Evidence map›Paper›PMID 27496857›Full record

Trial reportCirculation2016

Oxidized Phospholipids on Lipoprotein(a) Elicit Arterial Wall Inflammation and an Inflammatory Monocyte Response in Humans.

Fleur M van der Valk, Siroon Bekkering, Jeffrey Kroon, Calvin Yeang, Jan Van den Bossche, Jaap D van Buul, Amir Ravandi, Aart J Nederveen, Hein J Verberne, Corey Scipione and 8 more

Registry-linked trialOpen access · bronzeAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Circulation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03700424 (The Use of Intravenous Trehalose to Reduce Vascular Inflammation in Acute Coronary Syndrome), which is not on this map. Cited by 330 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
330citing papers in PubMed, 5 pooled it
18.2field-weighted citation impact, top 1% 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.

NCT03700424 phase2unknown statusnot on this mapstarted 2020, after this paper: background citation

The Use of Intravenous Trehalose to Reduce Vascular Inflammation in Acute Coronary Syndrome

TypeinterventionalSponsorMashhad University of Medical SciencesRan2020 to 2022Enrolled15ConditionsAcute Coronary SyndromeArmsTrehalose, Normal saline
3 · Its place in the literature

Who cites it

330 citing papers in PubMed, 5 syntheses or guidelines pooled it, 625 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Oxidized Phospholipids and Calcific Aortic Valvular Disease.Journal of the American College of Cardiology · 2024
    Pooled it
  4. Pooled it
  5. Pooled it
  6. Trial
  7. Trial
  8. Review
  9. Association of lipoprotein(a) with ischemia-reperfusion injury in patients with ST-elevation myocardial infarction.Clinical research in cardiology : official journal of the German Cardiac Society · 2026
    Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. [EJNMMI research · 2026
    Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. Review

270 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 5 institutions in 3 countries.

