Delivery of MicroRNA-126 by Apoptotic Bodies Induces CXCL12-Dependent Vascular Protection

Zernecke, Alma; Bidzhekov, Kiril; Noels, Heidi; Shagdarsuren, Erdenechimeg; Gan, Lin; Denecke, Bernd; Hristov, Mihail; Köppel, Thomas; Jahantigh, Maliheh Nazari; Lutgens, Esther; Wang, Shusheng; Olson, Eric N.; Schober, Andreas; Weber, Christian

doi:10.1126/scisignal.2000610

Cited by 1,195 publications

(1,131 citation statements)

References 41 publications

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“…32,33 Electron microscopy of the cell-free fraction from G-CSF-mobilized bone marrows revealed large numbers of vesicles resembling exosomes ( Figure 4A) and others (not shown) morphologically similar to neutrophilderived apoptotic bodies described in the bone marrow. 34 Similar, but fewer, particles were visualized in the cell-free fraction of non-mobilized bone marrows (not shown).…”

Section: Microvesicle Production and Transfer To Hematopoietic Stem/pmentioning

confidence: 83%

MicroRNA126 contributes to granulocyte colony-stimulating factor-induced hematopoietic progenitor cell mobilization by reducing the expression of vascular cell adhesion molecule 1

Salvucci

Jiang²,

Gasperini³

et al. 2012

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundMobilization of hematopoietic stem/progenitor cells from the bone marrow to the peripheral blood by granulocyte colony-stimulating factor is the primary means to acquire stem cell grafts for hematopoietic cell transplantation. Since hematopoietic stem/progenitor cells represent a minority of all blood cells mobilized by granulocyte colony-stimulating factor, the underlying mechanisms need to be understood in order to develop selective drugs. Design and MethodsWe analyzed phenotypic, biochemical and genetic changes in bone marrow cell populations from granulocyte colony-stimulating factor-mobilized and control mice, and linked such changes to effective mobilization of hematopoietic stem/progenitor cells. ResultsWe show that granulocyte colony-stimulating factor indirectly reduces expression of surface vascular cell adhesion molecule 1 on bone marrow hematopoietic stem/progenitor cells, stromal cells and endothelial cells by promoting the accumulation of microRNA-126 (miR126)-containing microvescicles in the bone marrow extracellular compartment. We found that hematopoietic stem/progenitor cells, stromal cells and endothelial cells readily incorporate these miR126-loaded microvescicles, and that miR126 represses vascular cell adhesion molecule 1 expression on bone marrow hematopoietic stem/progenitor cells, stromal cells and endothelial cells. In line with this, miR126-null mice displayed a reduced mobilization response to granulocyte colony-stimulating factor. ConclusionsOur results implicate miR126 in the regulation of hematopoietic stem/progenitor cell trafficking between the bone marrow and peripheral sites, clarify the role of vascular cell adhesion molecule 1 in granulocyte colony-stimulating factor-mediated mobilization, and have important implications for improved approaches to selective mobilization of hematopoietic stem/progenitor cells.

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Section: Microvesicle Production and Transfer To Hematopoietic Stem/pmentioning

confidence: 83%

MicroRNA126 contributes to granulocyte colony-stimulating factor-induced hematopoietic progenitor cell mobilization by reducing the expression of vascular cell adhesion molecule 1

Salvucci

Jiang²,

Gasperini³

et al. 2012

Haematologica

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“…28,29 Previous studies have suggested that circulating miRNAs may act as extracellular communicators because they could be transferred to VECs and regulate atherosclerotic processes. [30][31][32] Extracellular miRNAs are especially adept at mediating gene regulation among cells in a microenvironment. 33 In this regard, subintimal inflammation and atherosclerotic lesions, which harbor complex multicellular microenvironments, may be a nexus of miRNA-based signaling.…”

Section: Discussionmentioning

confidence: 99%

Circulating MicroRNAs and the Occurrence of Acute Myocardial Infarction in Chinese Populations

