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, Chiara Niespolo, Rohit Bazaz, Sheila Francis, Endre Kiss-Toth, Marc van ZandvoortAndreas Schober, Paul Hellewell, Paul C. Evans, Victoria Ridger*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

59 Citations (Web of Science)

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.

Original languageEnglish
Article number214
Number of pages18
JournalNature Communications
Volume11
Issue number1
DOIs
Publication statusPublished - 10 Jan 2020

Keywords

  • CELL-DERIVED MICROPARTICLES
  • SMOOTH-MUSCLE-CELLS
  • FACTOR-KAPPA-B
  • ADHESION MOLECULE
  • EXPRESSION
  • PLATELET
  • PATHWAY
  • INFLAMMATION
  • ASSOCIATION
  • ACTIVATION

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