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

被引：124

作者：

Gomez, Ingrid ^{[1
]}

Ward, Ben ^{[1
,2
]}

Souilhol, Celine ^{[1
,2
]}

Recarti, Chiara ^{[1
,3
]}

Ariaans, Mark ^{[1
]}

Johnston, Jessica ^{[1
]}

Burnett, Amanda ^{[1
]}

Mahmoud, Marwa ^{[1
,4
]}

Le Anh Luong ^{[5
]}

West, Laura ^{[1
]}

Long, Merete ^{[1
]}

Parry, Sion ^{[6
]}

Woods, Rachel ^{[6
]}

Hulston, Carl ^{[6
]}

Benedikter, Birke ^{[7
]}

Niespolo, Chiara ^{[1
]}

Bazaz, Rohit ^{[1
]}

Francis, Sheila ^{[1
]}

Kiss-Toth, Endre ^{[1
]}

van Zandvoort, Marc ^{[3
]}

Schober, Andreas ^{[8
]}

Hellewell, Paul ^{[1
,9
]}

Evans, Paul C. ^{[1
,2
,10
]}

Ridger, Victoria ^{[1
,2
]}

机构：

[1] Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Sheffield, S Yorkshire, England

[2] Univ Sheffield, INSIGNEO Inst Silico Med, Sheffield, S Yorkshire, England

[3] Maastricht Univ, CARIM Sch Cardiovasc Dis, Dept Mol Cell Biol, Maastricht, Netherlands

[4] Emory Univ, Dept Med, Cardiovasc Mechanobiol & Nanomed, Atlanta, GA 30322 USA

[5] Queen Mary Univ, William Harvey Res Inst, London, England

[6] Loughborough Univ, Sch Sport Exercise & Hlth Sci, Loughborough, Leics, England

[7] Maastricht Univ, NUTRIM Sch Nutr & Translat Res Metab, Dept Med Microbiol, Maastricht, Netherlands

[8] Ludwig Maximilian Univ Munich, Expt Vasc Med, Munich, Germany

[9] Brunel Univ, Coll Hlth & Life Sci, London, England

[10] Univ Sheffield, Bateson Inst, Sheffield, S Yorkshire, England

来源：

NATURE COMMUNICATIONS | 2020年 / 11卷 / 01期

基金：

英国医学研究理事会;

关键词：

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

D O I：

10.1038/s41467-019-14043-y

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：18

共 63 条

[1]

Berckmans RJ, 2001, THROMB HAEMOSTASIS, V85, P639

[2]

Bloom RJ, 2014, NAT METHODS, V11, P1147, DOI [10.1038/NMETH.3100, 10.1038/nmeth.3100]

[3] Activated transcription factor nuclear factor-kappa B is present in the atherosclerotic lesion [J].