GOMEZ, Ingrid, WARD, Ben, SOUILHOL, Celine, RECARTI, Chiara, ARIAANS, Mark, JOHNSTON, Jessica, BURNETT, Amanda, MAHMOUD, Marwa, LUONG, Le Anh, WEST, Laura, LONG, Merete, PARRY, Sion, WOODS, Rachel, HULSTON, Carl, BENEDIKTER, Birke, NIESPOLO, Chiara, BAZAZ, Rohit, FRANCIS, Sheila, KISS-TOTH, Endre, VAN ZANDVOORT, Marc, SCHOBER, Andreas, HELLEWELL, Paul, EVANS, Paul C and RIDGER, Victoria (2020). Neutrophil microvesicles drive atherosclerosis by delivering miR-155 to atheroprone endothelium. Nature Communications, 11 (1): 214. [Article]
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s41467-019-14043-y.pdf - Published Version
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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.
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