Vascular biology of eicosanoids and atherogenesis.
Atherosclerosis is a chronic and progressive inflammatory vascular disease that is characterized by a complex interplay between some components of the bloodstream and the arterial wall. The lipid derivatives eicosanoids have been identified as important mediators that contribute to mechanisms of atherogenesis. Prostaglandins and thromboxane A2 are members of the eicosanoid family synthesized from arachidonic acid by the combined action of cyclooxygenases and prostaglandins and thromboxane A2 synthase. Thromboxane A2, a potent platelet activator and vasoconstrictor and prostacyclin, a platelet inhibitor and vasodilator, are the most important in the development of cardiovascular diseases. Several pro-atherogenic biological effects have also been attributed to isoprostanes, a class of eicosanoid isomers formed via a free radical-mediated oxidation of fatty acids esterified in membrane phospholipids. Both groups of lipids manifest their biological activities by binding to specific receptors in target cells. In this article, we will describe the biological roles of prostacyclin, thromboxane A2 and isoprostanes in atherogenesis and discuss the latest pharmacological studies assessing the therapeutic effects of drugs that specifically target their biosynthesis and/or biological activities on vascular inflammation and atherosclerotic lesion development.
Praticò
Domenico
D
Temple University, Department of Pharmacology, Philadelphia, PA 19140, USA. praticod@temple.edu
Dogné
Jean-Michel
JM
D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy* / Q000503:physiopathology; D002317:Cardiovascular Agents / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D016503:Drug Delivery Systems; D015777:Eicosanoids / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D028421:Isoprostanes / Q000378:metabolism; D013928:Thromboxane A2 / Q000378:metabolism
D002317:Cardiovascular Agents; D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D028421:Isoprostanes; D013928:Thromboxane A2; D011464:Epoprostenol