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bioRxiv · 10.1101/2025.02.19.638859

Neutrophil derived microvesicles induce endothelial cell dysfunction associated with atherosclerotic plaque erosion.

Dow, R.·Card, E.·Gurung, S.·Evans, P. C.·Ridger, V.
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Abstract

Atherosclerosis is a major cause of death globally. It is characterised by the development of fibro-fatty lesions in the artery wall that can impede blood flow and lead to myocardial infarction. Historically, research has focused primarily on plaque rupture. However, the importance of erosion of the endothelium leading to thrombosis in plaques with lower lipid content, fewer inflammatory cells and a thick fibrous cap has emerged. Neutrophils have recently been implicated in plaque erosion through the induction of endothelial cell dysfunction. Neutrophils produce 0.1-1m extracellular vesicles (microvesicles) from their cell membrane that are linked with atherosclerotic plaque progression. The hypothesis that neutrophil microvesicles affect plaque erosion through driving endothelial cell dysfunction and platelet adhesion was investigated. Peripheral blood neutrophils and platelets were isolated from healthy subjects and neutrophils stimulated with native LDL to induce microvesicle release. These microvesicles were found to contain proteases capable of degrading extracellular matrix proteins. Incubation of human coronary artery endothelial cells with neutrophil microvesicles lead to an increase in apoptosis and detachment, and a decrease in migration and proliferation in the endothelial cells. Moreover, microvesicles induced an increase in both platelet P-selectin expression and platelet-endothelial cell interaction. This study demonstrates the propensity of neutrophil microvesicles to promote functions within human coronary artery endothelial cells that may predispose the endothelium to erosion and thrombosis and identifies a potential link between a known risk factor for atherosclerosis, elevated LDL cholesterol, and the production of neutrophil microvesicles. These findings highlight the need for further research to better understand the effects of neutrophil microvesicles in atherosclerosis.

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Dow, R., Card, E., Gurung, S., Evans, P. C., Ridger, V.. 2025-02-21. Neutrophil derived microvesicles induce endothelial cell dysfunction associated with atherosclerotic plaque erosion.. https://doi.org/10.1101/2025.02.19.638859

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