Metadata

Title: T cell-derived miRNA-214 mediates perivascular fibrosis in hypertension
Category: general
UUID: 49db507e5263419a8f2963198b37aca0

Source URL: https://eprints.gla.ac.uk/210543/
Parent URL: https://eprints.gla.ac.uk/view/project_code/303613.html
Crawl Time: 2026-03-11T05:49:52+00:00

T cell-derived miRNA-214 mediates perivascular fibrosis in hypertension

Source: https://eprints.gla.ac.uk/210543/ Parent: https://eprints.gla.ac.uk/view/project_code/303613.html

T cell-derived miRNA-214 mediates perivascular fibrosis in hypertension

Nosalski, R. et al. (2020) T cell-derived miRNA-214 mediates perivascular fibrosis in hypertension. Circulation Research, 126, pp. 988-1003. (doi: 10.1161/CIRCRESAHA.119.315428) (PMID:32065054) (PMCID:PMC7147427)


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Abstract

Rationale: Despite increasing understanding of the prognostic importance of vascular stiffening linked to perivascular fibrosis in hypertension, the molecular and cellular regulation of this process is poorly understood. Objective: To study the functional role of microRNA-214 (miR-214) in the induction of perivascular fibrosis and endothelial dysfunction driving vascular stiffening. Methods and Results: Out of 381 miRs screened in the perivascular tissues (PVAT) in response to angiotensin II (Ang II)-mediated hypertension, miR-214 showed the highest induction (8-fold, p=0.0001). MiR-214 induction was pronounced in perivascular and circulating T cells, but not in PVAT adipocytes. Global deletion of miR-214-/- prevented Ang II-induced periaortic fibrosis Col1a1, Col3a1, Col5a1 and Tgfb1 expression, hydroxyproline accumulation and vascular stiffening, without difference in blood pressure. Mechanistic studies revealed that miR-214-/- mice were protected against endothelial dysfunction, oxidative stress and increased Nox2, all of which were induced by Ang II in WT mice. Ang II-induced recruitment of T cells into PVAT was abolished in miR-214-/- mice. Adoptive transfer of miR-214-/- T cells into RAG1-/- mice resulted in reduced perivascular fibrosis compared to the effect of WT T cells. Ang II induced hypertension caused significant change in the expression of 1380 T cell genes in WT, but only 51 in miR-214-/-. T cell activation, proliferation and chemotaxis pathways were differentially affected. miR-214-/- prevented Ang II-induction of pro-fibrotic T cell cytokines (IL-17, TNF-alpha, IL-9 and IFN-ý)and chemokine receptors (CCR1, CCR2, CCR4, CCR5, CCR6 and CXCR3). This manifested in reduced in vitro and in vivo T cell chemotaxis resulting in attenuation of profibrotic perivascular inflammation. Translationally, we show that miR-214 is increased in plasma of hypertensive patients and is directly correlated to pulse wave velocity as a measure of vascular stiffness. Conclusions: T cell-derived miR-214 controls pathological perivascular fibrosis in hypertension mediated by T cell recruitment and local profibrotic cytokine release.


Item Type:	Articles
Status:	Published
Refereed:	Yes
Glasgow Author(s) Enlighten ID:	Graham, Dr Delyth and Nguyen Dinh Cat, Dr Aurelie and Siedlinski, Mr Mateusz and Salmeron-Sanchez, Professor Manuel and Guzik, Professor Tomasz and Mcginnigle, Dr Eilidh and Nosalski, Dr Ryszard and Maffia, Professor Pasquale and Skiba, Mr Dominik and Denby, Dr Laura and Cantini, Dr Marco and Medina-Ruiz, Dr Laura and Graham, Professor Gerard
Authors:	Nosalski, R., Siedlinski, M., Denby, L., Mcginnigle, E., Nowak, M., Nguyen Dinh Cat, A., Medina-Ruiz, L., Cantini, M., Skiba, D., Wilk, G., Osmenda, G., Rodor, J., Salmeron-Sanchez, M., Graham, G., Maffia, P., Graham, D., Baker, A. H., and Guzik, T. J.
College/School:	College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Science and Engineering > School of Engineering > Biomedical Engineering
Research Centre:	College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
Journal Name:	Circulation Research
Publisher:	American Heart Association
ISSN:	0009-7330
ISSN (Online):	1524-4571
Published Online:	17 February 2020
Copyright Holders:	Copyright © 2020 The Authors
First Published:	First published in Circulation Research 126:988–1003
Publisher Policy:	Reproduced under a Creative Commons License

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Funder and Project Information

Project Code

Award No

Project Name

Principal Investigator

Funder's Name

Funder Ref

Lead Dept

170444

Assessing the contribution of microRNA to in-stent restenosis

Tomasz Guzik

British Heart Foundation (BHF)

FS/14/49/30838

Institute of Cardiovascular & Medical Sciences

300798

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Tomasz Guzik

European Research Council (ERC)

726318

CAMS - Cardiovascular Science

169623

Role of non-coding RNA in vascular pathology

Andrew Baker

British Heart Foundation (BHF)

RG/14/3/30706

Institute of Cardiovascular & Medical Sciences

190391

BHF Chair of Translational Cardiovascular Sciences

Andrew Baker

British Heart Foundation (BHF)

CH/11/2/28733

Institute of Cardiovascular & Medical Sciences

303613

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Marco Cantini

Medical Research Council (MRC)

MR/S005412/1

ENG - Biomedical Engineering

301095

UKRMP2 Acellular/Smart Materials 3D Architecture Hub

Manuel Salmeron-Sanchez

Medical Research Council (MRC)

MMRE_P75176 (MR/R015651/1

ENG - Biomedical Engineering

Deposit and Record Details


ID Code:	210543
Depositing User:	Ms Jacqui Brannan
Datestamp:	20 Feb 2020 11:43
Last Modified:	29 Oct 2024 15:01
Date of acceptance:	14 February 2020
Date of first online publication:	17 February 2020
Date Deposited:	20 February 2020

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