Evidence map›Paper›PMID 40084998›Full record

ArticleRheumatology (Oxford, England)2025

Distinct landscapes of fibroblast subtypes in arteries of patients with giant cell arteritis.

Shuang Xu, William F Jiemy, Yannick van Sleen, Johanna Westra, Jacoba C Graver, Kornelis S M van der Geest, Peter Heeringa, Annemieke M H Boots, Elisabeth Brouwer, Maria Sandovici

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In one paragraph

Article in Rheumatology (Oxford, England), 2025. 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

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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

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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
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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

10 authors.

Shuang XuDepartment of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.ORCID 0000-0001-8071-2830
William F JiemyDepartment of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Yannick van SleenDepartment of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.ORCID 0000-0002-7382-8322
Johanna WestraDepartment of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.ORCID 0000-0002-6581-6508
Jacoba C GraverDepartment of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Kornelis S M van der GeestDepartment of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.ORCID 0000-0003-2798-6765
Peter HeeringaDepartment of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.ORCID 0000-0001-8684-763X
Annemieke M H BootsDepartment of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Elisabeth BrouwerDepartment of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.ORCID 0000-0002-5652-4423
Maria SandoviciDepartment of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.ORCID 0000-0002-4809-0653

Funding

AbbVieChina Scholarship Council #202006230100Dutch Arthritis SocietyInnovative Medicines Initiative 2 Joint Undertaking Immune-Image 831514Siemens Healthineers
6 · The paper itself

Abstract

objectiveGiant cell arteritis (GCA) is a systemic vasculitis of large- and medium-sized arteries characterized by granulomatous inflammation and vascular remodelling. Although fibroblasts are the predominant cell type in the adventitia, their role in GCA pathogenesis is largely unknown. This study aimed to investigate the distribution of fibroblast subtypes in relation to vascular remodelling in GCA.

methodsTemporal artery biopsies (TAB) from patients with GCA (n = 9) and controls (n = 15) and aorta tissues from GCA (n = 9)- and atherosclerosis (n = 11)-related aneurysms were examined. Immunohistochemical and immunofluorescence staining for fibroblast subtype markers (CD90, platelet-derived growth factor receptor α [PDGFRA], fibroblast activation protein [FAP], podoplanin [PDPN], CD248, α-smooth muscle actin [α-SMA]), cellular proliferation (Ki67) and remodelling-related growth factors (TGF-β, fibroblast growth factor 21 [FGF21], platelet-derived growth factor B [PDGFB]) were performed to evaluate the distribution of fibroblast subtypes in relation to active remodelling pathways. To evaluate the role of FAP in TGF-β-induced fibroblast proliferation, human aortic adventitial fibroblasts (HAoAF) were stimulated in vitro with TGF-β and transfected with small interfering RNA targeting FAP.

resultsIn GCA-TAB, CD90+FAP+ activated fibroblasts and CD90+PDPN+ immunofibroblasts were predominantly located in the adventitia. CD90+α-SMA+ myofibroblasts were observed mainly in the intima, and CD90+CD248+ fibroblasts in the adventitia-media border and intima. High FGF21 and PDGFB expression in the intima was associated with intimal hyperplasia in GCA-positive TAB. GCA-affected aortas showed a different landscape of fibroblast subtypes: CD90+FAP+ activated fibroblasts, CD90+PDPN+ immunofibroblasts and CD90+CD248+ fibroblasts accumulated especially in structurally disrupted media. Approximately 80% of proliferative fibroblasts in TAB and aorta were FAP positive. FAP knockdown suppressed TGFβ-induced proliferation of HAoAF in vitro.

conclusionThis study documents a distinct spatial distribution pattern of fibroblast subtypes in GCA-affected arteries. The data suggest different roles for fibroblasts in remodelling of specific arterial vascular beds in GCA.

Indexed as

FibroblastsGiant Cell ArteritisTemporal ArteriesAdventitiaAgedAged, 80 and overAortaAtherosclerosisCell ProliferationEndopeptidasesFemaleFibroblast Activation Protein AlphaHumansMaleMembrane ProteinsMiddle AgedEndopeptidasesFibroblast Activation Protein AlphaMembrane ProteinsTransforming Growth Factor betafibroblast subtypesgiant cell arteritisvascular remodelling

Identifiers

PMID40084998
PMCPMC12212911

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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.