Evidence map›Paper›PMID 38269588›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2024

Diacylglycerols and Lysophosphatidic Acid, Enriched on Lipoprotein(a), Contribute to Monocyte Inflammation.

Kim E Dzobo, Arjen J Cupido, Barend M Mol, Lotte C A Stiekema, Miranda Versloot, Maaike Winkelmeijer, Jorge Peter, Anne-Marije Pennekamp, Stefan R Havik, Frédéric M Vaz and 9 more

Open access · hybridAbstract read
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
10.8field-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.

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

37 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.

  1. Oxidized Phospholipids and Calcific Aortic Valvular Disease.Journal of the American College of Cardiology · 2024
    Pooled it
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  20. Frontiers in cardiovascular medicine · 2026
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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

19 authors at 7 institutions in 4 countries.

Kim E DzoboDepartments of Experimental Vascular Medicine (K.E.D., M.V., M.W., J.P., A.-M.P., S.R.H., J.H.M.L., A.K.G., J.K.), Amsterdam University Medical Center (UMC), University of Amsterdam, Amsterdam Cardiovascular Sciences, the Netherlands.ORCID 0000-0003-4867-818X
Arjen J CupidoVascular Medicine (A.J.C., L.C.A.S., E.S.G.S.), Amsterdam University Medical Center (UMC), University of Amsterdam, Amsterdam Cardiovascular Sciences, the Netherlands.ORCID 0000-0003-3300-8124
Barend M MolDepartment of Vascular Surgery, University Medical Centre Utrecht, the Netherlands (B.M.M., D.P.V.d.K.).ORCID 0009-0009-3714-5514
Lotte C A StiekemaVascular Medicine (A.J.C., L.C.A.S., E.S.G.S.), Amsterdam University Medical Center (UMC), University of Amsterdam, Amsterdam Cardiovascular Sciences, the Netherlands.
Miranda VerslootDepartments of Experimental Vascular Medicine (K.E.D., M.V., M.W., J.P., A.-M.P., S.R.H., J.H.M.L., A.K.G., J.K.), Amsterdam University Medical Center (UMC), University of Amsterdam, Amsterdam Cardiovascular Sciences, the Netherlands.
Maaike WinkelmeijerDepartments of Experimental Vascular Medicine (K.E.D., M.V., M.W., J.P., A.-M.P., S.R.H., J.H.M.L., A.K.G., J.K.), Amsterdam University Medical Center (UMC), University of Amsterdam, Amsterdam Cardiovascular Sciences, the Netherlands.ORCID 0000-0002-1342-9338
Jorge PeterDepartments of Experimental Vascular Medicine (K.E.D., M.V., M.W., J.P., A.-M.P., S.R.H., J.H.M.L., A.K.G., J.K.), Amsterdam University Medical Center (UMC), University of Amsterdam, Amsterdam Cardiovascular Sciences, the Netherlands.ORCID 0000-0002-1117-4458
Anne-Marije PennekampDepartments of Experimental Vascular Medicine (K.E.D., M.V., M.W., J.P., A.-M.P., S.R.H., J.H.M.L., A.K.G., J.K.), Amsterdam University Medical Center (UMC), University of Amsterdam, Amsterdam Cardiovascular Sciences, the Netherlands.ORCID 0009-0009-4820-3986
Stefan R HavikDepartments of Experimental Vascular Medicine (K.E.D., M.V., M.W., J.P., A.-M.P., S.R.H., J.H.M.L., A.K.G., J.K.), Amsterdam University Medical Center (UMC), University of Amsterdam, Amsterdam Cardiovascular Sciences, the Netherlands.
Frédéric M VazCore Facility Metabolomics (F.M.V., M.v.W.), Amsterdam UMC, University of Amsterdam, the Netherlands.ORCID 0000-0002-9048-1041
Michel van WeeghelCore Facility Metabolomics (F.M.V., M.v.W.), Amsterdam UMC, University of Amsterdam, the Netherlands.ORCID 0000-0002-4916-2866
Koen H M PrangeDepartment of Medical Biochemistry, Amsterdam Infection and Immunity (K.H.M.P., M.P.J.d.W.), Amsterdam UMC, University of Amsterdam, the Netherlands.ORCID 0000-0002-9835-1735
Johannes H M LevelsDepartments of Experimental Vascular Medicine (K.E.D., M.V., M.W., J.P., A.-M.P., S.R.H., J.H.M.L., A.K.G., J.K.), Amsterdam University Medical Center (UMC), University of Amsterdam, Amsterdam Cardiovascular Sciences, the Netherlands.ORCID 0000-0002-8946-8819
Menno P J de WintherDepartment of Medical Biochemistry, Amsterdam Infection and Immunity (K.H.M.P., M.P.J.d.W.), Amsterdam UMC, University of Amsterdam, the Netherlands.ORCID 0000-0002-4038-6636
Sotirios TsimikasDivision of Cardiovascular Medicine, Sulpizio Cardiovascular Center, University of California San Diego, La Jolla (S.T.).ORCID 0000-0001-9834-9494
Albert K GroenDepartments of Experimental Vascular Medicine (K.E.D., M.V., M.W., J.P., A.-M.P., S.R.H., J.H.M.L., A.K.G., J.K.), Amsterdam University Medical Center (UMC), University of Amsterdam, Amsterdam Cardiovascular Sciences, the Netherlands.ORCID 0000-0002-9942-1854
Erik S G StroesVascular Medicine (A.J.C., L.C.A.S., E.S.G.S.), Amsterdam University Medical Center (UMC), University of Amsterdam, Amsterdam Cardiovascular Sciences, the Netherlands.ORCID 0000-0001-9555-6260
Dominique P V de KleijnDepartment of Vascular Surgery, University Medical Centre Utrecht, the Netherlands (B.M.M., D.P.V.d.K.).ORCID 0000-0003-2714-2140
Jeffrey KroonDepartments of Experimental Vascular Medicine (K.E.D., M.V., M.W., J.P., A.-M.P., S.R.H., J.H.M.L., A.K.G., J.K.), Amsterdam University Medical Center (UMC), University of Amsterdam, Amsterdam Cardiovascular Sciences, the Netherlands.ORCID 0000-0001-9983-6614
Amsterdam University Medical Centers · NLUniversity Medical Center Utrecht · NLAmsterdam Neuroscience · NLAmsterdam UMC Location Vrije Universiteit Amsterdam · NLGGD Amsterdam · NLUniversity of California San Diego · USVIB-KU Leuven Center for Cancer Biology · BE

