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

Gomez, Ingrid; Ward, Ben; Souilhol, Celine; Recarti, Chiara; Ariaans, Mark; Johnston, Jessica; Burnett, Amanda; Mahmoud, Marwa; Le, Anh Luong; West, Laura; Long, Merete; Parry, Sion; Woods, Rachel; Hulston, Carl; Benedikter, Birke; Niespolo, Chiara; Bazaz, Rohit; Francis, Sheila; Kiss-Toth, Endre; Zandvoort, Marc van; Schober, Andreas; Hellewell, Paul; Evans, Paul C. und Ridger, Victoria (2020): Neutrophil microvesicles drive atherosclerosis by delivering miR-155 to atheroprone endothelium. In: Nature Communications, Bd. 11, Nr. 1, 214

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-kappa B activation. Similarly, neutrophil microvesicles increase miR-155 and enhance NF-kappa B 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 2041-1723
• Sprache: Englisch