Mast cells drive pathologic vascular lesions in Takayasu arteritis.
Actins
/ metabolism
Adult
Animals
Aorta
Capillary Permeability
Cells, Cultured
Collagen Type I
/ metabolism
Female
Fibroblasts
/ metabolism
Fibronectins
/ metabolism
Fibrosis
Human Umbilical Vein Endothelial Cells
Humans
Interleukin-33
/ blood
Male
Mast Cells
/ metabolism
Mice, Inbred C57BL
Mice, Mutant Strains
Middle Aged
Neovascularization, Physiologic
Takayasu Arteritis
/ blood
Large vessel vasculitis
Takayasu
mast cell
vascular remodeling
Journal
The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
received:
04
12
2020
revised:
30
04
2021
accepted:
04
05
2021
pubmed:
17
5
2021
medline:
4
3
2022
entrez:
16
5
2021
Statut:
ppublish
Résumé
Takayasu arteritis (TAK) is a large vessel vasculitis resulting in artery wall remodeling with segmental stenosis and/or aneurysm formation. Mast cells (MCs) are instrumental in bridging cell injury and inflammatory response. This study sought to investigate the contribution of MCs on vessel permeability, angiogenesis, and fibrosis in patients with TAK. MC activation and their tissue expression were assessed in sera and in aorta from patients with TAK and from healthy donors (HDs). In vivo permeability was assessed using a modified Miles assay. Subconfluent cultured human umbilic vein endothelial cells and fibroblasts were used in vitro to investigate the effects of MC mediators on angiogenesis and fibrogenesis. This study found increased levels of MC activation markers (histamine and indoleamine 2,3-dioxygenase) in sera of patients with TAK compared with in sera of HDs. Marked expression of MCs was shown in aortic lesions of patients with TAK compared with in those of noninflammatory aorta controls. Using Miles assay, this study showed that sera of patients with TAK significantly increased vascular permeability in vivo as compared with that of HDs. Vessel permeability was abrogated in MC-deficient mice. MCs stimulated by sera of patients with TAK supported neoangiogenesis (increased human umbilic vein endothelial cell proliferation and branches) and fibrosis by inducing increased production of fibronectin, type 1 collagen, and α-smooth muscle actin by fibroblasts as compared to MCs stimulated by sera of HD. MCs are a key regulator of vascular lesions in patients with TAK and may represent a new therapeutic target in large vessel vasculitis.
Sections du résumé
BACKGROUND
Takayasu arteritis (TAK) is a large vessel vasculitis resulting in artery wall remodeling with segmental stenosis and/or aneurysm formation. Mast cells (MCs) are instrumental in bridging cell injury and inflammatory response.
OBJECTIVES
This study sought to investigate the contribution of MCs on vessel permeability, angiogenesis, and fibrosis in patients with TAK.
METHODS
MC activation and their tissue expression were assessed in sera and in aorta from patients with TAK and from healthy donors (HDs). In vivo permeability was assessed using a modified Miles assay. Subconfluent cultured human umbilic vein endothelial cells and fibroblasts were used in vitro to investigate the effects of MC mediators on angiogenesis and fibrogenesis.
RESULTS
This study found increased levels of MC activation markers (histamine and indoleamine 2,3-dioxygenase) in sera of patients with TAK compared with in sera of HDs. Marked expression of MCs was shown in aortic lesions of patients with TAK compared with in those of noninflammatory aorta controls. Using Miles assay, this study showed that sera of patients with TAK significantly increased vascular permeability in vivo as compared with that of HDs. Vessel permeability was abrogated in MC-deficient mice. MCs stimulated by sera of patients with TAK supported neoangiogenesis (increased human umbilic vein endothelial cell proliferation and branches) and fibrosis by inducing increased production of fibronectin, type 1 collagen, and α-smooth muscle actin by fibroblasts as compared to MCs stimulated by sera of HD.
CONCLUSIONS
MCs are a key regulator of vascular lesions in patients with TAK and may represent a new therapeutic target in large vessel vasculitis.
Identifiants
pubmed: 33992671
pii: S0091-6749(21)00734-X
doi: 10.1016/j.jaci.2021.05.003
pii:
doi:
Substances chimiques
ACTA2 protein, human
0
Actins
0
Collagen Type I
0
Fibronectins
0
Interleukin-33
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
292-301.e3Informations de copyright
Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.