MetadataShow full item record
AbstractCirculating and cell membrane phospholipids undergo oxidation caused by enzymatic and non-enzymatic mechanisms. As a result, a diverse group of bioactive oxidized phospholipids generated in these conditions have both beneficial and harmful effects on the human body. Increased production of oxidized phospholipid products with deleterious effects is linked to the pathogenesis of various cardiopulmonary disorders such as atherosclerosis, thrombosis, acute lung injury (ALI), and inflammation. It has been determined that the contrasting biological effects of lipid oxidation products are governed by their structural variations. For example, full-length products of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine oxidation (OxPAPC) have prominent endothelial barrier protective and anti-inflammatory activities while most of the truncated oxidized phospholipids induce vascular leak and exacerbate inflammation. The extensive studies from our group and other groups have demonstrated a strong potential of OxPAPC in mitigating a wide range of agonist-induced lung injuries and inflammation in pulmonary endothelial cell culture and rodent models of ALI. Concurrently, elevated levels of truncated oxidized phospholipids are present in aged mice lungs that potentiate the inflammatory agents-induced lung injury. On the other hand, increased levels of full length OxPAPC products accelerate ALI recovery by facilitating production of anti-inflammatory lipid mediator, lipoxin A4, and other molecules with anti-inflammatory properties. These findings suggest that OxPAPC-assisted lipid program switch may be a promising therapeutic strategy for treatment of acute inflammatory syndromes. In this review, we will summarize the vascular-protective and deleterious aspects of oxidized phospholipids and discuss their therapeutic potential including engineering of stable analogs of oxidized phospholipids with improved anti-inflammatory and barrier-protective properties.
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85084030766&doi=10.3390%2fcells9040981&partnerID=40&md5=be667354d9a6548778e72f3b360ccb0a; http://hdl.handle.net/10713/12709
- Anti-Inflammatory Effects of OxPAPC Involve Endothelial Cell-Mediated Generation of LXA4.
- Authors: Ke Y, Zebda N, Oskolkova O, Afonyushkin T, Berdyshev E, Tian Y, Meng F, Sarich N, Bochkov VN, Wang JM, Birukova AA, Birukov KG
- Issue date: 2017 Jul 21
- Oxidized Phospholipids in Control of Endothelial Barrier Function: Mechanisms and Implication in Lung Injury.
- Authors: Karki P, Birukov KG
- Issue date: 2021
- Thermodynamic and kinetic investigations of the release of oxidized phospholipids from lipid membranes and its effect on vascular integrity.
- Authors: Heffern CT, Pocivavsek L, Birukova AA, Moldobaeva N, Bochkov VN, Lee KY, Birukov KG
- Issue date: 2013 Oct-Nov
- Oxidized phospholipids protect against lung injury and endothelial barrier dysfunction caused by heat-inactivated Staphylococcus aureus.
- Authors: Meliton AY, Meng F, Tian Y, Sarich N, Mutlu GM, Birukova AA, Birukov KG
- Issue date: 2015 Mar 15
- Elevated truncated oxidized phospholipids as a factor exacerbating ALI in the aging lungs.
- Authors: Ke Y, Karki P, Kim J, Son S, Berdyshev E, Bochkov VN, Birukova AA, Birukov KG
- Issue date: 2019 Mar