Oxidized Phospholipids in Control of Endothelial Barrier Function: Mechanisms and Implication in Lung Injury

Earlier studies investigating the pathogenesis of chronic vascular inflammation associated with atherosclerosis described pro-inflammatory and vascular barrier disruptive effects of lipid oxidation products accumulated in the sites of vascular lesion and atherosclerotic plaque. However, accumulating...

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Auteurs principaux:	Pratap Karki, Konstantin G. Birukov
Format:	article
Langue:	EN
Publié:	Frontiers Media S.A. 2021
Sujets:	oxidized phospholipids OxPAPC endothelial barrier inflammation lung injury Rho GTPases Diseases of the endocrine glands. Clinical endocrinology RC648-665
Accès en ligne:	https://doaj.org/article/5384cfc7956a408c813b4eb0d325d6bc
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spelling	oai:doaj.org-article:5384cfc7956a408c813b4eb0d325d6bc2021-11-30T12:00:48ZOxidized Phospholipids in Control of Endothelial Barrier Function: Mechanisms and Implication in Lung Injury1664-239210.3389/fendo.2021.794437https://doaj.org/article/5384cfc7956a408c813b4eb0d325d6bc2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fendo.2021.794437/fullhttps://doaj.org/toc/1664-2392Earlier studies investigating the pathogenesis of chronic vascular inflammation associated with atherosclerosis described pro-inflammatory and vascular barrier disruptive effects of lipid oxidation products accumulated in the sites of vascular lesion and atherosclerotic plaque. However, accumulating evidence including studies from our group suggests potent barrier protective and anti-inflammatory properties of certain oxidized phospholipids (OxPLs) in the lung vascular endothelium. Among these OxPLs, oxidized 1-palmitoyl-2-arachdonyl-sn-glycero-3-phosphocholine (OxPAPC) causes sustained enhancement of lung endothelial cell (EC) basal barrier properties and protects against vascular permeability induced by a wide variety of agonists ranging from bacterial pathogens and their cell wall components, endotoxins, thrombin, mechanical insults, and inflammatory cytokines. On the other hand, truncated OxPLs cause acute endothelial barrier disruption and potentiate inflammation. It appears that multiple signaling mechanisms triggering cytoskeletal remodeling are involved in OxPLs-mediated regulation of EC barrier. The promising vascular barrier protective and anti-inflammatory properties exhibited by OxPAPC and its particular components that have been established in the cellular and animal models of sepsis and acute lung injury has prompted consideration of OxPAPC as a prototype therapeutic molecule. In this review, we will summarize signaling and cytoskeletal mechanisms involved in OxPLs-mediated damage, rescue, and restoration of endothelial barrier in various pathophysiological settings and discuss a future potential of OxPAPC in treating lung disorders associated with endothelial barrier dysfunction.Pratap KarkiKonstantin G. BirukovFrontiers Media S.A.articleoxidized phospholipidsOxPAPCendothelial barrierinflammationlung injuryRho GTPasesDiseases of the endocrine glands. Clinical endocrinologyRC648-665ENFrontiers in Endocrinology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	oxidized phospholipids OxPAPC endothelial barrier inflammation lung injury Rho GTPases Diseases of the endocrine glands. Clinical endocrinology RC648-665
spellingShingle	oxidized phospholipids OxPAPC endothelial barrier inflammation lung injury Rho GTPases Diseases of the endocrine glands. Clinical endocrinology RC648-665 Pratap Karki Konstantin G. Birukov Oxidized Phospholipids in Control of Endothelial Barrier Function: Mechanisms and Implication in Lung Injury
description	Earlier studies investigating the pathogenesis of chronic vascular inflammation associated with atherosclerosis described pro-inflammatory and vascular barrier disruptive effects of lipid oxidation products accumulated in the sites of vascular lesion and atherosclerotic plaque. However, accumulating evidence including studies from our group suggests potent barrier protective and anti-inflammatory properties of certain oxidized phospholipids (OxPLs) in the lung vascular endothelium. Among these OxPLs, oxidized 1-palmitoyl-2-arachdonyl-sn-glycero-3-phosphocholine (OxPAPC) causes sustained enhancement of lung endothelial cell (EC) basal barrier properties and protects against vascular permeability induced by a wide variety of agonists ranging from bacterial pathogens and their cell wall components, endotoxins, thrombin, mechanical insults, and inflammatory cytokines. On the other hand, truncated OxPLs cause acute endothelial barrier disruption and potentiate inflammation. It appears that multiple signaling mechanisms triggering cytoskeletal remodeling are involved in OxPLs-mediated regulation of EC barrier. The promising vascular barrier protective and anti-inflammatory properties exhibited by OxPAPC and its particular components that have been established in the cellular and animal models of sepsis and acute lung injury has prompted consideration of OxPAPC as a prototype therapeutic molecule. In this review, we will summarize signaling and cytoskeletal mechanisms involved in OxPLs-mediated damage, rescue, and restoration of endothelial barrier in various pathophysiological settings and discuss a future potential of OxPAPC in treating lung disorders associated with endothelial barrier dysfunction.
format	article
author	Pratap Karki Konstantin G. Birukov
author_facet	Pratap Karki Konstantin G. Birukov
author_sort	Pratap Karki
title	Oxidized Phospholipids in Control of Endothelial Barrier Function: Mechanisms and Implication in Lung Injury
title_short	Oxidized Phospholipids in Control of Endothelial Barrier Function: Mechanisms and Implication in Lung Injury
title_full	Oxidized Phospholipids in Control of Endothelial Barrier Function: Mechanisms and Implication in Lung Injury
title_fullStr	Oxidized Phospholipids in Control of Endothelial Barrier Function: Mechanisms and Implication in Lung Injury
title_full_unstemmed	Oxidized Phospholipids in Control of Endothelial Barrier Function: Mechanisms and Implication in Lung Injury
title_sort	oxidized phospholipids in control of endothelial barrier function: mechanisms and implication in lung injury
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/5384cfc7956a408c813b4eb0d325d6bc
work_keys_str_mv	AT pratapkarki oxidizedphospholipidsincontrolofendothelialbarrierfunctionmechanismsandimplicationinlunginjury AT konstantingbirukov oxidizedphospholipidsincontrolofendothelialbarrierfunctionmechanismsandimplicationinlunginjury
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Oxidized Phospholipids in Control of Endothelial Barrier Function: Mechanisms and Implication in Lung Injury

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