Evidence map›Paper›PMID 25966710›Full record

ArticleCirculation research2015

Receptor-Mediated Mechanism Controlling Tissue Levels of Bioactive Lipid Oxidation Products.

Young-Woong Kim, Valentin P Yakubenko, Xiaoxia Z West, Gabriel B Gugiu, Kutralanathan Renganathan, Sudipta Biswas, Detao Gao, John W Crabb, Robert G Salomon, Eugene A Podrez and 1 more

Open access · bronzeAbstract read
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In one paragraph

Article in Circulation research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.5field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
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  5. The OSE complotype and its clinical potential.Frontiers in immunology · 2022
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  11. Inhibition of integrin αThe Journal of biological chemistry · 2019
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  12. Amount of Mononuclear Phagocyte Infiltrate Does Not Predict Area of Experimental Choroidal Neovascularization (CNV).Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2018
    Article
  13. Article
  14. Article
  15. Article
  16. Biological and pathophysiological roles of end-products of DHA oxidation.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2017
    Review
  17. Context-Dependent Role of Oxidized Lipids and Lipoproteins in Inflammation.Trends in endocrinology and metabolism: TEM · 2017
    Review
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 1 institution in 1 country.

Young-Woong KimFrom the Department of Molecular Cardiology, Lerner Research Institute (Y.-W.K., V.P.Y., X.Z.W., S.B., D.G., E.A.P., T.V.B.) and Department of Ophthalmology, Cole Eye Institute (R.K., J.W.C.), Cleveland Clinic, OH; and Department of Chemistry, Case Western Reserve University, Cleveland, OH (G.B.G., R.K., R.G.S.).
Valentin P YakubenkoFrom the Department of Molecular Cardiology, Lerner Research Institute (Y.-W.K., V.P.Y., X.Z.W., S.B., D.G., E.A.P., T.V.B.) and Department of Ophthalmology, Cole Eye Institute (R.K., J.W.C.), Cleveland Clinic, OH; and Department of Chemistry, Case Western Reserve University, Cleveland, OH (G.B.G., R.K., R.G.S.).
Xiaoxia Z WestFrom the Department of Molecular Cardiology, Lerner Research Institute (Y.-W.K., V.P.Y., X.Z.W., S.B., D.G., E.A.P., T.V.B.) and Department of Ophthalmology, Cole Eye Institute (R.K., J.W.C.), Cleveland Clinic, OH; and Department of Chemistry, Case Western Reserve University, Cleveland, OH (G.B.G., R.K., R.G.S.).
Gabriel B GugiuFrom the Department of Molecular Cardiology, Lerner Research Institute (Y.-W.K., V.P.Y., X.Z.W., S.B., D.G., E.A.P., T.V.B.) and Department of Ophthalmology, Cole Eye Institute (R.K., J.W.C.), Cleveland Clinic, OH; and Department of Chemistry, Case Western Reserve University, Cleveland, OH (G.B.G., R.K., R.G.S.).
Kutralanathan RenganathanFrom the Department of Molecular Cardiology, Lerner Research Institute (Y.-W.K., V.P.Y., X.Z.W., S.B., D.G., E.A.P., T.V.B.) and Department of Ophthalmology, Cole Eye Institute (R.K., J.W.C.), Cleveland Clinic, OH; and Department of Chemistry, Case Western Reserve University, Cleveland, OH (G.B.G., R.K., R.G.S.).
Sudipta BiswasFrom the Department of Molecular Cardiology, Lerner Research Institute (Y.-W.K., V.P.Y., X.Z.W., S.B., D.G., E.A.P., T.V.B.) and Department of Ophthalmology, Cole Eye Institute (R.K., J.W.C.), Cleveland Clinic, OH; and Department of Chemistry, Case Western Reserve University, Cleveland, OH (G.B.G., R.K., R.G.S.).
Detao GaoFrom the Department of Molecular Cardiology, Lerner Research Institute (Y.-W.K., V.P.Y., X.Z.W., S.B., D.G., E.A.P., T.V.B.) and Department of Ophthalmology, Cole Eye Institute (R.K., J.W.C.), Cleveland Clinic, OH; and Department of Chemistry, Case Western Reserve University, Cleveland, OH (G.B.G., R.K., R.G.S.).
John W CrabbFrom the Department of Molecular Cardiology, Lerner Research Institute (Y.-W.K., V.P.Y., X.Z.W., S.B., D.G., E.A.P., T.V.B.) and Department of Ophthalmology, Cole Eye Institute (R.K., J.W.C.), Cleveland Clinic, OH; and Department of Chemistry, Case Western Reserve University, Cleveland, OH (G.B.G., R.K., R.G.S.).
Robert G SalomonFrom the Department of Molecular Cardiology, Lerner Research Institute (Y.-W.K., V.P.Y., X.Z.W., S.B., D.G., E.A.P., T.V.B.) and Department of Ophthalmology, Cole Eye Institute (R.K., J.W.C.), Cleveland Clinic, OH; and Department of Chemistry, Case Western Reserve University, Cleveland, OH (G.B.G., R.K., R.G.S.).
Eugene A PodrezFrom the Department of Molecular Cardiology, Lerner Research Institute (Y.-W.K., V.P.Y., X.Z.W., S.B., D.G., E.A.P., T.V.B.) and Department of Ophthalmology, Cole Eye Institute (R.K., J.W.C.), Cleveland Clinic, OH; and Department of Chemistry, Case Western Reserve University, Cleveland, OH (G.B.G., R.K., R.G.S.).
Tatiana V ByzovaFrom the Department of Molecular Cardiology, Lerner Research Institute (Y.-W.K., V.P.Y., X.Z.W., S.B., D.G., E.A.P., T.V.B.) and Department of Ophthalmology, Cole Eye Institute (R.K., J.W.C.), Cleveland Clinic, OH; and Department of Chemistry, Case Western Reserve University, Cleveland, OH (G.B.G., R.K., R.G.S.). byzovat@ccf.org.
Cleveland Clinic Lerner College of Medicine · US

