Loss of Endothelial CXCR7 Impairs Vascular Homeostasis and Cardiac Remodeling After Myocardial Infarction

Hao, Huifeng; Hu, Shaoxuan; Chen, Hong; Bu, Dawei; Zhu, Liyuan; Xu, Chuansheng; Chu, Frances; Huo, Xingyu; Tang, Yue; Sun, Xiaogang; Ding, Bi-Sen; Liu, De-Pei; Hu, Shengshou; Wang, Miao

doi:10.1161/circulationaha.116.023027

Cited by 76 publications

(117 citation statements)

References 35 publications

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“…In our present study, we confirmed the similar biologic functions of CXCR7 in HRMEC by using shRNA-mediated genetic interference. Moreover, it has been reported that aberrant CXCR7 expression results in significant disruption of EC homeostatic functions, with a loss of contact inhibition and defects in endothelial barrier formation (44,45). These finding indicate that CXCR7 may be a potential target molecule for angiogenesis-dependent diseases.…”

Section: Discussionmentioning

confidence: 96%

miR‐539‐5p inhibits experimental choroidal neovascularization by targeting CXCR7

et al. 2018

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Stromal cell-derived factor-1 (SDF-1) has been previously confirmed to participate in the formation of choroidal neovascularization (CNV) via its receptor, CXC chemokine receptor (CXCR) 4; CXCR7 is a recently identified receptor for SDF-1. The molecular mechanisms and therapeutic value of CXCR7 in CNV remain undefined. In this study, experimental CNV was induced by laser photocoagulation in Brown-Norway pigmented rats, and aberrant CXCR7 overexpression was detected in the retinal pigment epithelial/choroid/sclera tissues of laser-injured eyes. Blockade of CXCR7 activation via CXCR7 knockdown or neutralizing Ab administration inhibited SDF-1-induced cell survival and the tubular formation of human retinal microvascular endothelial cells (HRMECs) in vitro and reduced CNV leakage and lesion size in vivo. By using microRNA array screening and bioinformatic analyses, we identified miR-539-5p as a regulator of CXCR7. Transfection of HRMECs and choroid-retinal endothelial (RF/6A) cells with the miR-539-5p mimic inhibited their survival and tube formation, whereas CXCR7 overexpression rescued the suppressive effect of miR-539-5p. The antiangiogenic activities of the miR-539-5p mimic were additionally demonstrated in vivo by intravitreal injection. ERK1/2 and AKT signaling downstream of CXCR7 is involved in the miR-539-5p regulation of endothelial cell behaviors. These findings suggest that the manipulation of miR-539-5p/CXCR7 levels may have important therapeutic implications in CNV-associated diseases.-Feng, Y., Wang, J., Yuan, Y., Zhang, X., Shen, M., Yuan, F. miR-539-5p inhibits experimental choroidal neovascularization by targeting CXCR7.

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Section: Discussionmentioning

confidence: 96%

miR‐539‐5p inhibits experimental choroidal neovascularization by targeting CXCR7

et al. 2018

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“…Deng et al have demonstrated that intercellular-adhesion-molecule-1-targeted microbubbles had successfully delivered the angiopoetin-1 gene to inflammatory endothelial cells and improved cardiac function of mice with myocardial infarction [25]. More recently, Hao et al reported that CXCR7, which is a chemokine receptor for CXCL12, was a key regulator for angiogenesis in the endothelium [26]. The information about transfected cells may be of value for future studies of the relationship between the therapeutic gene expression and their pharmacological effects.…”

Section: Discussionmentioning

confidence: 99%

Tissue suction-mediated gene transfer to the beating heart in mice

et al. 2020

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We previously developed an in vivo site-specific transfection method using a suction device in mice; namely, a tissue suction-mediated transfection method (tissue suction method). The aim of this study was to apply the tissue suction method for cardiac gene transfer. Naked plasmid DNA (pDNA) was intravenously injected in mice, followed by direct suction on the beating heart by using a suction device made of polydimethylsiloxane. We first examined the effects of suction conditions on transgene expression and toxicity. Subsequently, we analyzed transgene-expressing cells and the transfected region of the heart. We found that heart suction induced transgene expression, and that −75 kPa and −90 kPa of suction achieved high transgene expression. In addition, the inner diameter of the suction device was correlated with transgene expression, but the pressure hold time did not change transgene expression. Although the tissue suction method at −75 kPa induced a transient increase in the serum cardiac toxicity markers at 6 h after transfection, these markers returned to normal at 24 h. The cardiac damage was also analyzed through the measurement of hypertrophic gene expression, but no significant differences were found. In addition, the cardiac function monitored by echocardiography remained normal at 11 days after transfection. Immunohistochemical analysis revealed that CD31-positive endothelial cells coexpressed the ZsGreen1-N1 reporter gene. In conclusion, the tissue suction method can achieve an efficient and safe gene transfer to the beating heart in mice.

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“…Loss of endothelial normal function or structural integrity results in acute thrombosis, or chronic vascular changes that predispose to thrombosis among a variety of diseases, such as atherosclerosis, restenosis, diabetes mellitus, obesity, etc. [70][71][72][73] Understanding the mechanism by which endothelium regulates thrombosis not only provides insights into thrombosis mechanism and pathology of relevant diseases but also fuel the therapeutic endeavor for discovering effective antithrombotic drugs with minimal or no bleeding risk, which constitute a substantial unmet medical need.…”

Section: Discussionmentioning

confidence: 99%