Evidence map›Paper›PMID 35455968›Full record

ArticleCells2022

Anti-β2-GPI Antibodies Induce Endothelial Cell Expression of Tissue Factor by LRP6 Signal Transduction Pathway Involving Lipid Rafts.

Gloria Riitano, Antonella Capozzi, Serena Recalchi, Daniela Caissutti, Agostina Longo, Vincenzo Mattei, Fabrizio Conti, Roberta Misasi, Tina Garofalo, Maurizio Sorice and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
2.0field-weighted citation impact, top 12% 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

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.

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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

11 authors at 1 institution in 1 country.

Gloria RiitanoDepartment of Experimental Medicine, "Sapienza" University of Rome, 00161 Rome, Italy.
Antonella CapozziDepartment of Experimental Medicine, "Sapienza" University of Rome, 00161 Rome, Italy.
Serena RecalchiDepartment of Experimental Medicine, "Sapienza" University of Rome, 00161 Rome, Italy.
Daniela CaissuttiDepartment of Experimental Medicine, "Sapienza" University of Rome, 00161 Rome, Italy.
Agostina LongoDepartment of Experimental Medicine, "Sapienza" University of Rome, 00161 Rome, Italy.
Vincenzo MatteiDepartment of Experimental Medicine, "Sapienza" University of Rome, 00161 Rome, Italy.ORCID 0000-0003-4677-088X
Fabrizio ContiRheumatology Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, "Sapienza" University of Rome, 00161 Rome, Italy.
Roberta MisasiDepartment of Experimental Medicine, "Sapienza" University of Rome, 00161 Rome, Italy.
Tina GarofaloDepartment of Experimental Medicine, "Sapienza" University of Rome, 00161 Rome, Italy.ORCID 0000-0003-0645-2510
Maurizio SoriceDepartment of Experimental Medicine, "Sapienza" University of Rome, 00161 Rome, Italy.
Valeria ManganelliDepartment of Experimental Medicine, "Sapienza" University of Rome, 00161 Rome, Italy.
Sapienza University of Rome · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In this study we analyzed whether anti-β2-GPI antibodies from patients with APS induce the endothelial cell expression of Tissue Factor (TF) by a LRP6 signal transduction pathway involving lipid rafts. HUVEC were stimulated with affinity purified anti-β2-GPI antibodies. Both LRP6 and β-catenin phosphorylation, as well as TF expression, were evaluated by western blot. Results demonstrated that triggering with affinity purified anti-β2-GPI antibodies induced LRP6 phosphorylation with consequent β-catenin activation, leading to TF expression on the cell surface. Interestingly, the lipid rafts affecting agent methyl-β-cyclodextrin as well as the LRP6 inhibitor Dickkopf 1 (DKK1) partially reduced the anti-β2-GPI antibodies effect, indicating that the anti-β2-GPI effects on TF expression may depend on a signalling transduction pathway involving both lipid rafts and LRP6. An interaction between β2-GPI, LRP6 and PAR-2 within these microdomains was demonstrated by gradient fractionation and coimmunoprecipitation experiments. Thus, anti-β2-GPI antibodies react with their target antigen likely associated to LRP6 and PAR-2 within plasma membrane lipid rafts of the endothelial cell. Anti-β2-GPI binding triggers β-catenin phosphorylation, leading to a procoagulant phenotype characterized by TF expression. These findings deal with a novel signal transduction pathway which provides new insight in the APS pathogenesis, improving the knowledge of valuable therapeutic target(s).

Indexed as

Antiphospholipid SyndromeLow Density Lipoprotein Receptor-Related Protein-6Membrane MicrodomainsSignal TransductionThromboplastinbeta 2-Glycoprotein Ibeta CateninEndothelial CellsHumansbeta 2-Glycoprotein Ibeta CateninF3 protein, humanLow Density Lipoprotein Receptor-Related Protein-6LRP6 protein, humanThromboplastinantiphospholipid syndromeLRP-6signal transductionTissue Factorβ2-GPI-glycoprotein I

Identifiers

PMID35455968
PMCPMC9025633
OpenAlexW4223493705

What OpenQuestion holds

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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.