalized by macrophages in vitro in an unregulated fashion leading to foam cell formation. Lipid peroxidation induced by free radicals released from cells was shown to be responsible for cell-modified LDL. The authors incubated LDL with a supernatant fraction of leached, i.e. non-homogenized, extracts of aortic plaques for one hour at 37/sup 0/C, to determine whether extracellular components present in arteries were also capable of modifying LDL. Extract-treated LDL showed the following changes relative to untreated LDL: 1) increased electrophretic mobility, 2) altered pattern of B-100 on SDS-PAGE, i.e. presence of a doublet with higher M/sub r/ than B-100, and 3) enhanced uptake by cultured mouse peritoneal macrophages as measured by increased degradation of /sup 125/I-LDL, and increased stimulation of cholesterol esterification using /sup 14/C-oleate. Extracts from homogenized plaques and grossly normal intima induced similar changes. The modification was tissue specific in that extracts of arteries but not of liver, muscle or skin modified LDL. Protease degradation of LDL during incubation was probably not responsible since inhibitors did not prevent modification. It is possible that products of lipid peroxidation present in extracellular lipid of arteries may propagate free radicals or be incorporated into LDL, leading to modifications similar to those found in cell-modified LDL.

Research Organization:
Cleveland Clinic Foundation, OH
OSTI ID:
5327906
Report Number(s):
CONF-8604222-
Journal Information:
Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:3; ISSN FEPRA
Country of Publication:
United States
Language:
English

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Related Subjects

550901* -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
ARTERIES
ARTERIOSCLEROSIS
BETA DECAY RADIOISOTOPES
BLOOD VESSELS
BODY
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CARDIOVASCULAR DISEASES
CARDIOVASCULAR SYSTEM
CELL CULTURES
CHEMICAL REACTIONS
CHOLESTEROL
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DISEASES
ELECTRON CAPTURE RADIOISOTOPES
ENDOTHELIUM
ESTERIFICATION
HYDROXY COMPOUNDS
IN VITRO
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
LIPIDS
LIPOPROTEINS
MACROPHAGES
MAMMALS
METABOLISM
MICE
MONOCARBOXYLIC ACIDS
MUSCLES
NUCLEI
ODD-EVEN NUCLEI
OLEIC ACID
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PATHOGENESIS
PHAGOCYTES
PROTEINS
RADIOISOTOPES
RODENTS
SOMATIC CELLS
STEROIDS
STEROLS
TISSUES
TRACER TECHNIQUES
VASCULAR DISEASES
VERTEBRATES