Funding

Translating Lp(a) biology to clinical applicationsR01HL159156 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SOTIRIOS TSIMIKAS · 2022 to 2026
$3.3M
Aspirin, Lp(a) and Primary Prevention of Cardiovascular EventsR01HL170224 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SOTIRIOS TSIMIKAS · 2023 to 2026
$3.0M
European Research CouncilNHLBI NIH HHS R01 HL159156NHLBI NIH HHS R01 HL170224
6 · The paper itself

Abstract

backgroundOxidized phospholipids play a key role in the atherogenic potential of lipoprotein(a) (Lp[a]); however, Lp(a) is a complex particle that warrants research into additional proinflammatory mediators. We hypothesized that additional Lp(a)-associated lipids contribute to the atherogenicity of Lp(a).

methodsUntargeted lipidomics was performed on plasma and isolated lipoprotein fractions. The atherogenicity of the observed Lp(a)-associated lipids was tested ex vivo in primary human monocytes by RNA sequencing, ELISA, Western blot, and transendothelial migratory assays. Using immunofluorescence staining and single-cell RNA sequencing, the phenotype of macrophages was investigated in human atherosclerotic lesions.

resultsCompared with healthy individuals with low/normal Lp(a) levels (median, 7 mg/dL [18 nmol/L]; n=13), individuals with elevated Lp(a) levels (median, 87 mg/dL [218 nmol/L]; n=12) demonstrated an increase in lipid species, particularly diacylglycerols (DGs) and lysophosphatidic acid (LPA). DG and the LPA precursor lysophosphatidylcholine were enriched in the Lp(a) fraction. Ex vivo stimulation with DG(40:6) demonstrated a significant upregulation in proinflammatory pathways related to leukocyte migration, chemotaxis, NF-κB (nuclear factor kappa B) signaling, and cytokine production. Functional assessment showed a dose-dependent increase in the secretion of IL (interleukin)-6, IL-8, and IL-1β after DG(40:6) and DG(38:4) stimulation, which was, in part, mediated via the NLRP3 (NOD [nucleotide-binding oligomerization domain]-like receptor family pyrin domain containing 3) inflammasome. Conversely, LPA-stimulated monocytes did not exhibit an inflammatory phenotype. Furthermore, activation of monocytes by DGs and LPA increased their transendothelial migratory capacity. Human atherosclerotic plaques from patients with high Lp(a) levels demonstrated colocalization of Lp(a) with M1 macrophages, and an enrichment of CD68

conclusionsLp(a)-associated DGs and LPA have a potential role in Lp(a)-induced monocyte inflammation by increasing cytokine secretion and monocyte transendothelial migration. This DG-induced inflammation is, in part, NLRP3 inflammasome dependent.

Indexed as

LysophospholipidsMonocytesNLR Family, Pyrin Domain-Containing 3 ProteinDiglyceridesHumansInflammasomesInflammationInterleukin-1betaInterleukin-6Lipoprotein(a)NF-kappa BDiglyceridesInflammasomesInterleukin-1betaInterleukin-6Lipoprotein(a)LPA protein, humanlysophosphatidic acidLysophospholipidsNF-kappa BNLR Family, Pyrin Domain-Containing 3 Proteindiglyceridesinflammationlipidomicslipoprotein(a)monocytes

Identifiers

PMID38269588
PMCPMC10880937
OpenAlexW4391229570

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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 Socratic graph.