scholarly journals A Protective Role of Paeoniflorin in Fluctuant Hyperglycemia-Induced Vascular Endothelial Injuries through Antioxidative and Anti-Inflammatory Effects and Reduction of PKCβ1

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Jing-Shang Wang ◽  
Ye Huang ◽  
Shuping Zhang ◽  
Hui-Jun Yin ◽  
Lei Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Level ◽  
Umbilical Vein ◽  
Protective Role ◽  
Vascular Endothelial ◽  
Glucose Levels ◽  
Umbilical Vein Endothelial Cells

Hyperglycemia fluctuation is associated with diabetes mellitus (DM) complications when compared to persistent hyperglycemia. Previous studies have shown that paeoniflorin (PF), through its antiapoptosis, anti-inflammation, and antithrombotic properties, effectively protects against cardiovascular and cerebrovascular disease. However, the mechanism underlying the protection from PF against vascular injuries induced by hyperglycemia fluctuations remains poorly understood. Herein, we investigated the potential protective role of PF on human umbilical vein endothelial cells (HUVECs) subjected to intermittent glucose levels in vitro and in DM rats with fluctuating hyperglycemia in vivo. A remarkable increased apoptosis associated with elevated inflammation, increased oxidative stress, and high protein level of PKCβ1 was induced in HUVECs by intermittently changing glucose for 8 days, and PF recovered those detrimental changes. LY333531, a potent PKCβ1 inhibitor, and metformin manifested similar effects. Additionally, in DM rats with fluctuating hyperglycemia, PF protected against vascular damage as what has been observed in vitro. Taken together, PF attenuates the vascular injury induced by fluctuant hyperglycemia through oxidative stress inhibition, inflammatory reaction reduction, and PKCβ1 protein level repression, suggesting its perspective clinical usage.

scholarly journals SiRNA Directed Against Annexin II Receptor Inhibits Angiogenesis via Suppressing MMP2 and MMP9 Expression

2015 ◽  
Vol 35 (3) ◽  
pp. 875-884 ◽  
Author(s):  
Hongyuan Song ◽  
Dongyan Pan ◽  
Weifeng Sun ◽  
Cao Gu ◽  
Yuelu Zhang ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Annexin Ii ◽  
Mmp9 Expression ◽  
Cell Arrest ◽  
Umbilical Vein Endothelial Cells

Background/Aims: Annexin II receptor (AXIIR) is able to mediate Annexin II signal and induce apoptosis, but its role in angiogenesis remains unclear. This study tries to investigate the role of AXIIR in angiogenesis and the plausible molecular mechanism. Methods/Results: RNA interference technology was used to silence AXIIR, and the subsequent effects in vitro and in vivo were evaluated thereafter. Our data indicated that human umbilical vein endothelial cells (HUVECs) expressed AXIIR and knockdown of AXIIR significantly inhibited HUVECs proliferation, adhesion, migration, and tube formation in vitro and suppressed angiogenesis in vivo. Furthermore, AXIIR siRNA induced cell arrest in the S/G2 phase while had no effect on cell apoptosis. We found that these subsequent effects might be via suppressing the expression of matrix metalloproteinase 2and matrix metalloproteinase 9. Conclusion: AXIIR participates in angiogenesis, and may be a potential therapeutic target for angiogenesis related diseases.

scholarly journals Double-edged effects caused by magnesium ions and alkaline environment regulate bioactivities of magnesium-incorporated silicocarnotite in vitro

2021 ◽  
Vol 8 (6) ◽  
Author(s):  
Qiang Wu ◽  
Shunxiang Xu ◽  
Fei Wang ◽  
Bo He ◽  
Xin Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Umbilical Vein ◽  
Alkaline Condition ◽  
Akt Signaling Pathway ◽  
Alkaline Environment ◽  
Umbilical Vein Endothelial Cells ◽  
Adverse Factor

Abstract Magnesium (Mg) is an important element for its enhanced osteogenic and angiogenic properties in vitro and in vivo, however, the inherent alkalinity is the adverse factor that needs further attention. In order to study the role of alkalinity in regulating osteogenesis and angiogenesis in vitro, magnesium-silicocarnotite [Mg-Ca5(PO4)2SiO4, Mg-CPS] was designed and fabricated. In this study, Mg-CPS showed better osteogenic and angiogenic properties than CPS within 10 wt.% magnesium oxide (MgO), since the adversity of alkaline condition was covered by the benefits of improved Mg ion concentrations through activating Smad2/3-Runx2 signaling pathway in MC3T3-E1 cells and PI3K-AKT signaling pathway in human umbilical vein endothelial cells in vitro. Besides, provided that MgO was incorporated with 15 wt.% in CPS, the bioactivities had declined due to the environment consisting of higher-concentrated Mg ions, stronger alkalinity and lower Ca/P/Si ions caused. According to the results, it indicated that bioactivities of Mg-CPS in vitro were regulated by the double-edged effects, which were the consequence of Mg ions and alkaline environment combined. Therefore, if MgO is properly incorporated in CPS, the improved bioactivities could cover alkaline adversity, making Mg-CPS bioceramics promising in orthopedic clinical application for its enhancement of osteogenesis and angiogenesis in vitro.