Fleur M van der ValkFrom Department of Vascular Medicine (F.M.V.d.V., M.N., E.S.G.S.), Department of Molecular Cell Biology, Sanquin Research (J.K., J.D.v.B.), Experimental Vascular Biology, (J.v.d.B.), Department of Radiology (A.J.N.), and Department of Nuclear Medicine (H.J.V.), Academic Medical Center, Amsterdam, the Netherlands; Departments of Internal Medicine (S.B., L.A.B.J., M.G.N., N.P.R.) and Pharmacology-Toxicology (N.P.R.), Radboud UMC, Nijmegen, the Netherlands; Sulpizio Cardiovascular Center, Division of Cardiovascular Medicine (C.Y., S.T.) and Division of Endocrinology and Metabolism, Department of Medicine (J.L.W.), University California, San Diego, La Jolla; St. Boniface Hospital Research Centre, University of Manitoba, Winnipeg, Canada (A.R.); Department of Chemistry, Biochemistry and Pharmacology, University of Windsor, Windsor, Canada (C.S.); and Robarts Research Institute, Schulich School of Medicine, Western University, London, Canada (M.L.K.).
Siroon BekkeringFrom Department of Vascular Medicine (F.M.V.d.V., M.N., E.S.G.S.), Department of Molecular Cell Biology, Sanquin Research (J.K., J.D.v.B.), Experimental Vascular Biology, (J.v.d.B.), Department of Radiology (A.J.N.), and Department of Nuclear Medicine (H.J.V.), Academic Medical Center, Amsterdam, the Netherlands; Departments of Internal Medicine (S.B., L.A.B.J., M.G.N., N.P.R.) and Pharmacology-Toxicology (N.P.R.), Radboud UMC, Nijmegen, the Netherlands; Sulpizio Cardiovascular Center, Division of Cardiovascular Medicine (C.Y., S.T.) and Division of Endocrinology and Metabolism, Department of Medicine (J.L.W.), University California, San Diego, La Jolla; St. Boniface Hospital Research Centre, University of Manitoba, Winnipeg, Canada (A.R.); Department of Chemistry, Biochemistry and Pharmacology, University of Windsor, Windsor, Canada (C.S.); and Robarts Research Institute, Schulich School of Medicine, Western University, London, Canada (M.L.K.).
Jeffrey KroonFrom Department of Vascular Medicine (F.M.V.d.V., M.N., E.S.G.S.), Department of Molecular Cell Biology, Sanquin Research (J.K., J.D.v.B.), Experimental Vascular Biology, (J.v.d.B.), Department of Radiology (A.J.N.), and Department of Nuclear Medicine (H.J.V.), Academic Medical Center, Amsterdam, the Netherlands; Departments of Internal Medicine (S.B., L.A.B.J., M.G.N., N.P.R.) and Pharmacology-Toxicology (N.P.R.), Radboud UMC, Nijmegen, the Netherlands; Sulpizio Cardiovascular Center, Division of Cardiovascular Medicine (C.Y., S.T.) and Division of Endocrinology and Metabolism, Department of Medicine (J.L.W.), University California, San Diego, La Jolla; St. Boniface Hospital Research Centre, University of Manitoba, Winnipeg, Canada (A.R.); Department of Chemistry, Biochemistry and Pharmacology, University of Windsor, Windsor, Canada (C.S.); and Robarts Research Institute, Schulich School of Medicine, Western University, London, Canada (M.L.K.).
Calvin YeangFrom Department of Vascular Medicine (F.M.V.d.V., M.N., E.S.G.S.), Department of Molecular Cell Biology, Sanquin Research (J.K., J.D.v.B.), Experimental Vascular Biology, (J.v.d.B.), Department of Radiology (A.J.N.), and Department of Nuclear Medicine (H.J.V.), Academic Medical Center, Amsterdam, the Netherlands; Departments of Internal Medicine (S.B., L.A.B.J., M.G.N., N.P.R.) and Pharmacology-Toxicology (N.P.R.), Radboud UMC, Nijmegen, the Netherlands; Sulpizio Cardiovascular Center, Division of Cardiovascular Medicine (C.Y., S.T.) and Division of Endocrinology and Metabolism, Department of Medicine (J.L.W.), University California, San Diego, La Jolla; St. Boniface Hospital Research Centre, University of Manitoba, Winnipeg, Canada (A.R.); Department of Chemistry, Biochemistry and Pharmacology, University of Windsor, Windsor, Canada (C.S.); and Robarts Research Institute, Schulich School of Medicine, Western University, London, Canada (M.L.K.).
Jan Van den BosscheFrom Department of Vascular Medicine (F.M.V.d.V., M.N., E.S.G.S.), Department of Molecular Cell Biology, Sanquin Research (J.K., J.D.v.B.), Experimental Vascular Biology, (J.v.d.B.), Department of Radiology (A.J.N.), and Department of Nuclear Medicine (H.J.V.), Academic Medical Center, Amsterdam, the Netherlands; Departments of Internal Medicine (S.B., L.A.B.J., M.G.N., N.P.R.) and Pharmacology-Toxicology (N.P.R.), Radboud UMC, Nijmegen, the Netherlands; Sulpizio Cardiovascular Center, Division of Cardiovascular Medicine (C.Y., S.T.) and Division of Endocrinology and Metabolism, Department of Medicine (J.L.W.), University California, San Diego, La Jolla; St. Boniface Hospital Research Centre, University of Manitoba, Winnipeg, Canada (A.R.); Department of Chemistry, Biochemistry and Pharmacology, University of Windsor, Windsor, Canada (C.S.); and Robarts Research Institute, Schulich School of Medicine, Western University, London, Canada (M.L.K.).