Funding

Regulation of Integrins in Neovasculature DevelopmentR01HL071625 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI BYZOVA, TATIANA V · 2003 to 2021
$7.3M
Preprostaglandin Endoperoxides (supplement)R01GM021249 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI SALOMON, ROBERT GERD · 1985 to 2014
$5.2M
Pathophysiological Activities of Oxidized PhospholipidsR01HL077213 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI PODREZ, EUGENE A · 2005 to 2018
$4.5M
REACTIVE INTERMEDIATES OF OXIDATIVE LIPID FRAGMENTATIONR01EY016813 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI SALOMON, ROBERT GERD · 2006 to 2018
$3.9M
The role of β2 integrins in macrophage retention and egress during inflammationR01DK102020 · NIDDK · EAST TENNESSEE STATE UNIVERSITY · PI YAKUBENKO, VALENTIN P · 2014 to 2017
$1.2M
Carboxyethylpyrrole-Ethanolamine Phospholipids as AMD BiomarkersR21EY025388 · NEI · CLEVELAND CLINIC LERNER COM-CWRU · PI CRABB, JOHN W · 2015 to 2016
$436k
Role of beta2 integrins in macrophage retention and egress during inflammationR56DK102020 · NIDDK · CLEVELAND CLINIC LERNER COM-CWRU · PI YAKUBENKO, VALENTIN P · 2014 to 2014
$79k
NEI NIH HHS EY016813NEI NIH HHS R01 EY016813NEI NIH HHS R21 EY025388NHLBI NIH HHS HL071625NHLBI NIH HHS HL077213NHLBI NIH HHS R01 HL071625NHLBI NIH HHS R01 HL077213NIDDK NIH HHS DK102020NIDDK NIH HHS R01 DK102020NIDDK NIH HHS R56 DK102020NIGMS NIH HHS GM021249NIGMS NIH HHS R01 GM021249
6 · The paper itself

Abstract

rationaleOxidative stress is an important contributing factor in several human pathologies ranging from atherosclerosis to cancer progression; however, the mechanisms underlying tissue protection from oxidation products are poorly understood. Oxidation of membrane phospholipids, containing the polyunsaturated fatty acid docosahexaenoic acid, results in the accumulation of an end product, 2-(ω-carboxyethyl)pyrrole (CEP), which was shown to have proangiogenic and proinflammatory functions. Although CEP is continuously accumulated during chronic processes, such as tumor progression and atherosclerosis, its level during wound healing return to normal when the wound is healed, suggesting the existence of a specific clearance mechanism.

objectiveTo identify the cellular and molecular mechanism for CEP clearance. METHODS AND

resultsHere, we show that macrophages are able to bind, scavenge, and metabolize carboxyethylpyrrole derivatives of proteins but not structurally similar ethylpyrrole derivatives, demonstrating the high specificity of the process. F4/80(hi) and M2-skewed macrophages are much more efficient at CEP binding and scavenging compared with F4/80(lo) and M1-skewed macrophages. Depletion of macrophages leads to increased CEP accumulation in vivo. CEP binding and clearance are dependent on 2 receptors expressed by macrophages, CD36 and toll-like receptor 2. Although knockout of each individual receptor results in diminished CEP clearance, the lack of both receptors almost completely abrogates macrophages' ability to scavenge CEP derivatives of proteins.

conclusionsOur study demonstrates the mechanisms of recognition, scavenging, and clearance of pathophysiologically active products of lipid oxidation in vivo, thereby contributing to tissue protection against products of oxidative stress.

Indexed as

Oxidative StressAnimalsAntigens, DifferentiationApolipoproteins EAtherosclerosisCD36 AntigensDisease Models, AnimalHEK293 CellsHumansLipoproteins, LDLMacrophages, PeritonealMelanoma, ExperimentalMice, Inbred C57BLMice, KnockoutNeovascularization, PhysiologicPhenotype2-(omega-carboxyethyl)pyrroleAntigens, DifferentiationApolipoproteins ECD36 AntigensLipoproteins, LDLmonocyte-macrophage differentiation antigenoxidized low density lipoproteinPyrrolesTlr2 protein, mouseToll-Like Receptor 2angiogenesis inducing agentsantigens, CD36macrophagestoll-like receptor 2wound healing

Identifiers

PMID25966710
PMCPMC4522201
OpenAlexW2171782802

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.