# 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
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# 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](https://eprints.gla.ac.uk/view/journal_volume/Circulation_Research.html)*, 126,
pp. 988-1003.
(doi: [10.1161/CIRCRESAHA.119.315428](https://doi.org/10.1161/CIRCRESAHA.119.315428))
(PMID:[32065054](https://europepmc.org/abstract/MED/32065054))
(PMCID:[PMC7147427](https://europepmc.org/articles/PMC7147427))
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| Preview | [Text](https://eprints.gla.ac.uk/210543/1/210543.pdf) 210543.pdf - Published Version Available under License [Creative Commons Attribution](http://creativecommons.org/licenses/by/4.0/). 10MB |
## 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.
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| Item Type: | Articles |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | [Graham, Dr Delyth](https://eprints.gla.ac.uk/view/author/3999.html) and [Nguyen Dinh Cat, Dr Aurelie](https://eprints.gla.ac.uk/view/author/29103.html) and [Siedlinski, Mr Mateusz](https://eprints.gla.ac.uk/view/author/51728.html) and [Salmeron-Sanchez, Professor Manuel](https://eprints.gla.ac.uk/view/author/30067.html) and [Guzik, Professor Tomasz](https://eprints.gla.ac.uk/view/author/30489.html) and [Mcginnigle, Dr Eilidh](https://eprints.gla.ac.uk/view/author/29319.html) and [Nosalski, Dr Ryszard](https://eprints.gla.ac.uk/view/author/33009.html) and [Maffia, Professor Pasquale](https://eprints.gla.ac.uk/view/author/11057.html) and [Skiba, Mr Dominik](https://eprints.gla.ac.uk/view/author/31075.html) and [Denby, Dr Laura](https://eprints.gla.ac.uk/view/author/8179.html) and [Cantini, Dr Marco](https://eprints.gla.ac.uk/view/author/30437.html) and [Medina-Ruiz, Dr Laura](https://eprints.gla.ac.uk/view/author/29817.html) and [Graham, Professor Gerard](https://eprints.gla.ac.uk/view/author/5334.html) |
| Authors: | [Nosalski, R.](https://eprints.gla.ac.uk/view/author/33009.html), [Siedlinski, M.](https://eprints.gla.ac.uk/view/author/51728.html), [Denby, L.](https://eprints.gla.ac.uk/view/author/8179.html), [Mcginnigle, E.](https://eprints.gla.ac.uk/view/author/29319.html), Nowak, M., [Nguyen Dinh Cat, A.](https://eprints.gla.ac.uk/view/author/29103.html), [Medina-Ruiz, L.](https://eprints.gla.ac.uk/view/author/29817.html), [Cantini, M.](https://eprints.gla.ac.uk/view/author/30437.html), [Skiba, D.](https://eprints.gla.ac.uk/view/author/31075.html), Wilk, G., Osmenda, G., Rodor, J., [Salmeron-Sanchez, M.](https://eprints.gla.ac.uk/view/author/30067.html), [Graham, G.](https://eprints.gla.ac.uk/view/author/5334.html), [Maffia, P.](https://eprints.gla.ac.uk/view/author/11057.html), [Graham, D.](https://eprints.gla.ac.uk/view/author/3999.html), Baker, A. H., and [Guzik, T. J.](https://eprints.gla.ac.uk/view/author/30489.html) |
| College/School: | [College of Medical Veterinary and Life Sciences](https://eprints.gla.ac.uk/view/divisions/20000000/) > [School of Cardiovascular & Metabolic Health](https://eprints.gla.ac.uk/view/divisions/25200000/) [College of Medical Veterinary and Life Sciences](https://eprints.gla.ac.uk/view/divisions/20000000/) > [School of Infection & Immunity](https://eprints.gla.ac.uk/view/divisions/25300000/) [College of Science and Engineering](https://eprints.gla.ac.uk/view/divisions/30000000/) > [School of Engineering](https://eprints.gla.ac.uk/view/divisions/30300000/) > [Biomedical Engineering](https://eprints.gla.ac.uk/view/divisions/30303000/) |
| Research Centre: | [College of Medical Veterinary and Life Sciences](https://eprints.gla.ac.uk/view/centres/MVLS10000/) > [School of Infection & Immunity](https://eprints.gla.ac.uk/view/centres/MVLS15300/) > [Centre for Immunobiology](https://eprints.gla.ac.uk/view/centres/MVLS15310/) |
| Journal Name: | [Circulation Research](https://eprints.gla.ac.uk/view/journal_volume/Circulation_Research.html) |
| 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 |
University Staff: [Request a correction](https://eprints.gla.ac.uk/cgi/request_correction?eprintid=210543) | Enlighten Editors: [Update this record](https://eprints.gla.ac.uk/cgi/users/home?screen=EPrint::View&eprintid=210543)
Funder and Project Information
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ENG - Biomedical Engineering
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| | |
| --- | --- |
| ID Code: | 210543 |
| Depositing User: | [Ms Jacqui Brannan](https://eprints.gla.ac.uk/profile/6299) |
| 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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