scholarly journals Hypochlorite-Modified Albumin Upregulates ICAM-1 Expressionviaa MAPK–NF-κB Signaling Cascade: Protective Effects of Apocynin

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Dong-dong Tang ◽  
Hong-xin Niu ◽  
Fen-fen Peng ◽  
Hai-bo Long ◽  
Zong-rui Liu ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Umbilical Vein ◽  
Vascular Inflammation ◽  
Specific Inhibitor ◽  
Dependent Manner ◽  
Protective Effects ◽  
Signal Cascade ◽  
Intracellular Signal ◽  
Umbilical Vein Endothelial Cells ◽  
Dose Dependent

Hypochlorite-modified albumin (HOCl-alb) has been linked to endothelial dysfunction, which plays an important role in the development of hypertension, diabetes, and chronic kidney disease. However, whether HOCl-alb induces endothelial dysfunctionviavascular inflammation and whether a signaling pathway is involved are unknown and have not been investigated. HOCl-alb was found to upregulate ICAM-1 expression in human umbilical vein endothelial cells (HUVECs) in a time- and dose-dependent manner. HOCl-alb time-dependently phosphorylated ERK1/2 andp38MAPK. HOCl-alb also activated NF-κB. ICAM-1 expression was dose-dependently inhibited by U0126 (a specific inhibitor of MEK1/2, a signal upstream from ERK1/2), SB203580 (a specific inhibitor ofp38MAPK), and SN50 (a specific inhibitor of NF-κB). U0126 and SB203580 both counteracted the activation of NF-κB, whereas the phosphorylation of ERK1/2 andp38MAPKwas not blocked by SN50. ERK1/2 phosphorylation was blocked by U0126 but not by SB203580, andp38MAPKactivity was reduced by SB203580 but not by U0126. Apocynin, a specific NADPH oxidase (NOX) inhibitor, inhibited ICAM-1 expression and the activity of ERK1/2,p38MAPK, and NF-κB. These results indicate that HOCl-alb-induced ICAM-1 expression is caused by the activation of a redox-sensitive intracellular signal cascade involving ERK1/2 andp38MAPK, culminating in the activation of NF-κB and involving NOXs among the upstream signals.

scholarly journals Sanguis draconis, a Dragon’s Blood Resin, Attenuates High Glucose-Induced Oxidative Stress and Endothelial Dysfunction in Human Umbilical Vein Endothelial Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Yi Chang ◽  
Ting-Chen Chang ◽  
Jie-Jen Lee ◽  
Nen-Chung Chang ◽  
Yung-Kai Huang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
High Glucose ◽  
Umbilical Vein ◽  
Vascular Inflammation ◽  
Dependent Manner ◽  
Dragon’S Blood ◽  
Umbilical Vein Endothelial Cells ◽  
Parp 1

Hyperglycaemia, a characteristic feature of diabetes mellitus, induces endothelial dysfunction and vascular complications by limiting the proliferative potential of these cells. Here we aimed to investigate the effect of an ethanolic extract ofSanguis draconis(SD), a kind of dragon’s blood resin that is obtained fromDaemonorops draco(Palmae), on human umbilical vein endothelial cells (HUVEC) under high-glucose (HG) stimulation and its underlying mechanism. Concentration-dependent (0–50 μg/mL) assessment of cell viability showed that SD does not affect cell viability with a similar trend up to 48 h. Remarkably, SD (10–50 μg/mL) significantly attenuated the high-glucose (25 and 50 mM) induced cell toxicity in a concentration-dependent manner. SD inhibited high glucose-induced nitrite (NO) and lipid peroxidation (MDA) production and reactive oxygen species (ROS) formation in HUVEC. Western blot analysis revealed that SD treatments abolished HG-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK 1/2), nuclear transcription factor,κB (NF-κB), VCAM-1, and E-selectin, and it also blocked the breakdown of PARP-116 kDa protein in a dose-dependent manner. Furthermore, we found that SD increased the expression of Bcl-2 and decreased Bax protein expression in HG-stimulated HUVEC. Thus, these results of this study demonstrate for the first time that SD inhibits glucose induced oxidative stress and vascular inflammation in HUVEC by inhibiting the ERK/NF-κB/PARP-1/Bax signaling cascade followed by suppressing the activation of VCAM-1 and E-selectin. These data suggest that SD may have a therapeutic potential in vascular inflammation due to the decreased levels of oxidative stress, apoptosis, and PARP-1 activation.

