16 kDa vasoinhibin binds to integrin alpha5 beta1 on endothelial cells to induce apoptosis

Many functions of vasoinhibins have been reported, but its receptor has not been clarified yet. Vasoinhibins, 11–18 kDa N-terminal fragments of prolactin, have anti-angiogenic activity and act on endothelial cells to induce apoptosis and to inhibit migration and proliferation, which are opposite to the effects of prolactin. Although vasoinhibins bind to the prolactin receptor, its binding activity is very weak compared to prolactin. Therefore, in this study, we evaluated the binding activity between 16 kDa vasoinhibin and integrin beta1, alpha5 beta1, alpha1 beta1 and alphaV beta3 to identify a specific receptor for vasoinhibins. Moreover, we examined whether 16 kDa vasoinhibin induced apoptosis through integrin beta1 and alpha5 beta1 in endothelial cells. In this study, binding assays and co-immunoprecipitation experiments demonstrated that 16 kDa vasoinhibin could bind strongly to integrin beta1 and alpha5 beta1. Moreover, neutralizing with integrin beta1 and alpha5 beta1 antibody could inhibit 16 kDa vasoinhibin-induced apoptosis in endothelial cells. These findings suggest that vasoinhibins can act on endothelial cells through integrin alpha5 beta1 to induce apoptosis.

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Inhibition of Tumor Growth by RGD Peptide Directed Delivery of Truncated Tissue Factor to the Tumor Vasculature.

Blood ◽

10.1182/blood.v104.11.1934.1934 ◽

2004 ◽

Vol 104 (11) ◽

pp. 1934-1934

Author(s):

Torsten Kessler ◽

Ralf Bieker ◽

Teresa Padro ◽

Federico Herrera ◽

Sandra Ruiz ◽

...

Keyword(s):

Endothelial Cells ◽

Fusion Protein ◽

Tumor Growth ◽

Tissue Factor ◽

Tumor Vasculature ◽

Binding Activity ◽

In Vivo Studies ◽

Binding Assays ◽

Tumor Vessels

Abstract Selective activation of blood coagulation in tumor vessels with subsequent tumor infarction is a promising anticancer strategy. To this end, a fusion protein consisting of the extracellular domain of tissue factor (truncated tissue factor, tTF) was fused to the peptide GRGDSP selectively targeting avb3 and avb5 integrins on tumor endothelial cells. The fusion protein tTF-RGD retained its thrombogenic and integrin binding activity as demonstrated by coagulation assays and binding assays with purified avb3 and endothelial cells. In vivo studies in mice bearing established human adenocarcinomas (CCL185), human melanoma (M21) and human fibrosarcoma (HT1080) revealed that i.v. administration of tTF-RGD induced partial or complete thrombotic occlusion of tumor vessels as indicated by histological analysis. Furthermore, treatment studies showed that tTF-RGD but not untargeted tTF induced significant tumor growth retardation or regression in all three types of solid tumors in mice without apparent side effects such as thrombosis in liver, kidney, heart or lung. Thus, selective thrombosis in the tumor vasculature induced by tTF-RGD may be a promising strategy for the treatment of cancer.

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P. falciparum Isolate-Specific Distinct Patterns of Induced Apoptosis in Pulmonary and Brain Endothelial Cells

PLoS ONE ◽

10.1371/journal.pone.0090692 ◽

2014 ◽

Vol 9 (3) ◽

pp. e90692 ◽

Cited By ~ 10

Author(s):

Nadine N'Dilimabaka ◽

Zacharie Taoufiq ◽

Sergine Zougbédé ◽

Serge Bonnefoy ◽

Audrey Lorthiois ◽

...