Jaap D van BuulFrom Department of Vascular Medicine (F.M.V.d.V., M.N., E.S.G.S.), Department of Molecular Cell Biology, Sanquin Research (J.K., J.D.v.B.), Experimental Vascular Biology, (J.v.d.B.), Department of Radiology (A.J.N.), and Department of Nuclear Medicine (H.J.V.), Academic Medical Center, Amsterdam, the Netherlands; Departments of Internal Medicine (S.B., L.A.B.J., M.G.N., N.P.R.) and Pharmacology-Toxicology (N.P.R.), Radboud UMC, Nijmegen, the Netherlands; Sulpizio Cardiovascular Center, Division of Cardiovascular Medicine (C.Y., S.T.) and Division of Endocrinology and Metabolism, Department of Medicine (J.L.W.), University California, San Diego, La Jolla; St. Boniface Hospital Research Centre, University of Manitoba, Winnipeg, Canada (A.R.); Department of Chemistry, Biochemistry and Pharmacology, University of Windsor, Windsor, Canada (C.S.); and Robarts Research Institute, Schulich School of Medicine, Western University, London, Canada (M.L.K.).
Amir RavandiFrom Department of Vascular Medicine (F.M.V.d.V., M.N., E.S.G.S.), Department of Molecular Cell Biology, Sanquin Research (J.K., J.D.v.B.), Experimental Vascular Biology, (J.v.d.B.), Department of Radiology (A.J.N.), and Department of Nuclear Medicine (H.J.V.), Academic Medical Center, Amsterdam, the Netherlands; Departments of Internal Medicine (S.B., L.A.B.J., M.G.N., N.P.R.) and Pharmacology-Toxicology (N.P.R.), Radboud UMC, Nijmegen, the Netherlands; Sulpizio Cardiovascular Center, Division of Cardiovascular Medicine (C.Y., S.T.) and Division of Endocrinology and Metabolism, Department of Medicine (J.L.W.), University California, San Diego, La Jolla; St. Boniface Hospital Research Centre, University of Manitoba, Winnipeg, Canada (A.R.); Department of Chemistry, Biochemistry and Pharmacology, University of Windsor, Windsor, Canada (C.S.); and Robarts Research Institute, Schulich School of Medicine, Western University, London, Canada (M.L.K.).
Aart J NederveenFrom Department of Vascular Medicine (F.M.V.d.V., M.N., E.S.G.S.), Department of Molecular Cell Biology, Sanquin Research (J.K., J.D.v.B.), Experimental Vascular Biology, (J.v.d.B.), Department of Radiology (A.J.N.), and Department of Nuclear Medicine (H.J.V.), Academic Medical Center, Amsterdam, the Netherlands; Departments of Internal Medicine (S.B., L.A.B.J., M.G.N., N.P.R.) and Pharmacology-Toxicology (N.P.R.), Radboud UMC, Nijmegen, the Netherlands; Sulpizio Cardiovascular Center, Division of Cardiovascular Medicine (C.Y., S.T.) and Division of Endocrinology and Metabolism, Department of Medicine (J.L.W.), University California, San Diego, La Jolla; St. Boniface Hospital Research Centre, University of Manitoba, Winnipeg, Canada (A.R.); Department of Chemistry, Biochemistry and Pharmacology, University of Windsor, Windsor, Canada (C.S.); and Robarts Research Institute, Schulich School of Medicine, Western University, London, Canada (M.L.K.).
Hein J VerberneFrom Department of Vascular Medicine (F.M.V.d.V., M.N., E.S.G.S.), Department of Molecular Cell Biology, Sanquin Research (J.K., J.D.v.B.), Experimental Vascular Biology, (J.v.d.B.), Department of Radiology (A.J.N.), and Department of Nuclear Medicine (H.J.V.), Academic Medical Center, Amsterdam, the Netherlands; Departments of Internal Medicine (S.B., L.A.B.J., M.G.N., N.P.R.) and Pharmacology-Toxicology (N.P.R.), Radboud UMC, Nijmegen, the Netherlands; Sulpizio Cardiovascular Center, Division of Cardiovascular Medicine (C.Y., S.T.) and Division of Endocrinology and Metabolism, Department of Medicine (J.L.W.), University California, San Diego, La Jolla; St. Boniface Hospital Research Centre, University of Manitoba, Winnipeg, Canada (A.R.); Department of Chemistry, Biochemistry and Pharmacology, University of Windsor, Windsor, Canada (C.S.); and Robarts Research Institute, Schulich School of Medicine, Western University, London, Canada (M.L.K.).