scholarly journals Dihydromyricetin Attenuates TNF-α-Induced Endothelial Dysfunction through miR-21-Mediated DDAH1/ADMA/NO Signal Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Dafeng Yang ◽  
Shenglan Tan ◽  
Zhousheng Yang ◽  
Pei Jiang ◽  
Caie Qin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Umbilical Vein ◽  
Underlying Mechanism ◽  
Tube Formation ◽  
Signal Pathway ◽  
Dependent Manner ◽  
Necrosis Factor Alpha ◽  
Atherosclerotic Process ◽  
Umbilical Vein Endothelial Cells

Accumulating studies demonstrate that dihydromyricetin (DMY), a compound extracted from Chinese traditional herb, Ampelopsis grossedentata, attenuates atherosclerotic process by improvement of endothelial dysfunction. However, the underlying mechanism remains poorly understood. Thus, the aim of this study is to investigate the potential mechanism behind the attenuating effects of DMY on tumor necrosis factor alpha- (TNF-α-) induced endothelial dysfunction. In response to TNF-α, microRNA-21 (miR-21) expression was significantly increased in human umbilical vein endothelial cells (HUVECs), in line with impaired endothelial dysfunction as evidenced by decreased tube formation and migration, endothelial nitric oxide synthase (eNOS) (ser1177) phosphorylation, dimethylarginine dimethylaminohydrolases 1 (DDAH1) expression and metabolic activity, and nitric oxide (NO) concentration as well as increased asymmetric dimethylarginine (ADMA) levels. In contrast, DMY or blockade of miR-21 expression ameliorated endothelial dysfunction in HUVECs treated with TNF-α through downregulation of miR-21 expression, whereas these effects were abolished by overexpression of miR-21. In addition, using a nonspecific NOS inhibitor, L-NAME, also abrogated the attenuating effects of DMY on endothelial dysfunction. Taken together, these data demonstrated that miR-21-mediated DDAH1/ADMA/NO signal pathway plays an important role in TNF-α-induced endothelial dysfunction, and DMY attenuated endothelial dysfunction induced by TNF-α in a miR-21-dependent manner.

scholarly journals Ethyl Acetate Fraction of Teucrium Polium Extract Abolishes Human Umbilical Vein Endothelial Cells (HUVEC) Tubulogenesis in Collagen Bed through Suppression of Cell Proliferation/VEGF Secretion

2019 ◽  
Author(s):  
Vahide Askari ◽  
Somayeh Shamlou ◽  
Ali Mostafaie ◽  
Sara Khaleqi
Keyword(s):  
Endothelial Cells ◽  
Ethyl Acetate ◽  
Umbilical Vein ◽  
Ethyl Acetate Fraction ◽  
Dependent Manner ◽  
Angiogenic Effect ◽  
Teucrium Polium ◽  
Umbilical Vein Endothelial Cells ◽  
Dose Dependent

Angiogenesis has essential role in growth and metastasis of tumors. Development of therapies aimed to suppress angiogenesis using medicinal plants is one of the effective approaches for prevention/treatment of cancer. The current study was performed to investigate in vitro anti-angiogenic effect of Teucrium Polium (TP) extract and its fractions. The aerial part of Teucrium Polium was powdered and extracted with 50% ethanol. The extract was fractionated in to aqueous (AQ), n-butanol (BU), ethyl acetate (EA) and n-hexane (HE) fractions. Anti-angiogenic effect of TP was examined on human umbilical vein endothelial cells (HUVECs) in three-dimensional collagen matrix. The endothelial cells form capillary-like branches that can be visualized using phase contrast microscope and the number of tube-like structures can be quantified as a measure of in vitro angiogenesis. Furthermore, anti-proliferative and vascular endothelial growth factor(VEGF )suppressive effect of TP as important factors in the process of angiogenesis were assessed using3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT)and quantitative ELISA, respectively. Based on our findings, among the TP fractions, EA fraction showed the highest inhibitory activity on angiogenesis. This fraction with IC50: 68 µg/mL, inhibited angiogenesis at 60 µg/mL. The crude extract and other fractions of TP inhibited angiogenesis in a dose-dependent manner at doses higher concentrations than EA fraction, significantly.TP extract and EA fraction were able to inhibit proliferation of HUVEC and inhibited VEGF secretion in a dose dependent manner. The ethyl acetate fraction at 60 µg/ml inhibited VEGF secretion perfectly. Our data indicated that ethyl acetate fraction of Teucrium Polium could be a potential candidate for the prevention of angiogenesis in cancer and other related disorders. However, this suggestion needs more quantitative and in vivo investigations for confirmation.

