Evidence map›Paper›PMID 37293282›Full record

ArticleFrontiers in cardiovascular medicine2023

Lipoprotein(a) induces caspase-1 activation and IL-1 signaling in human macrophages.

Martina B Lorey, Amer Youssef, Lauri Äikäs, Matthew Borrelli, Martin Hermansson, Julia M Assini, Aapeli Kemppainen, Hanna Ruhanen, Maija Ruuth, Sampsa Matikainen and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in cardiovascular medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

5 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Lipoprotein(a) and cardiovascular disease.The Biochemical journal · 2024
    Review
  5. Article
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

15 authors at 3 institutions in 2 countries.

Martina B LoreyAtherosclerosis Research Laboratory, Wihuri Research Institute, Helsinki, Finland.
Amer YoussefRobarts Research Institute, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, Canada.
Lauri ÄikäsAtherosclerosis Research Laboratory, Wihuri Research Institute, Helsinki, Finland.
Matthew BorrelliDepartment of Physiology & Pharmacology, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, Canada.
Martin HermanssonAtherosclerosis Research Laboratory, Wihuri Research Institute, Helsinki, Finland.
Julia M AssiniRobarts Research Institute, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, Canada.
Aapeli KemppainenAtherosclerosis Research Laboratory, Wihuri Research Institute, Helsinki, Finland.
Hanna RuhanenMolecular and Integrative Biosciences, Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland.
Maija RuuthAtherosclerosis Research Laboratory, Wihuri Research Institute, Helsinki, Finland.
Sampsa MatikainenHelsinki Rheumatic Disease and Inflammation Research Group, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Petri T KovanenAtherosclerosis Research Laboratory, Wihuri Research Institute, Helsinki, Finland.
Reijo KäkeläMolecular and Integrative Biosciences, Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland.
Michael B BoffaRobarts Research Institute, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, Canada.
Marlys L KoschinskyRobarts Research Institute, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, Canada.
Katariina ÖörniAtherosclerosis Research Laboratory, Wihuri Research Institute, Helsinki, Finland.
Wihuri Research Institute · FIWestern University · CAUniversity of Helsinki · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Lipoprotein(a) (Lp(a)) is an LDL-like particle with an additional apolipoprotein (apo)(a) covalently attached. Elevated levels of circulating Lp(a) are a risk factor for atherosclerosis. A proinflammatory role for Lp(a) has been proposed, but its molecular details are incompletely defined. Methods and results: To explore the effect of Lp(a) on human macrophages we performed RNA sequencing on THP-1 macrophages treated with Lp(a) or recombinant apo(a), which showed that especially Lp(a) induces potent inflammatory responses. Thus, we stimulated THP-1 macrophages with serum containing various Lp(a) levels to investigate their correlations with cytokines highlighted by the RNAseq, showing significant correlations with caspase-1 activity and secretion of IL-1β and IL-18. We further isolated both Lp(a) and LDL particles from three donors and then compared their atheroinflammatory potentials together with recombinant apo(a) in primary and THP-1 derived macrophages. Compared with LDL, Lp(a) induced a robust and dose-dependent caspase-1 activation and release of IL-1β and IL-18 in both macrophage types. Recombinant apo(a) strongly induced caspase-1 activation and IL-1β release in THP-1 macrophages but yielded weak responses in primary macrophages. Structural analysis of these particles revealed that the Lp(a) proteome was enriched in proteins associated with complement activation and coagulation, and its lipidome was relatively deficient in polyunsaturated fatty acids and had a high n-6/n-3 ratio promoting inflammation. Discussion: Our data show that Lp(a) particles induce the expression of inflammatory genes, and Lp(a) and to a lesser extent apo(a) induce caspase-1 activation and IL-1 signaling. Major differences in the molecular profiles between Lp(a) and LDL contribute to Lp(a) being more atheroinflammatory.

Indexed as

apolipoproteinsatherosclerosisatherosclerotic cardiovascular diseasecaspase-1inflammationinterleukin-1 familylipoprotein(a)

Identifiers

PMID37293282
PMCPMC10244518
OpenAlexW4377942915

What OpenQuestion holds

Textmetadata
LicenceCC BY
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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 OpenQuestion graph.