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 language | English |
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Article number | 214 |
Number of pages | 18 |
Journal | Nature Communications |
Volume | 11 |
Issue number | 1 |
DOIs | |
Publication status | Published - 10 Jan 2020 |
Keywords
- CELL-DERIVED MICROPARTICLES
- SMOOTH-MUSCLE-CELLS
- FACTOR-KAPPA-B
- ADHESION MOLECULE
- EXPRESSION
- PLATELET
- PATHWAY
- INFLAMMATION
- ASSOCIATION
- ACTIVATION