Scavenger receptor-independent stimulation of cholesterol esterification in macrophages by low density lipoprotein extracted from human aortic intima.
- 1 May 1992
- journal article
- abstracts
- Published by Wolters Kluwer Health in Arteriosclerosis and Thrombosis: A Journal of Vascular Biology
- Vol. 12 (5), 608-625
- https://doi.org/10.1161/01.atv.12.5.608
Abstract
There is a growing body of evidence that suggests that modification of low density lipoprotein (LDL) in the artery wall may contribute to atherogenesis. A number of physiologically plausible modifications have been studied in vitro, including oxidation, aggregation, formation of complexes with glycosaminoglycans, and generation of LDL-immune complexes. Several studies of the properties of LDL extracted from the aortic intima have been published, but these indicate disagreement about both the nature and the extent of modification of LDL in the artery wall. The objectives of the present study were to determine the nature and extent of modification of LDL extracted from both normal and diseased human aortic intimas and to correlate this with the rate of LDL uptake in cultured cells. Analyses were performed on LDLs isolated from aortic intimas obtained at autopsy or at the time of organ harvest from 33 subjects. LDL from normal intima showed no clear evidence of oxidation but had slightly increased electrophoretic mobility compared with native plasma LDL, whereas LDL from plaques or fatty streaks exhibited variable but usually modest signs of oxidative change. Aortic LDL was more rapidly degraded by cultured macrophages than was plasma LDL and resulted in a greater stimulation of cholesterol esterification. The degree of stimulation of cholesterol esterification was correlated with the extent of modification of LDL as reflected by the degree of apolipoprotein B fragmentation. However, in all aortic LDLs the extent of oxidative change, as assessed by electrophoretic mobility or other physical parameters, was less than that required for scavenger receptor-mediated uptake. In all cases where sufficient amounts of LDL were recovered to permit degradation experiments, the uptake of aortic LDL was nonsaturable and could not be inhibited by polyinosinic acid or acetylated LDL. Chromatography on Sepharose CL-4B showed that most LDLs isolated from plaque contained a fraction that eluted in the void volume, and the size of this void peak correlated well with the stimulation of cholesterol esterification. Electron microscopy showed that the high-molecular-weight fraction contained several different types of aggregates. Some appeared to be clusters of LDL-size particles, but large vesicular structures with numerous adherent LDL particles as well as lipid droplets were also identified. These results indicate that the accelerated uptake by macrophages of LDL isolated from the arterial intima can largely be attributed to phagocytosis of LDL-containing aggregates.(ABSTRACT TRUNCATED AT 400 WORDS)Keywords
This publication has 49 references indexed in Scilit:
- Cytochemical localization of β-lipoproteins and their components in successive stages of hyperlipidemic atherogenesis of rabbit aortaAtherosclerosis, 1989
- Beyond CholesterolNew England Journal of Medicine, 1989
- Lack of effect of probucol on atheroma formation in cholesterol-fed rabbits kept at comparable plasma cholesterol levelsAtherosclerosis, 1989
- Changes in high-density lipoprotein subfraction distribution and increased cholesteryl ester transfer after probucolThe American Journal of Cardiology, 1988
- Low density lipoprotein retention by aortic tissue☆Contribution of extracellular matrixAtherosclerosis, 1986
- Lipoproteins containing apolipoprotein A-I extracted from human aortasBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1982
- The binding of total low density lipoproteins in human arterial intima affected and unaffected by atherosclerosisAtherosclerosis, 1979
- Apo B concentration in the normal human aortaBiochemical and Biophysical Research Communications, 1978
- Preparation of tissue fluid of the vessel wall and determination of its lipoproteinsAtherosclerosis, 1974
- The metabolism of very low density lipoprotein proteins I. Preliminary in vitro and in vivo observationsBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1972