Microvesicle-mediated Transfer of MicroRNA-150 from Monocytes to Endothelial Cells Promotes Angiogenesis

Li, Jing; Zhang, Yujing; Liu, Yuchen; Dai, Xin; Li, Wenyang; Cai, Xing Fu; Yin, Yuan; Wang, Qiang; Xue, Yunxing; Wang, Cheng; Li, Dameng; Hou, De‐Xing; Jiang, Xiaohong; Zhang, Junfeng; Zen, Ke; Chen, Xi; Zhang, Chenyu

doi:10.1074/jbc.m113.489302

Cited by 172 publications

(132 citation statements)

References 22 publications

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“…These findings are consistent with another study showing increased lung angiogenesis in miR-150 −/− mice in a model of oxygen-induced neonatal lung injury (29). Although these data strongly support a primarily direct effect of vascular-enriched miR-150 on endothelial function and ocular angiogenesis, we cannot rule out potential contributions from circulating miR-150, which was found in monocytederived microvesicles to regulate target genes in the recipient ECs and affect pathological angiogenesis in tumor and diabetic models (30,31). In addition, genetic variation in research mouse strains may also contribute to their observed eye phenotype, as was discovered for rd8 mutation (32), and potentially vascular phenotype.…”

Section: Discussionsupporting

confidence: 72%

Endothelial microRNA-150 is an intrinsic suppressor of pathologic ocular neovascularization

Liu

Sun

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Pathologic ocular neovascularization commonly causes blindness. It is critical to identify the factors altered in pathologically proliferating versus normally quiescent vessels to develop effective targeted therapeutics. MicroRNAs regulate both physiological and pathological angiogenesis through modulating expression of gene targets at the posttranscriptional level. However, it is not completely understood if specific microRNAs are altered in pathologic ocular blood vessels, influencing vascular eye diseases. Here we investigated the potential role of a specific microRNA, miR-150, in regulating ocular neovascularization. We found that miR-150 was highly expressed in normal quiescent retinal blood vessels and significantly suppressed in pathologic neovessels in a mouse model of oxygen-induced proliferative retinopathy. MiR-150 substantially decreased endothelial cell function including cell proliferation, migration, and tubular formation and specifically suppressed the expression of multiple angiogenic regulators, CXCR4, DLL4, and FZD4, in endothelial cells. Intravitreal injection of miR-150 mimic significantly decreased pathologic retinal neovascularization in vivo in both wild-type and miR-150 knockout mice. Loss of miR-150 significantly promoted angiogenesis in aortic rings and choroidal explants ex vivo and laser-induced choroidal neovascularization in vivo. In conclusion, miR-150 is specifically enriched in quiescent normal vessels and functions as an endothelium-specific endogenous inhibitor of pathologic ocular neovascularization.neovascularization | endothelial cells | microRNA | miR-150 | retinopathy

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Section: Discussionsupporting

confidence: 72%

Endothelial microRNA-150 is an intrinsic suppressor of pathologic ocular neovascularization

Liu

Sun

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Наоборот, эндотелиальные клетки могут быть мишенями экзогенных микроРНК, секретируемых другими клетками сосудистого русла, например, моноцитами. В результате происходит ускорение пролиферации эндотелиальных клеток из-за их обогащения miR-150 в микровезикулах моноцитарного происхождения, в частности, в образцах, полученных от пациентов с атеросклерозом [71]. Можно провести аналогию -апоптозные тельца, обогащённые miR-126, захватываются HUVECs, что приводит к регрессу атеросклеротических поражений, в результате индукции экспрессии CXCL12 через CXCR4 [72].…”

Section: использование микрорнк в диагностических целяхunclassified

Epigenetic factors in atherogenesis: microRNA

et al. 2016

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MicroRNAs (miRNAs) are small (~22 nucleotides in length) noncoding RNA sequences regulating gene expression at posttranscriptional level. MicroRNAs bind complementarily to certain mRNA and cause gene silencing. The involvement of miRNAs in the regulation of lipid metabolism, inflammatory response, cell cycle progression and proliferation, oxidative stress, platelet activation, endothelial and vascular smooth muscle cells (VSMC) function, angiogenesis and plaque formation and rapture indicates important roles in the initiation and progression of atherosclerosis. The key role of microRNAs in pathophysiology of cardiovascular diseases (CVDs), including atherosclerosis, was demonstrated in recent studies. Creating antisense oligonucleotides is a novel technique for selective changes in gene expression both in vitro and in vivo. In this review, we draw attention to the role of miRNAs in atherosclerosis progression, using miRNA as the potential biomarkers and targets in the CVDs, as well as possible application of antisense oligonucleotides

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“…Starting on the day the acute myocardial infarction was performed as described, 47 saline or exosomes derived from AngII-stimulated WT macrophages (100 or 200 mg) were injected intravenously into mir-155 À/À mice every other day for a total four injections.…”

Section: Exosome Transfusion Experimentsmentioning

confidence: 99%

Macrophage-Derived mir-155-Containing Exosomes Suppress Fibroblast Proliferation and Promote Fibroblast Inflammation during Cardiac Injury

et al. 2017

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Inflammation plays an important role in cardiac injuries. Here, we examined the role of miRNA in regulating inflammation and cardiac injury during myocardial infarction. We showed that mir-155 expression was increased in the mouse heart after myocardial infarction. Upregulated mir-155 was primarily presented in macrophages and cardiac fibroblasts of injured hearts, while pri-mir-155 was only expressed in macrophages. mir-155 was also presented in exosomes derived from macrophages, and it can be transferred into cardiac fibroblasts by macrophagederived exosomes. A mir-155 mimic or mir-155 containing exosomes inhibited cardiac fibroblast proliferation by downregulating Son of Sevenless 1 expression and promoted inflammation by decreasing Suppressor of Cytokine Signaling 1 expression. These effects were reversed by the addition of a mir-155 inhibitor. In vivo, mir-155-deficient mice showed a significant reduction of the incidence of cardiac rupture and an improved cardiac function compared with wild-type mice. Moreover, transfusion of wild-type macrophage exosomes to mir-155 À/À mice exacerbated cardiac rupture. Finally, the mir-155-deficient mice exhibited elevated fibroblast proliferation and collagen production, along with reduced cardiac inflammation in injured heart. Taken together, our results demonstrate that activated macrophages secrete mir-155-enriched exosomes and identify macrophagederived mir-155 as a paracrine regulator for fibroblast proliferation and inflammation; thus, a mir-155 inhibitor (i.e., mir-155 antagomir) has the potential to be a therapeutic agent for reducing acute myocardial-infarction-related adverse events.

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Microvesicle-mediated Transfer of MicroRNA-150 from Monocytes to Endothelial Cells Promotes Angiogenesis

Cited by 172 publications

References 22 publications

Endothelial microRNA-150 is an intrinsic suppressor of pathologic ocular neovascularization

Endothelial microRNA-150 is an intrinsic suppressor of pathologic ocular neovascularization

Epigenetic factors in atherogenesis: microRNA

Macrophage-Derived mir-155-Containing Exosomes Suppress Fibroblast Proliferation and Promote Fibroblast Inflammation during Cardiac Injury

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