Neutrophil microvesicles drive atherosclerosis by delivering miR-155 to atheroprone endothelium
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 ex...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Springer Nature
2020
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| _version_ | 1797098200082939904 |
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| author | Gomez, I Ward, B Souilhol, C Recarti, C Ariaans, M Johnston, J Burnett, A Mahmoud, M Luong, L 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, P Ridger, V |
| author_facet | Gomez, I Ward, B Souilhol, C Recarti, C Ariaans, M Johnston, J Burnett, A Mahmoud, M Luong, L 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, P Ridger, V |
| author_sort | Gomez, I |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T05:06:13Z |
| format | Journal article |
| id | oxford-uuid:da01a50e-70ad-4fac-a574-4327a2702f8b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:06:13Z |
| publishDate | 2020 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:da01a50e-70ad-4fac-a574-4327a2702f8b2022-03-27T09:00:07ZNeutrophil microvesicles drive atherosclerosis by delivering miR-155 to atheroprone endotheliumJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:da01a50e-70ad-4fac-a574-4327a2702f8bEnglishSymplectic Elements at OxfordSpringer Nature2020Gomez, IWard, BSouilhol, CRecarti, CAriaans, MJohnston, JBurnett, AMahmoud, MLuong, LWest, LLong, MParry, SWoods, RHulston, CBenedikter, BNiespolo, CBazaz, RFrancis, SKiss-Toth, EVan Zandvoort, MSchober, AHellewell, PEvans, PRidger, VNeutrophils 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. |
| spellingShingle | Gomez, I Ward, B Souilhol, C Recarti, C Ariaans, M Johnston, J Burnett, A Mahmoud, M Luong, L 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, P Ridger, V Neutrophil microvesicles drive atherosclerosis by delivering miR-155 to atheroprone endothelium |
| title | Neutrophil microvesicles drive atherosclerosis by delivering miR-155 to atheroprone endothelium |
| title_full | Neutrophil microvesicles drive atherosclerosis by delivering miR-155 to atheroprone endothelium |
| title_fullStr | Neutrophil microvesicles drive atherosclerosis by delivering miR-155 to atheroprone endothelium |
| title_full_unstemmed | Neutrophil microvesicles drive atherosclerosis by delivering miR-155 to atheroprone endothelium |
| title_short | Neutrophil microvesicles drive atherosclerosis by delivering miR-155 to atheroprone endothelium |
| title_sort | neutrophil microvesicles drive atherosclerosis by delivering mir 155 to atheroprone endothelium |
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