Vascular Barrier Protective Properties of Bioactive Components of Oxidized Phospholipids Released During Acute Injury Conditions
regain vascular integrity and to prevent edema formation. However, mediators that control restoration of endothelial barrier function are largely unknown. JHU researchers have discovered that oxidized products of cell membrane phospholipids that accumulate at sites of inflammation and tissue damage are potent regulators of endothelial barrier function. Moreover, bioactive oxidized phospholipids induce approximately two-fold increase in recovery of pulmonary EC barrier properties compromised by edemagenic agents such as thrombin. JHU researchers have identified specific components of oxidized phospholipids with barrier protective properties, which will allow structure-based drug design and may reveal new therapeutic strategies for treatments of acute lung injury syndromes and other diseases associated with vascular leakage. Description (Set) Proposed Use (Set) Based on our studies, we propose a role for oxidized phospholipids in resolution of acute inflammation involving vascular leakage. Excessive accumulation of specific bioactive oxidized phospholipids is associated with early stages of acute lung injury characterized by high levels of oxidative stress and may compromise EC barrier function thus contributing to edema formation. However, at later phases, diminished oxidative stress in the areas of tissue injury leads to the formation of oxygenated phospholipids to the levels that would enhance EC barrier function, which would represent a feedback mechanism leading to EC barrier recovery. This protective effect can be further potentiated by sphingosine 1-phosphate generated by activated platelets, which acts synergistically with oxidized phospholipids.Inventor(s): Garcia, Joe, G.N.
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