The Good and Bad Faces of Oxidized Phospholipids: Friends or Foes of Vascular Endothelium?

A diverse group of bioactive lipids are generated from the oxidation of phospholipids during various pathological conditions such as lung injury, sepsis, and autoimmune diseases. An elevated level of circulating oxidized phospholipids with potent inflammatory activities has been recognized as a hallmark of various diseases including atherosclerosis. On the other hand, the oxidation of a principal membrane phospholipid 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PAPC) results in the formation of a heterogeneous mixture of full length and fragmented oxidized species with both beneficial and detrimental effects on pulmonary endothelium. Among these, the extensive studies from this research group have established that full length oxidized species present in oxidized PAPC (OxPAPC) have pronounced endothelial barrier protective and anti-inflammatory properties. This has been documented in various cellular and animal models of lung injury and inflammation using a wide range of chemical and mechanical stimuli. Moreover, OxPAPC stimulation of endothelial cells generates anti-inflammatory molecules such as lipoxin that mediate the recovery of inflamed lungs. This review briefly summarizes the current knowledge on OxPAPC-mediated positive regulation of endothelial barrier function and its potential as a promising therapeutic target for lung injury and inflammation. Practical Applications: This review briefly summarizes the current knowledge on OxPAPC-mediated positive regulation of endothelial barrier function and its potential as a promising therapeutic target for lung injury and inflammation. Products of phospholipid oxidation may exhibit disruptive or protective effects on vascular endothelium depending on the extent of oxidation. Full length oxidized phospholipids stimulated endothelial barrier recovery and resolution of acute lung injury or sepsis by triggering multiple mechanisms enhancing endothelial barrier properties and diminishing inflammation.