Keyword(s):

Endothelial Cells ◽

Brain Endothelial Cells ◽

Falciparum Isolate ◽

Induced Apoptosis

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Zhenbao pill attenuates hydrogen peroxide–induced apoptosis by inhibiting autophagy in human umbilical vein endothelial cells

Journal of Ethnopharmacology ◽

10.1016/j.jep.2021.114020 ◽

2021 ◽

pp. 114020

Author(s):

Yuchen Jia ◽

Xiaoxue Chen ◽

Yajing Chen ◽

Hongxia Li ◽

Xiumei Ma ◽

...

Keyword(s):

Hydrogen Peroxide ◽

Endothelial Cells ◽

Umbilical Vein ◽

Human Umbilical Vein ◽

Induced Apoptosis ◽

Umbilical Vein Endothelial Cells

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miR-181c-5p mediates apoptosis of vascular endothelial cells induced by hyperoxemia via ceRNA crosstalk

Scientific Reports ◽

10.1038/s41598-021-95712-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jizhi Wu ◽

Guangqi Zhang ◽

Hui Xiong ◽

Yuguang Zhang ◽

Gang Ding ◽

...

Keyword(s):

Endothelial Cells ◽

Oxygen Therapy ◽

Vascular Endothelial Cells ◽

Inhibitory Effect ◽

Vascular Endothelial ◽

Pulmonary Capillaries ◽

Pulmonary Capillary ◽

Capillary Endothelial Cells ◽

Nasal Inhalation ◽

Induced Apoptosis

AbstractOxygen therapy has been widely used in clinical practice, especially in anesthesia and emergency medicine. However, the risks of hyperoxemia caused by excessive O2 supply have not been sufficiently appreciated. Because nasal inhalation is mostly used for oxygen therapy, the pulmonary capillaries are often the first to be damaged by hyperoxia, causing many serious consequences. Nevertheless, the molecular mechanism by which hyperoxia injures pulmonary capillary endothelial cells (LMECs) has not been fully elucidated. Therefore, we systematically investigated these issues using next-generation sequencing and functional research techniques by focusing on non-coding RNAs. Our results showed that hyperoxia significantly induced apoptosis and profoundly affected the transcriptome profiles of LMECs. Hyperoxia significantly up-regulated miR-181c-5p expression, while down-regulated the expressions of NCAPG and lncRNA-DLEU2 in LMECs. Moreover, LncRNA-DLEU2 could bind complementarily to miR-181c-5p and acted as a miRNA sponge to block the inhibitory effect of miR-181c-5p on its target gene NCAPG. The down-regulation of lncRNA-DLEU2 induced by hyperoxia abrogated its inhibition of miR-181c-5p function, which together with the hyperoxia-induced upregulation of miR-181c-5p, all these significantly decreased the expression of NCAPG, resulting in apoptosis of LMECs. Our results demonstrated a ceRNA network consisting of lncRNA-DLEU2, miR-181c-5p and NCAPG, which played an important role in hyperoxia-induced apoptosis of vascular endothelial injury. Our findings will contribute to the full understanding of the harmful effects of hyperoxia and to find ways for effectively mitigating its deleterious effects.

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P120-Catenin Inhibits Endotoxin-Induced Apoptosis In Pulmonary Endothelial Cells

10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a2209 ◽

2012 ◽

Author(s):

Guochang Hu ◽

Yan-lei Wang ◽

Richard Minshall ◽

Zhibo Yan ◽

Asrar Malik

Keyword(s):

Endothelial Cells ◽

P120 Catenin ◽

Pulmonary Endothelial Cells ◽

Induced Apoptosis

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Ethanol inhibits monocyte chemotactic protein-1 expression in interleukin-1β-activated human endothelial cells

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00106.2005 ◽

2005 ◽

Vol 289 (4) ◽

pp. H1669-H1675 ◽

Cited By ~ 12

Author(s):

John P. Cullen ◽

Shariq Sayeed ◽

Ying Jin ◽

Nicholas G. Theodorakis ◽

James V. Sitzmann ◽

...

