ETA receptors are present in human aortic vascular endothelial cells and modulate intracellular calciumThis article is one of a selection of papers published in the two-part special issue entitled 20 Years of Endothelin Research.

2010 ◽  
Vol 88 (8) ◽  
pp. 817-829 ◽  
Author(s):  
Levon Avedanian ◽  
Julie Riopel ◽  
Ghassan Bkaily ◽  
Moni Nader ◽  
Pedro D’Orleans-Juste ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Receptor Antagonist ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Blot Technique ◽  
Intracellular Ca ◽  
Envelope Membranes ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Selection Of

Using immunofluorescence and real 3-D confocal microscopy, our results showed the presence of ET-1, ETA, and ETB receptors in isolated human aortic vascular endothelial cells (hVECs). The level of the peptide and its receptors was significantly higher in the nucleus (including the nuclear envelope membranes) than in the cytosol (including the cell membrane). Furthermore, using the Western blot technique we demonstrated the presence of both ETA and ETB receptors. Using intact and isolated human hVECs and the Fura-2 calcium (Ca2+) measurement technique, we showed that ET-1 induced a dose-dependent increase of total intracellular free Ca2+, with an EC50 of 1.3 × 10−10 mol/L. The specific ETA receptor antagonist ABT-627 (10−7 mol/L), but not the ETB receptor antagonist A-192621 (10−7 mol/L), prevented the ET-1 (10−9 mol/L) induced increase of total intracellular Ca2+. In conclusion, these results clearly show that similar to ETB receptors, ETA receptors are also present in human aortic vascular endothelial cells and their levels are higher than ETB in the nucleus when compared with the cytosol. Furthermore, we suggest that ETA, but not ETB, receptors mediate the effect of ET-1 on total intracellular Ca2+ of human aortic vascular endothelial cells.

scholarly journals Depletion of the inositol 1,4,5-trisphosphate-sensitive intracellular Ca2+ store in vascular endothelial cells activates the agonist-sensitive Ca2+-influx pathway

1992 ◽  
Vol 284 (2) ◽  
pp. 521-530 ◽  
Author(s):  
W P Schilling ◽  
O A Cabello ◽  
L Rajan
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Cyclopiazonic Acid ◽  
Phosphoinositide Hydrolysis ◽  
Vascular Endothelial ◽  
The Novel ◽  
Excitable Cells ◽  
Atpase Inhibitors ◽  
Dose Dependent Increase ◽  
Dose Dependent

Previous studies in non-excitable cells have suggested that depletion of internal Ca2+ stores activates Ca2+ influx from the extracellular space via a mechanism that does not require stimulation of phosphoinositide hydrolysis. To test this hypothesis in vascular endothelial cells, the effect of the Ca(2+)-ATPase/pump inhibitor 2,5-di-t-butylhydroquinone (BHQ) on cytosolic free Ca2+ concentration ([Ca2+]i) was examined. BHQ produced a dose-dependent increase in [Ca2+]i, which remained elevated over basal values for several minutes and was substantially inhibited in the absence of extracellular Ca2+. Application of bradykinin after BHQ demonstrated that the BHQ-sensitive compartment partially overlapped the bradykinin-sensitive store. Similar results were obtained with thapsigargin and cyclopiazonic acid, two other Ca(2+)-ATPase inhibitors. Although BHQ had no effect on phosphoinositide hydrolysis, both 45Ca2+ influx and efflux were stimulated by this agent. These results suggest that depletion of the agonist-sensitive Ca2+ store is sufficient for activation of Ca2+ influx. Several characteristics of the Ca(2+)-influx pathway activated by internal store depletion were compared with those of the agonist-activated pathway. Bradykinin-stimulated Ca2+ influx was increased at alkaline extracellular pH (pHo), and was inhibited by extracellular La3+, by depolarization of the membrane, and by the novel Ca(2+)-influx blocker 1-(beta-[3-(4-methoxyphenyl)propoxy]-4- methoxyphenethyl)-1H-imidazole hydrochloride (SKF 96365). Additionally, bradykinin stimulated influx of both 45Ca2+ and 133Ba2+, consistent with the hypothesis that the agonist-activated influx pathway is permeable to both of these bivalent cations. Likewise, activation of Ca2+ influx by BHQ, thapsigargin and cyclopiazonic acid was blocked by La3+, membrane depolarization and SKF 96365, but was unaffected by nitrendipine or BAY K 8644. Furthermore, Ca2+ influx stimulated by BHQ was increased at alkaline pHo and BHQ stimulated the influx of both 45Ca2+ and 133Ba2+ to the same extent. These results demonstrate that the agonist-activated Ca(2+)-influx pathway and the pathway activated by depletion of the agonist-sensitive internal Ca2+ store are indistinguishable.

