Oxidized phospholipids in control of inflammation and endothelial barrier

The levels of circulating oxidized phospholipids (OxPLs) become increased in chronic and acute pathologic conditions such as hyperlipidemia, atherosclerosis, increased intimamedia thickness in the patients with systemic Lupus erythematosus, vascular balloon injury, acute lung injury (ALI), and acute respiratory distress syndrome (ARDS). These pathologies are associated with inflammation and activation of endothelial cells. Depending on the biological context and the specific group of phospholipid oxidation products, OxPL may exhibit both proinflammatory and anti-inflammatory effects. This review will summarize the data showing a dual role of OxPL in modulation of chronic and acute inflammation as well as OxPL effects on pulmonary endothelial permeability. Recent reports show protective effects of OxPL in the models of endotoxin and ventilator-induced ALI and suggest a potential for using OxPL-derived cyclopenthenone-containing compounds with barrier-protective properties for drug design. These compounds may represent a new group of therapeutic agents for the treatment of lung syndromes associated with acute inflammation and lung vascular leak.