ABSTRACT
The vascular endothelium plays a critical role in maintenance of normal lung function. Perturbation of vascular endothelial cells (ECs) results in barrier dysfunction (1,2), a hallmark of vascular disorders including adult respiratory distress syndrome (ARDS), sepsis, tumor metastasis, and atherosclerosis (3-7). A variety of inflammatory mediators and reactive oxygen species (H2O2, superoxide anion, hydroxyl radical, nitric oxide, peroxynitrite, and oxidized LDL) alter EC barrier function, which has been implicated in the pathogenesis of vascular disorders (8-10). Earlier studies suggest that oxidant stress alters EC high-energy compounds, glutathione levels, and intracellular free Ca2+ (11,12); however, the mechanisms of oxidant-induced EC barrier dysfunction leading to vascular disorders are not well understood (13). It is hypothesized that oxidant-mediated alterations in edemogenic protein kinases and phosphatases regulate EC barrier function via direct modulation of lipid-derived second messengers. In this study, we have investigated the effect of oxidants in the modulation of phospholipases A2, C, and D in vascular endothelial cells and possible implication in vascular disorders.