scholarly journals Citrus bergamiaRisso Elevates Intracellular Ca2+in Human Vascular Endothelial Cells due to Release of Ca2+from Primary Intracellular Stores

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Purum Kang ◽  
Seung Ho Han ◽  
Hea Kyung Moon ◽  
Jeong-Min Lee ◽  
Hyo-Keun Kim ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Channel Blocker ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Concentration Dependent Manner ◽  
Carbonyl Cyanide ◽  
Intracellular Ca ◽  
Umbilical Vein Endothelial Cells

The purpose of the present study is to examine the effects of essential oil ofCitrus bergamiaRisso (bergamot, BEO) on intracellular Ca2+in human umbilical vein endothelial cells. Fura-2 fluorescence was used to examine changes in intracellular Ca2+concentration[Ca2+]i. In the presence of extracellular Ca2+, BEO increased[Ca2+]i, which was partially inhibited by a nonselective Ca2+channel blocker La3+. In Ca2+-free extracellular solutions, BEO increased[Ca2+]iin a concentration-dependent manner, suggesting that BEO mobilizes intracellular Ca2+. BEO-induced[Ca2+]iincrease was partially inhibited by a Ca2+-induced Ca2+release inhibitor dantrolene, a phospholipase C inhibitor U73122, and an inositol 1,4,5-triphosphate (IP3)-gated Ca2+channel blocker, 2-aminoethoxydiphenyl borane (2-APB). BEO also increased[Ca2+]iin the presence of carbonyl cyanide m-chlorophenylhydrazone, an inhibitor of mitochondrial Ca2+uptake. In addition, store-operated Ca2+entry (SOC) was potentiated by BEO. These results suggest that BEO mobilizes Ca2+from primary intracellular stores via Ca2+-induced and IP3-mediated Ca2+release and affect promotion of Ca2+influx, likely via an SOC mechanism.

scholarly journals GAS6 Inhibits Granulocyte Adhesion to Endothelial Cells

Blood ◽  
1998 ◽  
Vol 91 (7) ◽  
pp. 2334-2340
Author(s):  
Gian Carlo Avanzi ◽  
Margherita Gallicchio ◽  
Flavia Bottarel ◽  
Loretta Gammaitoni ◽  
Giuliana Cavalloni ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Platelet Activating Factor ◽  
Polymorphonuclear Cells ◽  
Vascular Endothelial ◽  
Tnf Α ◽  
High Concentrations ◽  
Adhesive Interactions ◽  
Factor Α ◽  
Dose Dependent

GAS6 is a ligand for the tyrosine kinase receptors Rse, Axl, and Mer, but its function is poorly understood. Previous studies reported that both GAS6 and Axl are expressed by vascular endothelial cells (EC), which play a key role in leukocyte extravasation into tissues during inflammation through adhesive interactions with these cells. The aim of this work was to evaluate the GAS6 effect on the adhesive function of EC. Treatment of EC with GAS6 significantly inhibited adhesion of polymorphonuclear cells (PMN) induced by phorbol 12-myristate 13-acetate (PMA), platelet-activating factor (PAF), thrombin, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), but not that induced by FMLP and IL-8. GAS6 did not affect adhesion to resting EC. Titration experiments showed that high concentrations of GAS6 were needed to inhibit PMN adhesion and that inhibition was dose-dependent at the concentration range of 0.1 to 1 μg/mL. One possibility was that high concentrations were needed to overwhelm the effect of endogenous GAS6 produced by EC. In line with this possibility, treatment of resting EC with soluble Axl significantly potentiated PMN adhesion. Analysis of localization of GAS6 by confocal microscopy and cytofluorimetric analysis showed that it is concentrated along the plasma membrane in resting EC and treatment with PAF induces depletion and/or redistribution of the molecule. These data suggest that GAS6 functions as a physiologic antiinflammatory agent produced by resting EC and depleted when proinflammatory stimuli turn on the proadhesive machinery of EC.

