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http://bura.brunel.ac.uk/handle/2438/20049
Title: | Neutrophil microvesicles drive atherosclerosis by delivering miR-155 to atheroprone endothelium |
Authors: | Gomez, I Ward, B Souilhol, C Recarti, C Ariaans, M Johnston, J Burnett, A Mahmoud, M Luong, LA West, L Long, M Parry, S Woods, R Hulston, C Benedikter, B Niespolo, C Bazaz, R Francis, S Kiss-Toth, E van Zandvoort, M Schober, A Hellewell, P Evans, PC Ridger, V |
Issue Date: | 2020 |
Publisher: | Springer Science and Business Media LLC |
Citation: | Nature Communications, 2020, 11 (1) |
Abstract: | 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. |
URI: | http://bura.brunel.ac.uk/handle/2438/20049 |
DOI: | http://dx.doi.org/10.1038/s41467-019-14043-y |
ISSN: | 214 214 http://dx.doi.org/10.1038/s41467-019-14043-y 2041-1723 |
Other Identifiers: | 214 214 |
Appears in Collections: | Dept of Life Sciences Research Papers |
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