Evidence map›Paper›PMID 38636100›Full record

ArticleCardiovascular research2024

The proprotein convertase FURIN is a novel aneurysm predisposition gene impairing TGF-β signalling.

Zongsheng He, Arne S IJpma, Dianne Vreeken, Daphne Heijsman, Karen Rosier, Hence J M Verhagen, Jorg L de Bruin, Hennie T Brüggenwirth, Jolien W Roos-Hesselink, Jos A Bekkers and 4 more

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Article in Cardiovascular research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
3.4field-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

4 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Transforming growth factor-beta (TGF-β) in the pathogenesis of hereditary thoracic aneurysm disorders.Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 2 institutions in 2 countries.

Zongsheng HeLaboratory of Biochemical Neuroendocrinology, Department of Human Genetics, KU Leuven, Gasthuisberg O/N 06, Herestraat 49, Box 607, Leuven B-3000, Belgium.
Arne S IJpmaDepartment of Pathology, Erasmus MC University Medical Center, Dr. Molewater 40, PO BOX 2040, Rotterdam 3000 CA, The Netherlands.
Dianne VreekenDepartment of Cardiology, Erasmus MC University Medical Center, Dr. Molewaterplein 40, PO BOX 2040, Rotterdam 3015 GD, The Netherlands.
Daphne HeijsmanDepartment of Clinical Genetics, Erasmus MC University Medical Center, Dr Molewaterplein 40 PO BOX 2040, 3000CA Rotterdam, The Netherlands.
Karen RosierLaboratory of Biochemical Neuroendocrinology, Department of Human Genetics, KU Leuven, Gasthuisberg O/N 06, Herestraat 49, Box 607, Leuven B-3000, Belgium.
Hence J M VerhagenDepartment of Surgery, Erasmus MC University Medical Center, Dr. Molewaterplein 40, PO BOX 2040, 3000 CA Rotterdam, The Netherlands.
Jorg L de BruinDepartment of Surgery, Erasmus MC University Medical Center, Dr. Molewaterplein 40, PO BOX 2040, 3000 CA Rotterdam, The Netherlands.
Hennie T BrüggenwirthDepartment of Clinical Genetics, Erasmus MC University Medical Center, Dr Molewaterplein 40 PO BOX 2040, 3000CA Rotterdam, The Netherlands.
Jolien W Roos-HesselinkDepartment of Cardiology, Erasmus MC University Medical Center, Dr. Molewaterplein 40, PO BOX 2040, Rotterdam 3015 GD, The Netherlands.
Jos A BekkersDepartment of Cardiothoracic Surgery, Erasmus MC University Medical Center, Dr. Molewaterplein 40, PO BOX 2040, 3000 CA Rotterdam, The Netherlands.
Danny F E HuylebroeckDepartment of Cell Biology, Erasmus MC University Medical Center, Dr. Molewaterplein 40, PO BOX 2040, 3000 CA Rotterdam, The Netherlands.
Heleen M M van BeusekomDepartment of Cardiology, Erasmus MC University Medical Center, Dr. Molewaterplein 40, PO BOX 2040, Rotterdam 3015 GD, The Netherlands.
John W M CreemersLaboratory of Biochemical Neuroendocrinology, Department of Human Genetics, KU Leuven, Gasthuisberg O/N 06, Herestraat 49, Box 607, Leuven B-3000, Belgium.ORCID 0000-0003-2518-9295
Danielle Majoor-KrakauerDepartment of Clinical Genetics, Erasmus MC University Medical Center, Dr Molewaterplein 40 PO BOX 2040, 3000CA Rotterdam, The Netherlands.ORCID 0000-0003-3440-8541
Erasmus MC · NLKU Leuven · BE

Funding

ASIJDMKHVBNational Natural Science Foundation of China 82203318Natural Science Foundation of Chongqing CSTB2022NSCQ-MSX0880
6 · The paper itself

Abstract

aimsAortic aneurysms (AA) frequently involve dysregulation of transforming growth factor β (TGF-β)-signalling in the aorta. Here, FURIN was tested as aneurysm predisposition gene given its role as proprotein convertase in pro-TGF-β maturation. METHODS AND

resultsRare FURIN variants were detected by whole-exome sequencing of 781 unrelated aortic aneurysm patients and affected relatives. Thirteen rare heterozygous FURIN variants occurred in 3.7% (29) unrelated index AA patients, of which 72% had multiple aneurysms or a dissection. FURIN maturation and activity of these variants were decreased in vitro. Patient-derived fibroblasts showed decreased pro-TGF-β processing, phosphorylation of downstream effector SMAD2 and kinases ERK1/2, and steady-state mRNA levels of the TGF-β-responsive ACTA2 gene. In aortic tissue, collagen and fibrillin fibres were affected. One variant (R745Q), observed in 10 unrelated cases, affected TGF-β signalling variably, indicating effect modification by individual genetic backgrounds.

conclusionFURIN is a novel, frequent genetic predisposition for abdominal-, thoracic-, and multiple aortic or middle sized artery aneurysms in older patients, by affecting intracellular TGF-β signalling, depending on individual genetic backgrounds.

Indexed as

FurinGenetic Predisposition to DiseaseSignal TransductionSmad2 ProteinTransforming Growth Factor betaActinsAgedAortic AneurysmAortic Aneurysm, AbdominalAortic Aneurysm, ThoracicAortic DissectionCells, CulturedExome SequencingFemaleFibroblastsHeterozygoteACTA2 protein, humanActinsFurinFURIN protein, humanSmad2 ProteinSMAD2 protein, humanTransforming Growth Factor betaAortic aneurysm geneFURINgenetic predispositionProprotein convertasePolygenicTGF-β

Identifiers

PMID38636100
PMCPMC11687399
OpenAlexW4394907647

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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.