ArticleTranslational research : the journal of laboratory and clinical medicine2013
Fragmented oxidation products define barrier disruptive endothelial cell response to OxPAPC.
Article in Translational research : the journal of laboratory and clinical medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 68 citations in OpenAlex.
- Post‑translational modifications in atherosclerosis: Roles, mechanisms and therapeutic potential (Review).International journal of molecular medicine · 2026Review
- Ferroptosis in Vascular Diseases: A Mechanistic and Immunological Perspective on Therapeutic Targeting.Antioxidants (Basel, Switzerland) · 2026Review
- Modification of the dermal matrix by senescence associated lipids and its functional consequence.Redox biology · 2026Article
- Oxidized phosphatidylcholines activate NOX1-mediated oxidative stress response and shift glucose metabolism in cardiac cells.American journal of physiology. Cell physiology · 2025Article
- Amphipathic Helical Peptide L37pA Protects against Lung Vascular Endothelial Dysfunction Caused by Truncated Oxidized Phospholipids via Antagonism with CD36 Receptor.American journal of respiratory cell and molecular biology · 2024Article
- Truncated oxidized phospholipids exacerbate endothelial dysfunction and lung injury caused by bacterial pathogens.Cellular signalling · 2023Article
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- Scavenger receptor BI attenuates oxidized phospholipid-induced pulmonary inflammation.Toxicology and applied pharmacology · 2023Article
- The Levels of Oxidized Phospholipids in High-Density Lipoprotein During the Course of Sepsis and Their Prognostic Value.Frontiers in immunology · 2022Article
- Chronic and Binge Alcohol Ingestion Increases Truncated Oxidized Phosphatidylcholines in Mice Lungs Due to Increased Oxidative Stress.Frontiers in physiology · 2022Article
- A highly conserved host lipase deacylates oxidized phospholipids and ameliorates acute lung injury in mice.eLife · 2021Article
- Oxidized Phospholipids in Control of Endothelial Barrier Function: Mechanisms and Implication in Lung Injury.Frontiers in endocrinology · 2021Review
- Dooming Phagocyte Responses: Inflammatory Effects of Endogenous Oxidized Phospholipids.Frontiers in endocrinology · 2021Review
- Synergistic Effect of WTC-Particulate Matter and Lysophosphatidic Acid Exposure and the Role of RAGE: In-Vitro and Translational Assessment.International journal of environmental research and public health · 2020Article
- Review
- Contrasting effects of stored allogeneic red blood cells and their supernatants on permeability and inflammatory responses in human pulmonary endothelial cells.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- Mechanosensitive Rap1 activation promotes barrier function of lung vascular endothelium under cyclic stretch.Molecular biology of the cell · 2019Article
- Article
- Elevated truncated oxidized phospholipids as a factor exacerbating ALI in the aging lungs.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- A novel role for NUPR1 in the keratinocyte stress response to UV oxidized phospholipids.Redox biology · 2019Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Excessive concentrations of oxidized phospholipids (OxPL), the products of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphatidylcholine (PAPC) oxidation have been detected in atherosclerosis, septic inflammation, and acute lung injury (ALI) and have been shown to induce vascular barrier dysfunction. In contrast, oxidized PAPC (OxPAPC) at low concentrations exhibit potent barrier protective effects. The nature of such biphasic effects remains unclear. We tested the hypothesis that barrier-disruptive effects of high OxPAPC doses on endothelial cell (EC) monolayer are defined by fragmented products of PAPC oxidation (lysophosphatidyl choline [lyso-PC], 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-phosphatidylcholine [POVPC], 1-palmitoyl-2-glutaroyl-sn-glycero-phosphatidylcholine [PGPC]), whereas barrier enhancing effects are mediated by full length oxidated PAPC products and may be reproduced by single compounds contained in the OxPAPC such as 1-palmitoyl-2-(5,6-epoxyisoprostane E2)-sn-glycero-3-phosphatidyl choline (PEIPC). All 3 fragmented OxPAPC products increased EC permeability in a dose-dependent manner, whereas PEIPC decreased it and reversed barrier disruptive effects of lyso-PC, POVPC, and PGPC monitored by measurements of transendothelial electrical resistance. Immunofluorescence staining and western blot analysis showed that PGPC mimicked the cytoskeletal remodeling and tyrosine phosphorylation of adherens junction (AJ) protein vascular endothelial (VE)-cadherin leading to EC barrier dysfunction induced by high OxPAPC concentrations. Barrier-disruptive effects of PGPC were abrogated by reactive oxygen species (ROS) inhibitor, N-acetyl cysteine, or Src kinase inhibitor, PP-2. The results of this study show that barrier disruptive effects of fragmented OxPAPC constituents (lyso-PC, POVPC, PGPC) are balanced by barrier enhancing effects of full length oxygenated products (PEIPC). These data strongly suggest that barrier disruptive effects of OxPAPC at higher concentrations are dictated by predominant effects of fragmented phospholipids such as PGPC, which promote ROS-dependent activation of Src kinase and VE-cadherin phosphorylation at Tyr(658) and Tyr(731) leading to disruption of endothelial cell AJs.
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