Keyword(s):

Endothelial Cells ◽

Umbilical Vein ◽

Binding Activity ◽

Protective Effects ◽

Monocyte Adhesion ◽

Monocyte Chemotactic Protein ◽

Chemotactic Protein ◽

Subendothelial Space ◽

Umbilical Vein Endothelial Cells

The aim of this study was to determine the effect of ethanol (EtOH) on endothelial monocyte chemotactic protein-1 (MCP-1) expression. IL-1β increased the production of MCP-1 by human umbilical vein endothelial cells from undetectable levels to ∼900 pg/ml at 24 h. EtOH dose-dependently inhibited IL-1β-stimulated MCP-1 secretion as determined by ELISA: 25 ± 1%, 35 ± 7%, and 65 ± 5% inhibition for 1, 10, and 100 mM EtOH, respectively, concomitant with inhibition of monocyte adhesion to activated endothelial cells. Similarly, EtOH dose-dependently inhibited IL-1β-stimulated MCP-1 mRNA expression. Experiments with actinomycin D demonstrated that EtOH decreased the stability of MCP-1 mRNA. In addition, EtOH significantly reduced NF-κB and AP-1 binding activity induced by IL-1β and inhibited MCP-1 gene transcription. Binding of 125I-labeled MCP-1 to its receptor (CCR2) on THP-1 human monocytic cells was not affected by EtOH treatment. Modulation of the expression of MCP-1 represents a mechanism whereby EtOH could inhibit atherogenesis by blocking the crucial early step of monocyte adhesion and subsequent recruitment to the subendothelial space. These actions of EtOH may underlie, in part, its cardiovascular protective effects in vivo.

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NEAT1/miR-140-3p/MAPK1 mediates the viability and survival of coronary endothelial cells and affects coronary atherosclerotic heart disease

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmaa087 ◽

2020 ◽

Vol 52 (9) ◽

pp. 967-974

Author(s):

Hui Zhang ◽

Ningning Ji ◽

Xinyan Gong ◽

Shimao Ni ◽

Yu Wang

Keyword(s):

Cell Proliferation ◽

Endothelial Cells ◽

Heart Disease ◽

Cell Viability ◽

Mitogen Activated Protein Kinase ◽

Expression Level ◽

Luciferase Reporter ◽

Coronary Endothelial Cells ◽

Induced Apoptosis ◽

Lncrna Neat1

Abstract Studies have shown that long non-coding RNAs (lncRNA) play critical roles in coronary atherosclerotic heart disease (CAD). However, the function of lncRNA nuclear enriched abundant transcript 1 (NEAT1) in CAD is unclear. In this study, we aimed to investigate the functions of lncRNA NEAT1 in CAD. RT-PCR and western blot analysis were carried out to examine the expressions of related RNAs. Colony formation assay, cell proliferation assay, apoptosis assay, and dual-luciferase reporter assay were conducted to investigate the abilities of colony migration, cell proliferation, apoptosis, and targeting. The results showed that NEAT1 was up-regulated in CAD blood samples and in human coronary endothelial cells (HCAECs). Transfection of pcNEAT1 significantly inhibited the survival rate of HCAECs and induced apoptosis of HCAECs. MiR-140-3p was down-regulated in HCAECs. NEAT1 directly targeted miR-140-3p, and the expression of miR-140-3p was inversely correlated with the expression of NEAT1 in CAD patients. In addition, co-transfection of NEAT1 with miR-140-3p mimic reversed the effect of pcNEAT1 on cell viability and apoptosis. mitogen-activated protein kinase 1 (MAPK1) was proved to be a target gene of miR-140-3p, and the miR-140-3p mimic was shown to reduce the expression of MAPK1 in HCAECs. pcNEAT1 significantly increased the expression level of MAPK1, while shNEAT1 significantly reduced the expression level of MAPK1. Our results revealed that lncRNA NEAT1 increased cell viability and inhibited CAD cell apoptosis possibly by activating the miR-140-3p/MAPK1 pathway, and lncRNA NEAT1 might serve as a potential therapeutic target for CAD.

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