Evidence map›Paper›PMID 38732244›Full record

ArticleInternational journal of molecular sciences2024

Investigation of Strategies to Block Downstream Effectors of AT1R-Mediated Signalling to Prevent Aneurysm Formation in Marfan Syndrome.

Irene Valdivia Callejon, Lucia Buccioli, Jarl Bastianen, Jolien Schippers, Aline Verstraeten, Ilse Luyckx, Silke Peeters, A H Jan Danser, Roland R J Van Kimmenade, Josephina Meester and 1 more

Abstract read
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In one paragraph

Article in International journal of molecular sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. 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

11 authors.

Irene Valdivia CallejonCentre of Medical Genetics, Antwerp University Hospital, University of Antwerp, 2650 Antwerp, Belgium.ORCID 0000-0002-2723-9957
Lucia BuccioliCentre of Medical Genetics, Antwerp University Hospital, University of Antwerp, 2650 Antwerp, Belgium.
Jarl BastianenCentre of Medical Genetics, Antwerp University Hospital, University of Antwerp, 2650 Antwerp, Belgium.
Jolien SchippersCentre of Medical Genetics, Antwerp University Hospital, University of Antwerp, 2650 Antwerp, Belgium.
Aline VerstraetenCentre of Medical Genetics, Antwerp University Hospital, University of Antwerp, 2650 Antwerp, Belgium.
Ilse LuyckxCentre of Medical Genetics, Antwerp University Hospital, University of Antwerp, 2650 Antwerp, Belgium.ORCID 0000-0002-9668-0535
Silke PeetersCentre of Medical Genetics, Antwerp University Hospital, University of Antwerp, 2650 Antwerp, Belgium.ORCID 0000-0001-6705-6429
A H Jan DanserDepartment of Internal Medicine, Erasmus Medical Center, 3015 GD Rotterdam, The Netherlands.ORCID 0000-0002-5052-3585
Roland R J Van KimmenadeDepartment of Cardiology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
Josephina MeesterCentre of Medical Genetics, Antwerp University Hospital, University of Antwerp, 2650 Antwerp, Belgium.ORCID 0000-0001-8516-5856
Bart LoeysCentre of Medical Genetics, Antwerp University Hospital, University of Antwerp, 2650 Antwerp, Belgium.ORCID 0000-0003-3703-9518

Funding

European Research Council ERC-COG-2017-771945
6 · The paper itself

Abstract

Cardiovascular outcome in Marfan syndrome (MFS) patients most prominently depends on aortic aneurysm progression with subsequent aortic dissection. Angiotensin II receptor blockers (ARBs) prevent aneurysm formation in MFS mouse models. In patients, ARBs only slow down aortic dilation. Downstream signalling from the angiotensin II type 1 receptor (AT1R) is mediated by G proteins and β-arrestin recruitment. AT1R also interacts with the monocyte chemoattractant protein-1 (MCP-1) receptor, resulting in inflammation. In this study, we explore the targeting of β-arrestin signalling in MFS mice by administering TRV027. Furthermore, because high doses of the ARB losartan, which has been proven beneficial in MFS, cannot be achieved in humans, we investigate a potential additive effect by combining lower concentrations of losartan (25 mg/kg/day and 5 mg/kg/day) with barbadin, a β-arrestin blocker, and DMX20, a C-C chemokine receptor type 2 (CCR2) blocker. A high dose of losartan (50 mg/kg/day) slowed down aneurysm progression compared to untreated MFS mice (1.73 ± 0.12 vs. 1.96 ± 0.08 mm,

Indexed as

Angiotensin II Type 1 Receptor BlockersAortic AneurysmLosartanMarfan SyndromeSignal TransductionAngiotensin Receptor AntagonistsAnimalsAorta, ThoracicDisease Models, AnimalDrug CombinationsHumansMiceOligopeptidesPyrimidinesReceptor, Angiotensin, Type 1AGTR1 protein, humanAngiotensin II Type 1 Receptor BlockersAngiotensin Receptor AntagonistsbarbadinDrug CombinationsLosartanOligopeptidesPyrimidinesReceptor, Angiotensin, Type 1Sar-Arg-Val-Tyr-Ile-His-Pro-Ala-OHaortic aneurysmAT1R antagonismMarfan syndromeβ-arrestin

Identifiers

PMID38732244
PMCPMC11084825

What Socratic holds

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LicenceCC BY
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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 Socratic graph.