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

Nat Commun. 2020 Jan 10;11(1):214. doi: 10.1038/s41467-019-14043-y.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atherosclerosis / metabolism*
  • Atherosclerosis / pathology
  • Diet, High-Fat
  • Disease Models, Animal
  • Endothelial Cells
  • Endothelium / metabolism*
  • Endothelium / pathology
  • Gene Expression Regulation
  • Humans
  • Macrophages / metabolism
  • Mice
  • Mice, Knockout, ApoE
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • NF-kappa B / metabolism
  • Neutrophils / metabolism*
  • Plaque, Atherosclerotic / metabolism
  • Plaque, Atherosclerotic / pathology

Substances

  • MicroRNAs
  • Mirn155 microRNA, mouse
  • NF-kappa B