Oxidized phospholipids as modulators of inflammation in atherosclerosis

Abstract

This review will summarize recent evidence demonstrating that biologically active phospholipid oxidation products modulate inflammatory reactions. Structural identification of new biologically active oxidized phospholipids and the finding that they can also be formed at inflammatory sites other than the atherosclerotic lesion have expanded the potential role of these compounds in inflammation beyond atherogenesis. Various signaling pathways are induced by oxidized phospholipids, leading to the expression of inflammatory genes by mechanisms that differ from those mediated by the classic inflammatory agonists tumor necrosis factor or lipopolysaccharide. Furthermore, oxidized phospholipids can bind to pattern recognition molecules and thus potently influence inflammation and immune responses during host defense. During inflammatory processes biologically active lipid oxidation products accumulate that modulate the inflammatory process and may determine the fate and outcome of the body's reaction in acute inflammation during host defense. Oxidized phospholipids may induce and propagate chronic inflammatory processes; however, evidence is accumulating that cells and tissues respond towards these oxidatively formed stress signals also by activation of anti-inflammatory, cytoprotective reactions.