scholarly journals Tongxinluo Prevents Endothelial Dysfunction Induced by Homocysteine ThiolactoneIn Vivovia Suppression of Oxidative Stress

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Yi Zhang ◽  
Tiecheng Pan ◽  
Xiaoxuan Zhong ◽  
Cai Cheng
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Ex Vivo ◽  
Umbilical Vein ◽  
Protective Effects ◽  
Sod Activity ◽  
Homocysteine Thiolactone ◽  
Beneficial Effects ◽  
Umbilical Vein Endothelial Cells

Aim. To explore whether Chinese traditional medicine, tongxinluo (TXL), exerts beneficial effects on endothelial dysfunction induced by homocysteine thiolactone (HTL) and to investigate the potential mechanisms.Methods and Results. Incubation of cultured human umbilical vein endothelial cells with HTL (1 mM) for 24 hours significantly reduced cell viabilities assayed by MTT, and enhanced productions of reactive oxygen species. Pretreatment of cells with TXL (100, 200, and 400 μg/mL) for 1 hour reversed these effects induced by HTL. Further, coincubation with GW9662 (0.01, 0.1 mM) abolished the protective effects of TXL on HTL-treated cells. Inex vivoexperiments, exposure of isolated aortic rings from rats to HTL (1 mM) for 1 hour dramatically impaired acetylcholine-induced endothelium-dependent relaxation, reduced SOD activity, and increased malondialdehyde content in aortic tissues. Preincubation of aortic rings with TXL (100, 200, and 400 μg/mL) normalized the disorders induced by HTL. Importantly, all effects induced by TXL were reversed by GW9662.In vivoanalysis indicated that the administration of TXL (1.0 g/kg/d) remarkably suppressed oxidative stress and prevented endothelial dysfunction in rats fed with HTL (50 mg/kg/d) for 8 weeks.Conclusions. TXL improves endothelial functions in rats fed with HTL, which is related to PPARγ-dependent suppression of oxidative stress.

scholarly journals Activation of Yes-Associated Protein/PDZ-Binding Motif Pathway Contributes to Endothelial Dysfunction and Vascular Inflammation in AngiotensinII Hypertension

2021 ◽  
Vol 12 ◽  
Author(s):  
Qian Xu ◽  
Kunping Zhuo ◽  
Ruiping Cai ◽  
Xiaomin Su ◽  
Lu Zhang ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Umbilical Vein ◽  
Vascular Inflammation ◽  
Binding Motif ◽  
Hippo Signaling ◽  
Umbilical Vein Endothelial Cells

Yes-associated protein (YAP) and its associated coactivator of PDZ-binding motif (TAZ) are co-transcriptional regulators and down effectors of the Hippo signaling pathway. Recent studies have shown that the Hippo/YAP signaling pathway may play a role in mediating vascular homeostasis. This study investigated the role of YAP/TAZ in endothelial dysfunction and vascular inflammation in angiotensin (Ang)II hypertensive mice. The infusion of AngII (1.1 mg/kg/day by mini-pump) for 3 weeks induced the activation of YAP/TAZ, manifested by decreased cytosolic phosphor-YAP and phosphor-TAZ, and increased YAP/TAZ nuclear translocation, which were prevented by YAP/TAZ inhibitor verteporfin. AngII significantly increased systolic blood pressure (SBP), macrophage infiltration, and expressions of proinflammatory cytokines, and impaired endothelial function in the aorta of the mice. Treatment with verteporfin improved endothelial function and reduced vascular inflammation with a mild reduction in SBP. AngII also induced YAP/TAZ activation in human umbilical vein endothelial cells in vitro, which were prevented by LB-100, an inhibitor of protein phosphatase 2A (PP2A, a major dephosphorylase). Treatment with LB-100 reversed AngII-induced proinflammatory cytokine expression and impairment of phosphor-eNOS expression in vitro. Our results suggest that AngII induces YAP/TAZ activation via PP2A-dependent dephosphorylation, which may contribute to the impairment of endothelial function and the induction of vascular inflammation in hypertension. YAP/TAZ may be a new target for hypertensive vascular injury.