scholarly journals Dasatinib increases endothelial permeability leading to pleural effusion

2018 ◽  
Vol 51 (1) ◽  
pp. 1701096 ◽  
Author(s):  
Carole Phan ◽  
Etienne-Marie Jutant ◽  
Ly Tu ◽  
Raphaël Thuillet ◽  
Andrei Seferian ◽  
...  
Keyword(s):  
Pleural Effusion ◽  
Kinase Inhibitor ◽  
Umbilical Vein ◽  
Endothelial Permeability ◽  
Cell Junctions ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Umbilical Vein Endothelial Cells

Pleural effusion is a frequent side-effect of dasatinib, a second-generation tyrosine kinase inhibitor used in the treatment of chronic myelogenous leukaemia. However, the underlying mechanisms remain unknown. We hypothesised that dasatinib alters endothelial integrity, resulting in increased pulmonary vascular endothelial permeability and pleural effusion.To test this, we established the first animal model of dasatinib-related pleural effusion, by treating rats with a daily regimen of high doses of dasatinib (10 mg·kg−1·day−1 for 8 weeks).Pleural ultrasonography revealed that rats chronically treated with dasatinib developed pleural effusion after 5 weeks. Consistent with these in vivo observations, dasatinib led to a rapid and reversible increase in paracellular permeability of human pulmonary endothelial cell monolayers as reflected by increased macromolecule passage, loss of vascular endothelial cadherin and zonula occludens-1 from cell–cell junctions, and the development of actin stress fibres. These results were replicated using human umbilical vein endothelial cells and confirmed by decreased endothelial resistance. Interestingly, we demonstrated that this increased endothelial permeability is a reactive oxygen species (ROS)-dependent mechanism in vitro and in vivo using a cotreatment with an antioxidant agent, N-acetylcysteine.This study shows that dasatinib alters pulmonary endothelial permeability in a ROS-dependent manner in vitro and in vivo leading to pleural effusion.

The lymphangiogenic factor CCBE1 promotes angiogenesis and tumor growth in colorectal cancer

2021 ◽  
Vol 21 ◽  
Author(s):  
Wenjun Ding ◽  
Wenfang Tang ◽  
Jiajun Zhi
Keyword(s):  
Colorectal Cancer ◽  
Tumor Growth ◽  
Calcium Binding ◽  
Umbilical Vein ◽  
Colorectal Cancer Cell Line ◽  
Vascular Endothelial ◽  
Factor C

Background: Collagen and calcium-binding EGF domain-1 (CCBE1) is essential for the development of the lymphatic vasculature and colorectal cancer (CRC) lymphangiogenesis as it enhances the proteolytic process of vascular endothelial growth factor C (VEGFC) activating VEGFR3. The fully processed mature VEGFC could also activate VEGFR2, the important endothelial-specific receptor tyrosine kinase, involved in blood vascular development and tumor angiogenesis. However, the role of CCBE1 in cancer angiogenesis remains undefined. Methods: In this paper, we find that the protein expression of CCBE1 is higher in the primary CRC tissue with distant metastasis and positively correlated with blood vessel density. Results: The mRNA expression of CCBE1 is closely positively correlated with the vascular endothelial marker CD31 and VEGFR2 in CRC from TCGA datasets. The supernatant of the colorectal cancer cell line HCT116 with CCBE1 overexpression significantly promotes the tube formation ability of the human umbilical vein endothelial cells (HUVECs) in vitro and enhances angiogenesis and tumor growth in vivo. Knockdown of CCBE1 decreases the angiogenic ability of CRC. Conclusion: Our results demonstrate the angiogenic role of CCBE1 in CRC.

An In Vitro Toxicity Assay for Human Endothelial Cells

1988 ◽  
Vol 16 (1) ◽  
pp. 38-41
Author(s):  
Rosella Sbarbati ◽  
Maria Luisa Schinetti ◽  
Maria Scarlattini
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Umbilical Vein ◽  
Vascular Diseases ◽  
In Vitro Toxicity ◽  
Human Endothelial Cells ◽  
Experimental Conditions ◽  
Umbilical Vein Endothelial Cells

Cultured human endothelial cells can replace living animals in studying the toxic role of noxious agents in the pathogenesis of vascular diseases and in the elucidation of the mechanism of action of protective drugs. Preliminary data are presented which examine the effects that oxidative stress produces on human endothelial cells in vitro. Human umbilical vein endothelial cells were subjected to an anoxia-re-oxygenation treatment and tested for the production of Super Oxide Dismutase (SOD)-inhibitable superoxide radicals. The results show that under our experimental conditions endothelial cells produce oxygen-free radicals and that the generation reaches a maximum after an anoxic challenge of 20 minutes. We conclude that the in vitro system presented in this paper could be a suitable tool for further studies on the effects of oxidative stress on the vascular endothelium, which mimics the in vivo conditions of re-perfusion after heart ischemia.

