[Modified LDL and atherosclerosis. Nature of modifications. Physicochemical and biological properties].
The role of plasma LDL in atherogenesis is now well established. Cholesteryl ester accumulation within macrophages leads to foam cell formation, an early atherosclerotic process. In vitro, foam cell formation scarcely ever occurs in the presence of native LDL. Modification of these lipoproteins is necessary for their binding to macrophage scavenger receptors. In vitro modifications reported have involved chemical reactions, physical mechanisms, enzymatic reactions, cellular interactions and association with macromolecules. In vivo, they can occur by glycation or desialylation, smoking or by hemodynamic interactions. Alterations of the physicochemical properties of LDL are induced by oxidation and include an increase in their density and their net electronegative charge, changes in lecithin composition, polyunsaturated fatty acid peroxidation of lipids and apolipoprotein B100 degradation. Apolipoprotein B100 fragmentation leads to an impairment of uptake through LDL receptors, while uptake through macrophage scavenger receptors is enhanced. Modified LDL have also other particularities such as cytotoxicity, chemotactism for circulating monocytes, inhibition of resident macrophage mobility, vasoconstriction, perturbation of the arachidonic acid cascade, involvement in haemostasis and immune mechanisms. Hypotheses concerning the role of modified LDL, in particular oxidized LDL, in atherogenesis open new therapeutic prospects.
Pech
M A
MA
Laboratoire de biochimie appliquée, faculté des sciences pharmaceutiques et biologiques, Châtenay-Malabry, France.
Myara
I
I
Vedie
B
B
Moatti
N
N
D000818:Animals; D001161:Arteriosclerosis / Q000097:blood*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006801:Humans; D008077:Lipoproteins, LDL / Q000737:chemistry* / Q000378:metabolism
D008077:Lipoproteins, LDL
LDL modifiées et athérosclérose. Nature des modifications. Propriétés physicochimiques et biologiques.