Huang

Lü

et al. 2014

Circ Cardiovasc Genet

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A cute myocardial infarction (AMI) is a leading cause of morbidity and mortality worldwide. 1 Multiple conventional risk factors and serum atherosclerotic biomarkers have been established for coronary heart disease (CHD). 2 However, advances in genomics and proteomics, especially gene-expression profiling using microarray and quantitative real-time polymerase chain reaction (qPCR), have promoted the generation of many novel molecular biomarkers for AMI with potential clinical values. 3,4 Recently, microRNAs (miRNAs) have attracted extensive interest in the field of cardiovascular diseases. 5 Clinical Perspective on p 198MiRNAs are short, endogenous, noncoding RNAs that regulate gene expressions at the posttranscriptional level by binding to the 3′-untranslated regions of their target mRNAs. 6,7 MiRNAs have now emerged as key regulators of cardiac growth, vascular development, and angiogenesis. 8,9 Recent studies demonstrated that miRNAs can be detected in circulating blood and may be useful as disease biomarkers. 10,11 The levels and identities of circulating miRNAs in cardiovascular diseases have been evaluated in a series of studies. For instance, levels of some vascular and inflammation-associated miRNAs were found to be significantly lower in the plasma of 67 patients with CHD when compared with controls, 12 and the cardiac-specific miRNA, miR-208a, was only detectable in 33 patients with AMI and not Background-Circulating microRNAs ( miRNAs) are emerging as novel disease biomarkers. We aimed to explore the association between circulating miRNAs and the occurrence of acute myocardial infarction (AMI) in Chinese populations. Methods and Results-In the discovery stage, the plasma of 20 patients with AMI and 20 controls were pooled respectively and profiled by massively parallel sequencing. Seventy-seven miRNAs showed differential expression. Selected miRNAs were validated in 178 patients with AMI and 198 controls using quantitative reverse transcriptase polymerase chain reaction assays and further replicated in 150 patients with AMI and 150 controls. Results suggest that miR-320b and miR-125b levels were significantly lower in patients with AMI than in controls in both validation populations (P<0.0001). Lower levels of miR-320b and miR-125b were associated with increased occurrence of AMI (adjusted odds ratio, 4.71; 95% confidence interval, 2.96-7.48 and odds ratio, 4.27; 95% confidence interval, 2.84-6.41, respectively). Addition of the 2 miRNAs to traditional risk factors led to a significant improvement in the area under the curve from 0.822 (95% confidence interval, 0.787-0.856) to 0.871 (95% confidence interval, 0.842-0.900), with a net reclassification improvement of 20.45% (P<0.0001) and an integrated discrimination improvement of 0.16 (P<0.0001) for patients with AMI. A functional study showed that miR-320b and miR-125b could regulate the expression profiles of genes enriched in several signal transduction pathways critical for coronary heart disease in human vascular endothelial cells. Conclusions-The...

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“…Intriguingly, miR‐126 attenuates the expression of CXCR4 on c‐Kit + cells situated in the bone marrow while increasing the expression of SDF‐1α in ischaemic tissues, triggering mobilization of c‐Kit + cells from the bone marrow and favouring their homing into the injured site 59, 68.…”

Section: Molecular Signatures Associated With Pc Homingmentioning

confidence: 99%

MicroRNAs; easy and potent targets in optimizing therapeutic methods in reparative angiogenesis

Pourrajab

Zarch

Hekmatimoghaddam

et al. 2015

J Cellular Molecular Medi

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The age‐related senescence of adult tissues is associated with the decreased level of angiogenic capability and with the development of a degenerative disease such as atherosclerosis which thereafter result in the deteriorating function of multiple systems. Findings indicate that tissue senescence not only diminishes repair processes but also promotes atherogenesis, serving as a double‐edged sword in the development and prognosis of ischaemia‐associated diseases. Evidence evokes microRNAs (miRNAs) as molecular switchers that underlie cellular events in different tissues. Here, miRNAs would promote new potential targets for optimizing therapeutic methods in blood flow recovery to the ischaemic area. Effectively beginning an ischaemia therapy, a more characteristic of miRNA changes in adult tissues is prerequisite and in the forefront. It may also be a preliminary phase in treatment strategies by stem cell‐based therapy.

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Delivery of MicroRNA-126 by Apoptotic Bodies Induces CXCL12-Dependent Vascular Protection

Cited by 1,195 publications

References 41 publications

MicroRNA126 contributes to granulocyte colony-stimulating factor-induced hematopoietic progenitor cell mobilization by reducing the expression of vascular cell adhesion molecule 1

MicroRNA126 contributes to granulocyte colony-stimulating factor-induced hematopoietic progenitor cell mobilization by reducing the expression of vascular cell adhesion molecule 1

Circulating MicroRNAs and the Occurrence of Acute Myocardial Infarction in Chinese Populations

MicroRNAs; easy and potent targets in optimizing therapeutic methods in reparative angiogenesis

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