TY - JOUR T1 - Neutrophil microvesicles drive atherosclerosis by delivering <em>miR-155</em> to atheroprone endothelium JF - bioRxiv DO - 10.1101/319392 SP - 319392 AU - Ingrid Gomez AU - Ben Ward AU - Celine Souilhol AU - Chiara Recarti AU - Mark Ariaans AU - Jessica Johnston AU - Amanda Burnett AU - Marwa Mahmoud AU - Le Anh Luong AU - Laura West AU - Merete Long AU - Sion Parry AU - Rachel Woods AU - Carl Hulston AU - Birke Benedikter AU - Rohit Bazaz AU - Sheila Francis AU - Endre Kiss-Toth AU - Marc van Zandvoort AU - Andreas Schober AU - Paul Hellewell AU - Paul C. Evans AU - Victoria Ridger Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/05/24/319392.abstract N2 - 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-κB activation. Similary, neutrophil microvesicles increased miR-155 and enhanced NF-κB 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.Non-standard Abbreviations and AcronymsApoE-/-apolipoprotein E deficientHCAEChuman coronary artery endothelial cells (HCAEC)ICAM-1intercellular adhesion molecule-1miRsmicro RNAMVsmicrovesiclesNETosisneutrophil exracellular trap formationNF-κBnuclear factorNMVsneutrophil-derived microvesiclesOSSoscillatory shear stressqPCRquantitative polymerase chain reactionRT-PCRreverse transcription polymerase chain reactionREEresting energy expenditureTNFtumor necrosis factorTRPStunable Resistive Pulse SensingVCAM-1vascular cell adhesion molecule-1 ER -