scholarly journals Exosomal miR-3682-3p Suppresses Angiogenesis by Targeting ANGPT1 via the RAS-MEK1/2-ERK1/2 Pathway in Hepatocellular Carcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Shuang-Shuang Dong ◽  
Dan-Dan Dong ◽  
Zhang-Fu Yang ◽  
Gui-Qi Zhu ◽  
Dong-Mei Gao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Endothelial Cells ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Transmission Electron ◽  
Umbilical Vein Endothelial Cells ◽  
Hcc Cells

BackgroundAngiogenesis is a crucial process in tumorigenesis and development. The role of exosomes derived from hepatocellular carcinoma (HCC) cells in angiogenesis has not been clearly elucidated.Methods and ResultsExosomes were isolated from HCC cell lines (HCCLM3, MHCC97L, and PLC/RFP/5) by ultracentrifugation and identified by nano transmission electron microscopy (TEM), NanoSight analysis and western blotting, respectively. In vitro and in vivo analyses showed that exosomes isolated from highly metastatic HCC cells enhanced the migration, invasion and tube formation of human umbilical vein endothelial cells (HUVECs) compared to exosomes derived from poorly metastatic HCC cells. In addition, microarray analysis of HCC-Exos was conducted to identify potential functional molecules, and miR-3682-3p expression was found to be significantly downregulated in exosomes isolated from highly metastatic HCC cells. By in vitro gain-of-function experiments, we found that HCC cells secreted exosomal miR-3682-3p, which negatively regulates angiopoietin-1 (ANGPT1), and this led to inhibition of RAS-MEK1/2-ERK1/2 signaling in endothelial cells and eventually impaired angiogenesis.ConclusionOur study elucidates that exosomal miR-3682-3p attenuates angiogenesis by targeting ANGPT1 through RAS-MEK1/2-ERK1/2 signaling and provides novel potential targets for liver cancer therapy.

Abstract 462: Cardiac-specific LMCD1/dyxin-knockout in Mice Blunts Pressure Overload-induced Activation of Calcineurin Signaling

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Lucia S Kilian ◽  
Jakob Voran ◽  
Nesrin Schmiedel ◽  
Katharina Stiebeling ◽  
Julika Richter ◽  
...  
Keyword(s):  
Protein Level ◽  
Heart Function ◽  
Pressure Overload ◽  
Protective Role ◽  
Left Ventricular ◽  
Cardiomyocyte Hypertrophy ◽  
Mrna Levels

We and others have shown that LMCD1 expression levels are upregulated in various in vitro and in vivo models of hypertrophy and that LMCD1 is necessary and sufficient to induce cardiomyocyte hypertrophy in vitro . We successfully generated a new mouse line with a conditional cardiac knockout of LMCD1. We performed echocardiographic, morphometric, and molecular analysis in these LMCD1-deficient and appropriate control-mice under basic conditions as well as 14 days after transverse aortic banding (TAC)-induced left ventricular (LV) pressure overload. Our aim was to investigate the hypothesis of potential beneficial effects of LMCD1-downregulation in vivo . These knockout (KO)-mice revealed under basic conditions a significant reduction of LMCD1 in the heart to <10% on protein level compared to control (WT)-mice (females and males n=5 each, p<0.001), while anatomic and functional parameters of the heart as well as LMCD1 levels in all other tested organs remained unchanged. Sham-operated KO-mice also showed significantly reduced level of LMCD1 in the LV compared to Sham-operated WT-mice (protein level <20%, p<0.001, n=8). No significant increase of LMCD1 in TAC- compared to Sham-operated KO-mice was found. TAC-operated KO-mice showed no significant differences in heart anatomy and function when compared to TAC-operated WT-mice. However, we determined a consistent trend toward improved heart function (ejection fraction and fractional shortening). Furthermore, TAC-operated KO-mice showed reduced activation of the fetal gene program in LV-tissue compared to TAC-operated WT-mice: mRNA levels of the hypertrophic markers NppA, NppB, and Rcan1-4 were all decreased (WT-TAC n=8 vs. KO-TAC n=10: NppA 8.5±2.0 vs. 5.1±1.5, p<0.05; NppB 1.9±0.2 vs. 1.7±0.3, p=0.093; Rcan1-4 6.0±0.2 vs. 3.2 vs. 0.7, p<0.05), suggesting a protective role of LMCD1-knockout. The reduction of calcineurin (CnA)-responsive Rcan1-4 specifically suggests a protective role of LMCD1-knockout in CnA-dependent signaling. Taken together, our preliminary data reveals protective effects of LMCD1-knockout against TAC-induced hypertrophic signaling. Ongoing experiments focus on effects of LMCD1-knockout on apoptosis and fibrosis and its role in Angiotensin-induced hypertrophy.

Sign in / Sign up

Export Citation Format

Share Document