scholarly journals Anti-Inflammatory Activity of Marine Ovothiol A in an In Vitro Model of Endothelial Dysfunction Induced by Hyperglycemia

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Immacolata Castellano ◽  
Pamela Di Tomo ◽  
Natalia Di Pietro ◽  
Domitilla Mandatori ◽  
Caterina Pipino ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Therapeutic Potential ◽  
Umbilical Vein ◽  
Vascular Inflammation ◽  
Cellular Systems ◽  
Inflammatory Stress ◽  
Chronic Hyperglycemia ◽  
Anti Inflammatory ◽  
Umbilical Vein Endothelial Cells

Chronic hyperglycemia is associated with oxidative stress and vascular inflammation, both leading to endothelial dysfunction and cardiovascular disease that can be weakened by antioxidant/anti-inflammatory molecules in both healthy and diabetic subjects. Among natural molecules, ovothiol A, produced in sea urchin eggs to protect eggs/embryos from the oxidative burst at fertilization and during development, has been receiving increasing interest for its use as an antioxidant. Here, we evaluated the potential antioxidative/anti-inflammatory effect of purified ovothiol A in an in vitro cellular model of hyperglycemia-induced endothelial dysfunction employing human umbilical vein endothelial cells (HUVECs) from women affected by gestational diabetes (GD) and from healthy mothers. Ovothiol A was rapidly taken up by both cellular systems, resulting in increased glutathione values in GD-HUVECs, likely due to the formation of reduced ovothiol A. In tumor necrosis factor-α-stimulated cells, ovothiol A induced a downregulation of adhesion molecule expression and decrease in monocyte-HUVEC interaction. This was associated with a reduction in reactive oxygen and nitrogen species and an increase in nitric oxide bioavailability. These results point to the potential antiatherogenic properties of the natural antioxidant ovothiol A and support its therapeutic potential in pathologies related to cardiovascular diseases associated with oxidative/inflammatory stress and endothelial dysfunction.

Decrease of tetrahydrobiopterin and NO generation in endothelial cells exposed to simulated diving

2019 ◽  
pp. 159-169
Author(s):  
Ronja Hesthammer ◽  
◽  
Torunn Eide ◽  
Eimar Thorsen ◽  
Asbjørn M. Svardal ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Decompression Sickness ◽  
Synergistic Effects ◽  
Umbilical Vein ◽  
Bubble Formation ◽  
No Production ◽  
Dependent Manner ◽  
Hyperoxic Exposure ◽  
Umbilical Vein Endothelial Cells ◽  
Dose Dependent

Purpose: Nitric oxide (NO) has been shown to protect against bubble formation and the risk of decompression sickness. We hypothesize that oxidation of tetrahydrobiopterin (BH4) leads to a decreased production of NO during simulated diving. Methods: Human umbilical vein endothelial cells (HUVEC) were exposed to hyperoxia or simulated diving for 24 hours. The levels of biopterins (BH4, BH2 and B) were determined by LC-MS/MS, and the production of NO by monitoring the conversion of L-arginine to L-citrulline. Results: Exposure to hyperoxia decreased BH4 in a dose-dependent manner; by 48 ± 15% following exposure to 40 kPa O2 (P < 0.001 vs. control at 20 kPa O2), and 70 ± 16% following exposure to 60 kPa O2. Exposure to 40 kPa O2 decreased NO production by 25 ± 9%, but there was no further decrease when increasing oxygen exposure to 60 kPa (25 ± 10%). No additional effects of simulated diving were observed, indicating no additive or synergistic effects of hyperbaria and hyperoxia on the BH4 level or NO generation. Conclusion: NO generation in intact human endothelial cells was decreased by simulated diving, as well as by hyperoxic exposure, while BH4 levels seem to be affected only by hyperoxia. Hence, the results suggest that BH4 is not the sole determinant of NO generation in HUVEC.