Corey ScipioneFrom Department of Vascular Medicine (F.M.V.d.V., M.N., E.S.G.S.), Department of Molecular Cell Biology, Sanquin Research (J.K., J.D.v.B.), Experimental Vascular Biology, (J.v.d.B.), Department of Radiology (A.J.N.), and Department of Nuclear Medicine (H.J.V.), Academic Medical Center, Amsterdam, the Netherlands; Departments of Internal Medicine (S.B., L.A.B.J., M.G.N., N.P.R.) and Pharmacology-Toxicology (N.P.R.), Radboud UMC, Nijmegen, the Netherlands; Sulpizio Cardiovascular Center, Division of Cardiovascular Medicine (C.Y., S.T.) and Division of Endocrinology and Metabolism, Department of Medicine (J.L.W.), University California, San Diego, La Jolla; St. Boniface Hospital Research Centre, University of Manitoba, Winnipeg, Canada (A.R.); Department of Chemistry, Biochemistry and Pharmacology, University of Windsor, Windsor, Canada (C.S.); and Robarts Research Institute, Schulich School of Medicine, Western University, London, Canada (M.L.K.).
Max NieuwdorpFrom Department of Vascular Medicine (F.M.V.d.V., M.N., E.S.G.S.), Department of Molecular Cell Biology, Sanquin Research (J.K., J.D.v.B.), Experimental Vascular Biology, (J.v.d.B.), Department of Radiology (A.J.N.), and Department of Nuclear Medicine (H.J.V.), Academic Medical Center, Amsterdam, the Netherlands; Departments of Internal Medicine (S.B., L.A.B.J., M.G.N., N.P.R.) and Pharmacology-Toxicology (N.P.R.), Radboud UMC, Nijmegen, the Netherlands; Sulpizio Cardiovascular Center, Division of Cardiovascular Medicine (C.Y., S.T.) and Division of Endocrinology and Metabolism, Department of Medicine (J.L.W.), University California, San Diego, La Jolla; St. Boniface Hospital Research Centre, University of Manitoba, Winnipeg, Canada (A.R.); Department of Chemistry, Biochemistry and Pharmacology, University of Windsor, Windsor, Canada (C.S.); and Robarts Research Institute, Schulich School of Medicine, Western University, London, Canada (M.L.K.).
Leo A B JoostenFrom Department of Vascular Medicine (F.M.V.d.V., M.N., E.S.G.S.), Department of Molecular Cell Biology, Sanquin Research (J.K., J.D.v.B.), Experimental Vascular Biology, (J.v.d.B.), Department of Radiology (A.J.N.), and Department of Nuclear Medicine (H.J.V.), Academic Medical Center, Amsterdam, the Netherlands; Departments of Internal Medicine (S.B., L.A.B.J., M.G.N., N.P.R.) and Pharmacology-Toxicology (N.P.R.), Radboud UMC, Nijmegen, the Netherlands; Sulpizio Cardiovascular Center, Division of Cardiovascular Medicine (C.Y., S.T.) and Division of Endocrinology and Metabolism, Department of Medicine (J.L.W.), University California, San Diego, La Jolla; St. Boniface Hospital Research Centre, University of Manitoba, Winnipeg, Canada (A.R.); Department of Chemistry, Biochemistry and Pharmacology, University of Windsor, Windsor, Canada (C.S.); and Robarts Research Institute, Schulich School of Medicine, Western University, London, Canada (M.L.K.).
Mihai G NeteaFrom Department of Vascular Medicine (F.M.V.d.V., M.N., E.S.G.S.), Department of Molecular Cell Biology, Sanquin Research (J.K., J.D.v.B.), Experimental Vascular Biology, (J.v.d.B.), Department of Radiology (A.J.N.), and Department of Nuclear Medicine (H.J.V.), Academic Medical Center, Amsterdam, the Netherlands; Departments of Internal Medicine (S.B., L.A.B.J., M.G.N., N.P.R.) and Pharmacology-Toxicology (N.P.R.), Radboud UMC, Nijmegen, the Netherlands; Sulpizio Cardiovascular Center, Division of Cardiovascular Medicine (C.Y., S.T.) and Division of Endocrinology and Metabolism, Department of Medicine (J.L.W.), University California, San Diego, La Jolla; St. Boniface Hospital Research Centre, University of Manitoba, Winnipeg, Canada (A.R.); Department of Chemistry, Biochemistry and Pharmacology, University of Windsor, Windsor, Canada (C.S.); and Robarts Research Institute, Schulich School of Medicine, Western University, London, Canada (M.L.K.).
Marlys L KoschinskyFrom Department of Vascular Medicine (F.M.V.d.V., M.N., E.S.G.S.), Department of Molecular Cell Biology, Sanquin Research (J.K., J.D.v.B.), Experimental Vascular Biology, (J.v.d.B.), Department of Radiology (A.J.N.), and Department of Nuclear Medicine (H.J.V.), Academic Medical Center, Amsterdam, the Netherlands; Departments of Internal Medicine (S.B., L.A.B.J., M.G.N., N.P.R.) and Pharmacology-Toxicology (N.P.R.), Radboud UMC, Nijmegen, the Netherlands; Sulpizio Cardiovascular Center, Division of Cardiovascular Medicine (C.Y., S.T.) and Division of Endocrinology and Metabolism, Department of Medicine (J.L.W.), University California, San Diego, La Jolla; St. Boniface Hospital Research Centre, University of Manitoba, Winnipeg, Canada (A.R.); Department of Chemistry, Biochemistry and Pharmacology, University of Windsor, Windsor, Canada (C.S.); and Robarts Research Institute, Schulich School of Medicine, Western University, London, Canada (M.L.K.).
