Lipid mediators in the regulation of endothelial barriers.

Lipid mediators play a critical role in the development and resolution of vascular endothelial barrier dysfunction caused by various pathologic interventions. The accumulation of excess lipids directly impairs endothelial cell (EC) barrier function that is known to contribute to the development of atherosclerosis and metabolic disorders such as obesity and diabetes as well as chronic inflammation in the vascular endothelium. Certain products of phospholipid oxidation (OxPL) such as fragmented phospholipids generated during oxidative and nitrosative stress show pro-inflammatory potential and cause endothelial barrier dysfunction. In turn, other OxPL products enhance basal EC barrier and exhibit potent barrier-protective effects in pathologic settings of acute vascular leak caused by pro-inflammatory mediators, barrier disruptive agonists and pathologic mechanical stimulation. These beneficial effects were further confirmed in rodent models of lung injury and inflammation. The bioactive oxidized lipid molecules may serve as important therapeutic prototype molecules for future treatment of acute lung injury syndromes associated with endothelial barrier dysfunction and inflammation. This review will summarize recent studies of biological effects exhibited by various groups of lipid mediators with a focus on the role of oxidized phospholipids in control of vascular endothelial barrier, agonist induced EC permeability, inflammation, and barrier recovery related to clinical settings of acute lung injury and inflammatory vascular leak.