Purification, molecular cloning and mechanism of action of graminelysin I, a snake-venom-derived metalloproteinase that induces apoptosis of human endothelial cells

2001 ◽  
Vol 357 (3) ◽  
pp. 719-728 ◽  
Author(s):  
Wen Bin WU ◽  
Shin C. CHANG ◽  
Ming-Yi LIAU ◽  
Tur-Fu HUANG
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Matrix Proteins ◽  
Dependent Manner ◽  
Single Chain ◽  
Human Endothelial Cells ◽  
Putative Precursor ◽  
Induced Apoptosis ◽  
Umbilical Vein Endothelial Cells ◽  
Dose Dependent

Apoptosis, a programmed, physiological mode of cell death, is important in tissue homoeostasis. Here we report that a new metalloproteinase, graminelysin I, purified from Trimeresurus gramineus venom, induced apoptosis of human endothelial cells as examined by electrophoresis and flow cytometry. Graminelysin I contains only a metalloproteinase domain. It is a single-chain proteinase with a molecular mass of 27020Da. cDNA sequence analysis revealed that the disintegrin-like and cysteine-rich domains of the putative precursor protein of graminelysin I are likely to be processed post-translationally, producing the proteinase domain (graminelysin I). Graminelysin I cleaved the α chain of fibrinogen preferentially and cleaved the β chain either on longer incubation or at higher concentration. Graminelysin I inhibited the adhesion of human umbilical-vein endothelial cells (HUVECs) to immobilized fibrinogen and induced HUVECs detachment in a dose-dependent manner. These effects on HUVECs were abolished when graminelysin I was pretreated with EDTA. However, graminelysin I did not inhibit the adhesion of HUVECs to immobilized collagen. HUVECs were susceptible to death after treatment with graminelysin I when they were cultured on immobilized fibrinogen. In contrast, HUVECs were rather resistant to treatment with graminelysin I if they were cultured on immobilized collagen. Furthermore, graminelysin I induced apoptosis of HUVECs in a dose-dependent manner. Similarly, its apoptosis-inducing activity was blocked if it was treated with EDTA. These results suggest that the catalytic activity of graminelysin I on matrix proteins contributes to its apoptosis-inducing activity.

scholarly journals Shear-dependent inhibition of granulocyte adhesion to cultured endothelium by dextran sulfate

Blood ◽  
1989 ◽  
Vol 73 (5) ◽  
pp. 1324-1330
Author(s):  
K Ley ◽  
E Lundgren ◽  
E Berger ◽  
KE Arfors
Keyword(s):  
Shear Stress ◽  
Dextran Sulfate ◽  
Leukocyte Adhesion ◽  
Umbilical Vein ◽  
Dependent Manner ◽  
Dependent Inhibition ◽  
Umbilical Vein Endothelial Cells ◽  
Dose Dependent ◽  
Adhesion Process

Adhesion of polymorphonuclear granulocytes (PMNs) in microvessels occurs in the presence of shear forces exerted by the blood flow. To model this in vitro, phorbol myristate acetate (PMA)-activated PMN were exposed to shear stress on cultured human umbilical vein endothelial cells (HUVECs) and on plastic dishes coated with bovine serum albumin (BSA). PMN adhesion to HUVECs averaged 36% of the total PMNs added and was reduced to 21% by shear stress of approximately 1.5 dynes.cm-2. On BSA, adhesion was reduced from 59% to 35%. Dextran sulfate (molecular weight 500,000) inhibited PMN adhesion in a dose-dependent manner when shear stress was applied. At a concentration of 1 mg.ml-1, inhibition was 72% on HUVECs and 76% on BSA. Half-maximal inhibition was reached at approximately 1 microgram.mL-1 dextran sulfate, corresponding to 2 nmol/L. Without shear stress, dextran sulfate had no effect on HUVECs and only a moderate effect on BSA. The murine monoclonal antibody (MoAb) 60.3, recognizing an epitope on the leukocyte adhesion glycoprotein CD18, inhibited PMN adhesion equally well with and without shear. A low dose of MoAb 60.3 enhanced the effect of dextran sulfate without shear stress. Flow cytometry (FACS) did not show inhibition of MoAb 60.3 binding to PMNs by dextran sulfate. These results indicate that a dextran sulfate-inhibitable adhesion process is important for PMN adhesion in the presence of shear stress.

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