Joseph L WitztumFrom Department of Vascular Medicine (F.M.V.d.V., M.N., E.S.G.S.), Department of Molecular Cell Biology, Sanquin Research (J.K., J.D.v.B.), Experimental Vascular Biology, (J.v.d.B.), Department of Radiology (A.J.N.), and Department of Nuclear Medicine (H.J.V.), Academic Medical Center, Amsterdam, the Netherlands; Departments of Internal Medicine (S.B., L.A.B.J., M.G.N., N.P.R.) and Pharmacology-Toxicology (N.P.R.), Radboud UMC, Nijmegen, the Netherlands; Sulpizio Cardiovascular Center, Division of Cardiovascular Medicine (C.Y., S.T.) and Division of Endocrinology and Metabolism, Department of Medicine (J.L.W.), University California, San Diego, La Jolla; St. Boniface Hospital Research Centre, University of Manitoba, Winnipeg, Canada (A.R.); Department of Chemistry, Biochemistry and Pharmacology, University of Windsor, Windsor, Canada (C.S.); and Robarts Research Institute, Schulich School of Medicine, Western University, London, Canada (M.L.K.).
Sotirios TsimikasFrom Department of Vascular Medicine (F.M.V.d.V., M.N., E.S.G.S.), Department of Molecular Cell Biology, Sanquin Research (J.K., J.D.v.B.), Experimental Vascular Biology, (J.v.d.B.), Department of Radiology (A.J.N.), and Department of Nuclear Medicine (H.J.V.), Academic Medical Center, Amsterdam, the Netherlands; Departments of Internal Medicine (S.B., L.A.B.J., M.G.N., N.P.R.) and Pharmacology-Toxicology (N.P.R.), Radboud UMC, Nijmegen, the Netherlands; Sulpizio Cardiovascular Center, Division of Cardiovascular Medicine (C.Y., S.T.) and Division of Endocrinology and Metabolism, Department of Medicine (J.L.W.), University California, San Diego, La Jolla; St. Boniface Hospital Research Centre, University of Manitoba, Winnipeg, Canada (A.R.); Department of Chemistry, Biochemistry and Pharmacology, University of Windsor, Windsor, Canada (C.S.); and Robarts Research Institute, Schulich School of Medicine, Western University, London, Canada (M.L.K.).
Niels P RiksenFrom Department of Vascular Medicine (F.M.V.d.V., M.N., E.S.G.S.), Department of Molecular Cell Biology, Sanquin Research (J.K., J.D.v.B.), Experimental Vascular Biology, (J.v.d.B.), Department of Radiology (A.J.N.), and Department of Nuclear Medicine (H.J.V.), Academic Medical Center, Amsterdam, the Netherlands; Departments of Internal Medicine (S.B., L.A.B.J., M.G.N., N.P.R.) and Pharmacology-Toxicology (N.P.R.), Radboud UMC, Nijmegen, the Netherlands; Sulpizio Cardiovascular Center, Division of Cardiovascular Medicine (C.Y., S.T.) and Division of Endocrinology and Metabolism, Department of Medicine (J.L.W.), University California, San Diego, La Jolla; St. Boniface Hospital Research Centre, University of Manitoba, Winnipeg, Canada (A.R.); Department of Chemistry, Biochemistry and Pharmacology, University of Windsor, Windsor, Canada (C.S.); and Robarts Research Institute, Schulich School of Medicine, Western University, London, Canada (M.L.K.).
Erik S G StroesFrom Department of Vascular Medicine (F.M.V.d.V., M.N., E.S.G.S.), Department of Molecular Cell Biology, Sanquin Research (J.K., J.D.v.B.), Experimental Vascular Biology, (J.v.d.B.), Department of Radiology (A.J.N.), and Department of Nuclear Medicine (H.J.V.), Academic Medical Center, Amsterdam, the Netherlands; Departments of Internal Medicine (S.B., L.A.B.J., M.G.N., N.P.R.) and Pharmacology-Toxicology (N.P.R.), Radboud UMC, Nijmegen, the Netherlands; Sulpizio Cardiovascular Center, Division of Cardiovascular Medicine (C.Y., S.T.) and Division of Endocrinology and Metabolism, Department of Medicine (J.L.W.), University California, San Diego, La Jolla; St. Boniface Hospital Research Centre, University of Manitoba, Winnipeg, Canada (A.R.); Department of Chemistry, Biochemistry and Pharmacology, University of Windsor, Windsor, Canada (C.S.); and Robarts Research Institute, Schulich School of Medicine, Western University, London, Canada (M.L.K.). e.s.stroes@amc.uva.nl.
St. Boniface Hospital · CAUniversity of California, San Diego · USUniversity of Windsor · CARadboud University Medical Center · NLUniversity of Manitoba · CA

