Endothelium-derived extracellular vesicles promote splenic monocyte mobilization in myocardial infarction

被引：86

作者：

Akbar, Naveed ^{[1
]}

Digby, Janet E. ^{[1
]}

Cahill, Thomas J. ^{[1
]}

Tavare, Abhijeet N. ^{[1
]}

Corbin, Alastair L. ^{[2
]}

Saluja, Sushant ^{[1
]}

Dawkins, Sam ^{[1
]}

Edgar, Laurienne ^{[1
]}

Rawlings, Nadiia ^{[1
]}

Ziberna, Klemen ^{[1
]}

McNeill, Eileen ^{[1
]}

Johnson, Errin ^{[4
]}

Aljabali, Alaa A. ^{[1
]}

Dragovic, Rebecca A. ^{[5
]}

Rohling, Mala ^{[6
]}

Belgard, T. Grant ^{[7
]}

Udalova, Irina A. ^{[2
]}

Greaves, David R. ^{[4
]}

Channon, Keith M. ^{[1
]}

Riley, Paul R. ^{[6
]}

Anthony, Daniel C. ^{[8
]}

Choudhury, Robin P. ^{[1
,9
]}

机构：

[1] Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford, England

[2] Univ Oxford, Kennedy Inst Rheumatol, Oxford, England

[3] Univ Oxford, OxAMI Study Detailed Supplemental Acknowledgments, Oxford, England

[4] Univ Oxford, Sir William Dunn Sch Pathol, Oxford, England

[5] Univ Oxford, Nuffield Dept Obstet & Gynaecol, Oxford, England

[6] Univ Oxford, Dept Physiol Anat & Genet, Oxford, England

[7] Verge Genom, San Francisco, CA USA

[8] Univ Oxford, Radcliffe Dept Med, Expt Neuropathol, Dept Pharmacol, Oxford, England

[9] Univ Oxford, Radcliffe Dept Med, Acute Vasc Imaging Ctr, Oxford, England

来源：

JCI INSIGHT | 2017年 / 2卷 / 17期

关键词：

MEDIATED TRANSFER; DOWN-REGULATION; EXOSOMES; MICRORNAS; ADHESION; GENE; ATHEROSCLEROSIS; MICROPARTICLES; PROLIFERATION; INFLAMMATION;

D O I：

10.1172/jci.insight.93344

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

100103 [病原生物学]; 100218 [急诊医学];

摘要：

Transcriptionally activated monocytes are recruited to the heart after acute myocardial infarction (AMI). After AMI in mice and humans, the number of extracellular vesicles (EVs) increased acutely. In humans, EV number correlated closely with the extent of myocardial injury. We hypothesized that EVs mediate splenic monocyte mobilization and program transcription following AMI. Some plasma EVs bear endothelial cell (EC) integrins, and both proinflammatory stimulation of ECs and AMI significantly increased VCAM-1-positive EV release. Injected EC-EVs localized to the spleen and interacted with, and mobilized, splenic monocytes in otherwise naive, healthy animals. Analysis of human plasma EV-associated miRNA showed 12 markedly enriched miRNAs after AMI; functional enrichment analyses identified 1,869 putative mRNA targets, which regulate relevant cellular functions (e.g., proliferation and cell movement). Furthermore, gene ontology termed positive chemotaxis as the most enriched pathway for the miRNA-mRNA targets. Among the identified EV miRNAs, EC-associated miRNA-126-3p and -5p were highly regulated after AMI. miRNA-126-3p and -5p regulate cell adhesion- and chemotaxis-associated genes, including the negative regulator of cell motility, plexin-B2. EC-EV exposure significantly downregulated plexin-B2 mRNA in monocytes and upregulated motility integrin ITGB2. These findings identify EVs as a possible novel signaling pathway by linking ischemic myocardium with monocyte mobilization and transcriptional activation following AMI.

引用

页数：17

共 69 条

[1]

MicroRNA-126 in Atherosclerosis [J].