Prostanoid and isoprostanoid pathways in atherogenesis

Atherosclerosis is a chronic inflammatory disease of the vasculature that is influenced by multiple factors and involves a complex interplay between some components of the bloodstream and the arterial wall. Among different circulating factors implicated in atherogenesis there is a large group of bioactive lipids called prostanoids and isoprostanoids. Prostanoids are formed via the enzymatic oxidation of arachidonic acid, and the various sub-classes are generated by distinct enzymatic pathways. Isoprostanoids represent a class of prostanoid isomers formed via a free radical-mediated oxidation of fatty acids esterified in membrane phospholipids. Both groups of lipids manifest their biologic activities by binding to specific receptors in target cells. In recent years, a lot of research effort has been focused on these lipid mediators because of their active roles in cardiovascular physiology, and because their biosynthesis is severely altered in patients with atherosclerosis. This review article describes the biological roles that prostanoids, isoprostanoids and their receptors play in atherogenesis by integrating our current knowledge of basic cellular mechanisms with the results of experimental genetic and pharmacologic studies using modulators of these pathways.