Function of Tissue-type Plasminogen Activator Releaser on Vascular Endothelial Cells and Thrombolysis In Vivo

2002 ◽  
Vol 87 (06) ◽  
pp. 1069-1074 ◽  
Author(s):  
Hiroyuki Matsuno ◽  
Mikio Hayashi ◽  
Koji Horibuchi ◽  
Kiyotaka Okada ◽  
Hideharu Fukao ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Tissue Type ◽  
Vascular Endothelial ◽  
Thrombosis Model ◽  
Artery Thrombosis ◽  
Type Plasminogen Activator ◽  
Thrombolytic Effect ◽  
Dose Dependent

SummaryThe effect of monosodium[2-(6-hydroxynaphthalen-2-yl)-6-methylpyrimidin-4-yloxy]acetate dihydrate (JTV-926) on fibrinolysis was investigated in vitro and in vivo. JTV-926 released tissue-type plasminogen activator (t-PA) from human vascular endothelial cells in a dose-dependent manner. The thrombolytic effect of JTV-926 was studied using three animal thrombosis models; a photo-irradiation-induced mouse carotid artery thrombosis model, a photo-irradiation-induced rat femoral artery thrombosis model and a thrombin-induced rat venous thrombosis model. In the mouse thrombosis model, t-PA deficient mice (t-PA−/−mice) and their wild-type (t-PA+/+) were used. JTV-926 was injected as a bolus 30 min after the interruption of blood flow by an occlusion thrombi. Blood flow was continuously monitored for 180 min after intravenous administration of JTV-926 (1 mg/kg). Although the recanalization rate of the occluded artery was 37.5% in t-PA +/+ mice with the vehicle control, it increased to 75% in t-PA+/+ mice after JTV-926 administration. However, when JTV-926 was administrated in t-PA−/−mice, vascular recanalization was not observed in any arteries. In the photo-irradiation-induced rat femoral artery thrombosis model, intra-duodenal administration of JTV-926 induced thrombolysis. Moreover, in the thrombin-induced rat venous thrombosis model, the dose-dependent thrombolysis was also observed by oral administration of JTV-926. It was suggested that JTV-926 revealed a sufficient thrombolytic effect through the absorption from the intestine. Thus, a newly synthesized compound, JTV-926 induced t-PA release from vascular endothelial cells and effective thrombolysis in vivo.

scholarly journals Dehydroepiandrosterone Protects Vascular Endothelial Cells against Apoptosis through a Gαi Protein-Dependent Activation of Phosphatidylinositol 3-Kinase/Akt and Regulation of Antiapoptotic Bcl-2 Expression

Endocrinology ◽  
2007 ◽  
Vol 148 (7) ◽  
pp. 3068-3076 ◽  
Author(s):  
Dongmin Liu ◽  
Hongwei Si ◽  
Kathryn A. Reynolds ◽  
Wei Zhen ◽  
Zhenquan Jia ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Estrogen Receptor ◽  
Vascular Function ◽  
Vascular Endothelial Cells ◽  
Specific Inhibitor ◽  
Vascular Endothelial ◽  
Phosphatidylinositol 3 Kinase ◽  
Antiapoptotic Effect ◽  
Dose Dependent ◽  
Phosphatidylinositol 3

The adrenal steroid dehydroepiandrosterone (DHEA) may improve vascular function, but the mechanism is unclear. In the present study, we show that DHEA significantly increased cell viability, reduced caspase-3 activity, and protected both bovine and human vascular endothelial cells against serum deprivation-induced apoptosis. This effect was dose dependent and maximal at physiological concentrations (0.1–10 nm). DHEA stimulation of bovine aortic endothelial cells resulted in rapid and dose-dependent phosphorylation of Akt, which was blocked by LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K), the upstream kinase of Akt. Accordingly, inhibition of PI3K or transfection of the cells with dominant-negative Akt ablated the antiapoptotic effect of DHEA. The induced Akt phosphorylation and subsequent cytoprotective effect of DHEA were dependent on activation of Gαi proteins, but were estrogen receptor independent, because these effects were blocked by pertussis toxin but not by the estrogen receptor inhibitor ICI182,780 or the aromatase inhibitor aminoglutethimide. Finally, DHEA enhanced antiapoptotic Bcl-2 protein expression, its promoter activity, and gene transcription attributable to the activation of the PI3K/Akt pathway. Neutralization of Bcl-2 by antibody transfection significantly decreased the antiapoptotic effect of DHEA. These findings provide the first evidence that DHEA acts as a survival factor for endothelial cells by triggering the Gαi-PI3K/Akt-Bcl-2 pathway to protect cells against apoptosis. This may represent an important mechanism underlying the vascular protective effect of DHEA.

