[Oxygen, phagocytic cells and atheroma].
Phagocytes (P), i.e. neutrophils, monocytes and macrophages, may be involved as well as reactive oxygen species (ROS) in the initiation and development of atherosclerosis. Evidences for this assumption are the following; P and ROS are both able to damage endothelial cells whose dysfunction is crucial in the etiology of atherosclerosis. ROS generated by endothelial cells, smooth muscle cells or mainly blood cells such as neutrophils but also monocytes platelets and erythrocytes, peroxide directly endothelial cell membranes. Damage to cell membranes can be induced by P that adhere to, and release on endothelial cells large amounts of proteolytic and lipolytic enzymes. ROS can also induce formation in the blood of lipoperoxides which are often included in LDL (low density lipoproteins). These modified LDL are cytotoxic, possess phospholipase A2 activity and are recognized by the LDL scavenger receptor which is on the monocyte-macrophage membrane. The modified LDL are also immunogenic inducing formation of autoantibodies directed against them and normal LDL. Modified LDL and LDL immune complexes can be ingested by monocytes leading to foam cells and ROS. The damaged endothelial cells have an increased permeability to macromolecules, synthetize chemotactic factors, decrease their prostacyclin production and favour the adherence of neutrophils and monocytes to their surface. All these factors could increase ROS production and lipid peroxidation amplifying intra and extra-cellular accumulation of lipoperoxides in vascular walls. The ability of ROS and P to damage endothelial cells, to induce lipid peroxidation and thus to be involved in atherosclerosis relies on in vitro experimental results.(ABSTRACT TRUNCATED AT 250 WORDS)
Hakim
J
J
Unité de recherches sur la Physiopathologie des réactions inflammatoires et des radicaux libres (U. 294 de l'INSERM) UER Xavier Bichat, Paris.
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D006801:Humans; D010100:Oxygen / Q000502:physiology*; D010586:Phagocytes / Q000502:physiology*; D051381:Rats
D010100:Oxygen
Oxygène, cellules phagocytaires et athérome.