Funding

ROLE OF LIPOXYGENASES IN ATHEROGENESIS IN DIABETES MELLITUSP01HL055798 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI HEDRICK, CATHERINE C · 1995 to 2016
$28.4M
Transcriptional GenomicsP01HL088093 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WITZTUM, JOSEPH L. · 2008 to 2018
$26.4M
Shear Regulation of MicroRNA Transportomes and Targetomes in Vascular HomeostasisR01HL106579 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHIEN, SHU, SHYY, JOHN YJ · 2011 to 2022
$8.3M
Targeted CEU Imaging of Atherosclerosis and AngiogenesisR01HL078610 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI LINDNER, JONATHAN R · 2004 to 2022
$6.8M
Blood Cells in Hemostasis and ThrombosisT32HL086344 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GINSBERG, MARK HOWARD · 2008 to 2023
$4.4M
Oxidation-specific nanoparticles for imaging atherosclerosisR01HL119828 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TSIMIKAS, SOTIRIOS · 2013 to 2017
$2.0M
AIBP and Endothelial FunctionR01HL124174 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MILLER, YURY · 2015 to 2016
$1.0M
NHLBI NIH HHS P01 HL055798NHLBI NIH HHS P01 HL088093NHLBI NIH HHS R01 HL078610NHLBI NIH HHS R01 HL106579NHLBI NIH HHS R01 HL119828NHLBI NIH HHS R01 HL124174NHLBI NIH HHS T32 HL086344
6 · The paper itself

Abstract

backgroundElevated lipoprotein(a) [Lp(a)] is a prevalent, independent cardiovascular risk factor, but the underlying mechanisms responsible for its pathogenicity are poorly defined. Because Lp(a) is the prominent carrier of proinflammatory oxidized phospholipids (OxPLs), part of its atherothrombosis might be mediated through this pathway.

methodsIn vivo imaging techniques including magnetic resonance imaging, (18)F-fluorodeoxyglucose uptake positron emission tomography/computed tomography and single-photon emission computed tomography/computed tomography were used to measure subsequently atherosclerotic burden, arterial wall inflammation, and monocyte trafficking to the arterial wall. Ex vivo analysis of monocytes was performed with fluorescence-activated cell sorter analysis, inflammatory stimulation assays, and transendothelial migration assays. In vitro studies of the pathophysiology of Lp(a) on monocytes were performed with an in vitro model for trained immunity.

resultsWe show that subjects with elevated Lp(a) (108 mg/dL [50-195 mg/dL]; n=30) have increased arterial inflammation and enhanced peripheral blood mononuclear cells trafficking to the arterial wall compared with subjects with normal Lp(a) (7 mg/dL [2-28 mg/dL]; n=30). In addition, monocytes isolated from subjects with elevated Lp(a) remain in a long-lasting primed state, as evidenced by an increased capacity to transmigrate and produce proinflammatory cytokines on stimulation (n=15). In vitro studies show that Lp(a) contains OxPL and augments the proinflammatory response in monocytes derived from healthy control subjects (n=6). This effect was markedly attenuated by inactivating OxPL on Lp(a) or removing OxPL on apolipoprotein(a).

conclusionsThese findings demonstrate that Lp(a) induces monocyte trafficking to the arterial wall and mediates proinflammatory responses through its OxPL content. These findings provide a novel mechanism by which Lp(a) mediates cardiovascular disease. CLINICAL

trial registrationURL: http://www.trialregister.nl. Unique identifier: NTR5006 (VIPER Study).

Indexed as

AdultAgedAortaCell MovementCells, CulturedFemaleHumansInflammationInflammation MediatorsLeukocytes, MononuclearLipoprotein(a)MaleMiddle AgedPhospholipidsPositron Emission Tomography Computed TomographyInflammation MediatorsLipoprotein(a)Phospholipidsatherosclerosislipoproteinsmonocytes

Identifiers

PMID27496857
PMCPMC4995139
OpenAlexW2498232546

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Registered trials

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.