Gomez et al., 2020 - Nature Communications.pdf (7.33 MB)

Neutrophil microvesicles drive atherosclerosis by delivering miR-155 to atheroprone endothelium

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posted on 24.01.2020, 16:11 by Ingrid Gomez, Ben Ward, Celine Souilhol, Chiara Recarti, Mark Ariaans, Jessica Johnston, Amanda Burnett, Marwa Mahmoud, Le Anh Luong, Laura West, Merete Long, Sion Parry, Rachel Woods, Carl Hulston, Birke Benedikter, Chiara Niespolo, Rohit Bazaz, Sheila Francis, Endre Kiss-Toth, Marc van Zandvoort, Andreas Schober, Paul Hellewell, Paul C Evans, Victoria Ridger
Neutrophils are implicated in the pathogenesis of atherosclerosis but are seldom detected in atherosclerotic plaques. We investigated whether neutrophil-derived microvesicles may influence arterial pathophysiology. Here we report that levels of circulating neutrophil microvesicles are enhanced by exposure to a high fat diet, a known risk factor for atherosclerosis. Neutrophil microvesicles accumulate at disease-prone regions of arteries exposed to disturbed flow patterns, and promote vascular inflammation and atherosclerosis in a murine model. Using cultured endothelial cells exposed to disturbed flow, we demonstrate that neutrophil microvesicles promote inflammatory gene expression by delivering miR-155, enhancing NF-κB activation. Similarly, neutrophil microvesicles increase miR-155 and enhance NF-κB at disease-prone sites of disturbed flow in vivo. Enhancement of atherosclerotic plaque formation and increase in macrophage content by neutrophil microvesicles is dependent on miR-155. We conclude that neutrophils contribute to vascular inflammation and atherogenesis through delivery of microvesicles carrying miR-155 to disease-prone regions.

Funding

British Heart Foundation Programme Grant (CS, PE)

British Heart Foundation Project Grants PG/09/067/27901 (AB, VR), PG/13/55/30365 (LW, SF), PG/14/38/30862 (CR, VR), PG/16/44/32146 (JJ, EKT, SF)

British Heart Foundation Studentship FS/14/8/30605 (BW, VR)

MRC Fellowship MR/K023977/1 (RB)

European Union’s Horizon 2020 Marie Skłodowska-Curie Innovative Training Network, TRAIN 721532 (CN)

History

School

  • Sport, Exercise and Health Sciences

Published in

Nature Communications

Volume

11

Publisher

Springer Nature

Version

VoR (Version of Record)

Rights holder

© The Authors

Publisher statement

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Acceptance date

11/12/2019

Publication date

2020-01-10

Copyright date

2020

ISSN

2041-1723

eISSN

2041-1723

Language

en

Depositor

Dr Carl Hulston. Deposit date: 23 January 2020

Article number

214

Licence

Exports

Loughborough Publications

Categories

Licence

Exports