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

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, Rohit Bazaz, Sheila Francis, Endre Kiss-Toth, Marc van Zandvoort, Andreas Schober, Paul Hellewell, Paul C. Evans and Victoria Ridger

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Received: 27th April 18

Neutrophils have been implicated in the pathogenesis of atherosclerosis, a lipid-driven disease of arteries, but they are seldom found in atherosclerotic plaques. To resolve this longstanding paradox, we investigated whether neutrophil-derived microvesicles may influence arterial pathophysiology. Clinical and pre-clinical studies revealed that levels of circulating neutrophil microvesicles were enhanced by exposure to a high fat diet, a known risk factor for atherosclerosis. Neutrophil microvesicles accumulated at disease-prone regions of arteries that are exposed to complex flow patterns, and they promoted vascular inflammation and atherosclerosis in a murine model. Using cultured endothelial cells exposed to disturbed flow, it was demonstrated that neutrophil microvesicles promoted inflammatory gene expression by delivering a microRNA (miR-155) that enhanced NF-kB activation. Similary, neutrophil microvesicles increased miR-155 and enhanced NF-kB at disease-prone sites of disturbed flow in arteries of mice. We conclude that delivery of microvesicles carrying miR-155 to disease-prone regions of arteries provides a novel mechanism by which neutrophils contribute to vascular inflammation and atherogenesis.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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