Oxidized LDLs influence thrombotic response and cyclooxygenase 2.
Oxidative modification of low-density lipoproteins (LDLs) plays a key role in the development of atherosclerosis and the onset of coronary artery disease. LDL oxidation alters the antithrombotic balance of human endothelial cells inducing surface tissue factor (TF) pathway activity, which results in enhanced fibrin deposition. Fibrinolysis, which is strictly regulated by plasminogen activator inhibitor-1 (PAL-1) and tissue-type plasminogen activator (tPA). Is also dysregulated by LDL oxidation with a net increase in the inhibitory rate. Oxidized LDLs (oxLDLs) also affect many aspects of macrophage function linked to the inflammatory response of these cells, In particular, oxLDLs downregulate inducible cyclooxigenase (Cox-2) in human monocyte-derived macrophages exposed to bacterial lipopolysaccharide. This observation may support the hypothesis that, within atheromata, the transformation macrophages into foam cells results in the attenuation of the inflammatory response, thus contributing to the progression of athrogenesis. Among lipid constituents of oxLDLs, Ox-PAPC, a mixture of oxidized arachidonic acid-containing phospholipids, prevents Cox-2 expression, suggesting that it could be considered responsible for the biological activity of oxLDLs.
D001161:Arteriosclerosis / Q000150:complications; D001777:Blood Coagulation / Q000187:drug effects; D051546:Cyclooxygenase 2; D005487:Foam Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D013927:Thrombosis / Q000139:chemically induced* / Q000150:complications / Q000201:enzymology
D007527:Isoenzymes; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; C099252:oxidized low density lipoprotein; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases