Phospholipid mediators in the vessel wall: involvement in atherosclerosis.
OBJECTIVE
This review provides a brief update on the involvement of major phospholipid mediators, with the emphasis on platelet-activating factor and its analogues generated upon the oxidation of lipoproteins in vascular pathology, including atherogenesis.


RESULTS
Phospholipid mediators are produced during inflammation by various enzymes, mostly from pre-existing membrane phospholipids, and trigger cellular signaling via G-coupled receptors. A short description of lysophosphatidic acid, lysophosphocholine and sphingosine-1 phosphate receptors and their actions is given, but attention is focused mainly on platelet-activating factor and its analogues. The majority of these mediators participate in leukocyte adhesiveness to the endothelium, leukocyte transmigration into the vessel wall and the subsequent formation of various chemokines leading to foam cell formation and smooth muscle cell proliferation and dedifferentiation. Platelet-activating factor and platelet-activating factor-like phospholipids are degraded in plasma by the lipoprotein-bound enzyme of myeloid origin, PAF-acetylhydrolase, also known as LDL-PLA2. Although the overexpression of PAF-acetylhydrolase shows marked anti-atherogenic properties in animal models, epidemiological data in the Caucasian population have demonstrated that its level might be a risk factor for cardiovascular disease. Recent genetic studies have shown, however, that the A379V polymorphism of this gene, responsible for slightly higher enzymatic activity, exerts a protective effect, probably by modifying the enzyme function towards a less atherogenic form.


CONCLUSIONS
Phospholipid-borne mediators are certainly key players in inflammation and thus in atherosclerosis. The generation of such biologically active molecules is possibly dependent on nutritional habits and the availability of antioxidants, including enzymes protective against oxidative damage, including PAF-acetylhydrolase.
Ninio
Ewa
E
INSERM U525, IFR14 Coeur Muscle Vaisseaux and Université P.M. Curie, Faculté de Médecine, Paris, France. ninio@chups.jussieu.fr
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism*; D001161:Arteriosclerosis / Q000201:enzymology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism / Q000502:physiology*; D010972:Platelet Activating Factor / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism
D010743:Phospholipids; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D054467:Phospholipases A2; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase