Coronary Serum Exosomes Derived from Patients with Myocardial Ischemia Regulate Angiogenesis through the miR-939-mediated Nitric Oxide Signaling Pathway

Li, Hao; Liao, Yiteng; Gao, Lei; Zhuang, Tao; Huang, Zheyong; Zhu, Hongming; Ge, Junbo

doi:10.7150/thno.21895

Cited by 106 publications

(96 citation statements)

References 37 publications

(49 reference statements)

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“…House et al proposed that without affecting the cardiac hypertrophic response, activation of FGFR1 and FGFR2 in endothelial cells could increase vessel density and improve cardiac functional recovery and vascular remodelling in a cardiac ischaemia‐reperfusion injury model, suggesting a therapeutic benefit from the activation of endothelial FGFR pathways . Recent research has found that coronary serum exosomes could regulate angiogenesis through the miR‐939‐mediated nitric oxide signalling pathway in myocardial ischaemia patients . Many signalling pathways mediated by exosomal miRNAs are involved in cardiac injury and rehabilitation.…”

Section: Discussionmentioning

confidence: 99%

“…47 Recent research has found that coronary serum exosomes could regulate angiogenesis through the miR-939-mediated nitric oxide signalling pathway in myocardial ischaemia patients. 48 Many signalling pathways mediated by exosomal miRNAs are involved in cardiac injury and rehabilitation. Further functional exploration might help us to understand their complicated mechanisms.…”

Section: Discussionmentioning

confidence: 99%

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Exosomal miRNAs as potential biomarkers for acute myocardial infarction

et al. 2019

IUBMB Life

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microRNAs (miRNAs) can be used as biomarkers for acute myocardial infarction (AMI). However, few reports have focused on the value of exosomal miRNAs in the mechanism of the pathophysiological process from stable coronary artery disease (SCAD) to AMI. Exosomes were isolated via ultracentrifugation after serum samples were collected. The exosomes were then identified by transmission electron microscopy, western blotting, and nanoparticle tracking analysis. The differential expression of miRNAs in exosomes from six AMI and six matching SCAD patients was screened using the Agilent Human miRNA Microarray Kit. Target genes of the candidate miRNAs were predicted via an online miRNA database, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes analyses. Further validation was conducted through quantitative real‐time polymerase chain reaction with 60 exosome samples. The expression of 13 miRNAs was significantly downregulated in the AMI samples compared with the SCAD samples. In addition, we identified various target genes that are mainly involved in the pathways of cardiac rehabilitation and remodelling. Validation of the expression of candidate miRNAs indicated that exosomal miR‐1915‐3p, miR‐4,507, and miR‐3,656 were significantly less expressed in AMI samples than in SCAD samples, and area under the receiver‐operating‐characteristic curve (AUC) analysis showed that the expression of these miRNAs resulted in good predictive accuracy [miR‐1915‐3p (AUC: 0.772); miR‐4,507 (AUC: 0.684); and miR‐3,656 (AUC: 0.771)], suggesting that these serum exosomal miRNAs might be predictive for AMI at an early stage. Hence, exosomal miRNAs might play an important role in the pathophysiology of AMI and could serve as diagnostic biomarkers.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Exosomal miRNAs as potential biomarkers for acute myocardial infarction

et al. 2019

IUBMB Life

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“…Exosomes originated from introverted budding of cytoplasmic multivesicles and were released by fusion of multivesicles and cell membranes (24). In recent days, there has been a growing interest in stress-induced exosomes and the association between their release and several pathologic conditions (25).…”

Section: Exosomes Are Internalized By Vascular Endothelial Cellsmentioning

confidence: 99%

Down‐regulation of exosomal microRNA‐224‐3p derived from bone marrow–derived mesenchymal stem cells potentiates angiogenesis in traumatic osteonecrosis of the femoral head

Liao

Liu

et al. 2019

FASEB j.

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Traumatic osteonecrosis of the femoral head (ONFH) is a condition leading to the collapse of the femoral head, and the primary treatment is a total hip replacement, which has a poor prognosis. The current study was conducted with the aim of investigating the role of exosomes from bone marrow‐derived mesenchymal stem cells (BM‐MSCs) carrying microRNA‐224‐3p (miR‐224‐3p) in traumatic ONFH. Initially, a microarray analysis was performed to screen the differentially expressed genes and miRs associated with traumatic ONFH. Patients with traumatic and nontraumatic ONFH were enrolled, and HUVECs were obtained. The BM‐MSCs‐derived exosomes were purified and characterized, after which HUVECs were cocultured with exosomes. The functional role of miR‐224‐3p in traumatic ONFH was determined using ectopic expression, depletion, and reporter assay experiments. Endothelial cell proliferation, migration, invasion abilities, and angiogenesis were evaluated. Based on microarray analysis, miR‐224‐3p was found to be down‐regulated, whereas focal adhesion kinase family interacting protein of 200 kDa (FIP200) was up‐regulated in ONFH. Traumatic ONFH exosomes resulted in the up‐regulation of FIP200 and down‐regulation of miR‐224‐3p. FIP200 was confirmed to be a target gene of miR‐224‐3p. Exosomes were internalized by vascular endothelial cells. The down‐regulation of exosomal miR‐224‐3p was observed to promote endothelial cell proliferation, migration, invasion abilities, angiogenesis, and FIP200 expression. In addition, FIP200 overexpression promoted angiogenesis. In summary, the results highly indicated that lower miR‐224‐3p levels in exosomes derived from BM‐MSCs promote angiogenesis of traumatic ONFH by up‐regulating FIP200. The present study provides a potential strategy for the treatment of traumatic ONFH.—Xu, H.‐J., Liao, W., Liu, X.‐Z., Hu, J., Zou, W.‐Z., Ning, Y., Yang, Y., Li, Z.‐H. Down‐regulation of exosomal microRNA‐224‐3p derived from bone marrow‐derived mesenchymal stem cells potentiates angiogenesis in traumatic osteonecrosis of the femoral head. FASEB J. 33, 8055–8068 (2019). http://www.fasebj.org

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“…Instead of pericardial fluid, Li et al [64] investigated the angiogenic effects of coronary serum exosomes isolated from patients with myocardial ischemia on endothelial cells like HUVECs. In vitro testing revealed significantly higher endothelial cell migration, proliferation and tube formation following treatment with test exosomes compared to those isolated from normal individuals.…”

Section: Exosomes In Cardiovascular Diseasementioning

confidence: 99%

Exosomes: Biological Couriers with Transformative Messages

Yousef¹,

Abdelnaser²

2019

J. Biomed

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Exosomes are nanovesicles produced by almost all cell types to the extracellular environment. These structures, initially mistaken for "cellular dust", are key effectors of cell-cell communication and play major roles in maintaining normal physiological function and homeostatic balance as well as relaying pathology. Given their non-immunogenicity, their native membrane composition combined with the wealth of contained bioinfomative cargoes and coupled to their innate ability to cross multiple biological barriers, these tiny sacs have merited a great deal of interest in recent years and are slowly edging their way to the surface. Accruing evidence corroborating the far-reaching potential of exosomes is ever growing and easily demonstrable. Nonetheless, progress with translation of the reported outcomes to clinical settings and recognition of these tools as a multi-application platform remains much too inadequate for the outstanding potential of these biological messengers and the entailed shift in theragnostic paradigms. The purpose of this review is to recapitulate on the most recent advances in exosome research and accentuate their momentous promise as game changers in disease diagnostics and therapeutics. Finally, market transition and commercialization efforts are highlighted with a brief commentary on the status quo. Syndecans/syntenin system: Syndecans are membrane-associated proteoglycans, whereas syntenin is a syndecan-interacting protein. Syntenin contains a PDZ domain, which constitutes the site of interaction with syndecan. The syndecan/syntenin system has been proven to play a key role in exosomal biogenesis [98]. 4Cortactin: a protein involved in cytoskeletal modification.

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Coronary Serum Exosomes Derived from Patients with Myocardial Ischemia Regulate Angiogenesis through the miR-939-mediated Nitric Oxide Signaling Pathway

Cited by 106 publications

References 37 publications

Exosomal miRNAs as potential biomarkers for acute myocardial infarction

Exosomal miRNAs as potential biomarkers for acute myocardial infarction

Down‐regulation of exosomal microRNA‐224‐3p derived from bone marrow–derived mesenchymal stem cells potentiates angiogenesis in traumatic osteonecrosis of the femoral head

Exosomes: Biological Couriers with Transformative Messages

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