scholarly journals Inhibition of vascular endothelial cell prostacyclin synthesis by plasmin

Blood ◽  
1989 ◽  
Vol 74 (3) ◽  
pp. 1015-1020 ◽  
Author(s):  
AI Schafer ◽  
R Rodriguez ◽  
J Loscalzo ◽  
MA Jr Gimbrone
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial Cell ◽  
Fibrinolytic System ◽  
Pharmacologic Therapy ◽  
Ionophore A23187 ◽  
Vascular Endothelial ◽  
Plasmin Activity ◽  
Dependent Inhibition ◽  
Dose Dependent

Vascular endothelial cells (EC) play an active role in the synthesis and assembly of components of the fibrinolytic system and the generation of the major fibrinolytic protease plasmin. However, the reciprocal effects of plasmin on EC function have not been previously examined. We have studied the actions of plasmin on the production of prostacyclin (PGI2) by cultured human umbilical vein (HUVEC) and bovine aortic (BAEC) endothelial cells. Plasmin causes little or no direct stimulation of PGI2 formation by EC. Preincubation of EC with plasmin, however, produces a time- and concentration-dependent inhibition of ionophore A23187-, thrombin-, and histamine-induced PGI2 synthesis; a smaller inhibitory effect on arachidonate- and PGH2-induced PGI2 synthesis is found. Incubation of HUVEC or BAEC with a physiologic concentration of plasminogen (180 micrograms/mL) and recombinant tissue plasminogen activator (tPA) generates tPA dose-dependent plasmin activity that exceeds that generated in the absence of EC. In the presence of plasminogen, tPA also causes a tPA dose-dependent inhibition of thrombin- and ionophore A23187-stimulated PGI2 production. PGI2 inhibitory plasmin activity is generated within the concentration range of tPA achieved in plasma during pharmacologic therapy with tPA. These findings suggest that vascular endothelial cells not only regulate activation of the fibrinolytic system but may also be targets of plasmin action on PGI2 synthesis in the modulation of hemostasis and thrombosis.

scholarly journals The Study on Angiotensin II Induced-Ferroptosis in Vascular Endothelial Cells

2021 ◽  
Author(s):  
hong fang ◽  
Chi liu ◽  
Omer Cavdar ◽  
Yi Shen
Keyword(s):  
Endothelial Cells ◽  
Angiotensin Ii ◽  
Molecular Marker ◽  
Analysis Of Variance ◽  
Vascular Endothelial Cells ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Ang Ii ◽  
Valsartan Group ◽  
Dose Dependent

Abstract PurposeTo verify the effect of Angiotensin II on ferroptosis in vascular endothelial cells and clarify the related mechanism. MethodsHUVECs were evaluated for p53, P21,ALOX12, VEGF, MDA,GSH. Molecular marker impact upon AngII-induced ferroptosis was evaluated with students’ t-test，one-way analysis of variance (ANOVA).ResultsAs the concentration of Ang II increased，the level of ALOX12, P53,GSH and MDA increased in HUVECs. The expression of VEGFA in HUVECs is negatively correlated with dose of Ang II. Incubation of HUVECs in AngII and valsartan for 48hr reduces ALOX12, P21, GSH and MDA. Compared with the single AngII group, ALOX12, P21, GSH and MDA in valsartan group was decreased significantly（p=0.000）.In pifithrin-α hydrobromide-treated, ALOX12, P21, GSH and MDA was reduced significantly, as compared to valsartan group（p=0.000）. The most larger reduction in ALOX12, P21,GSH and MDA was pifithrin - α hydrobromide combined with valsartan group. In contrast, the expression of VEGFA increased significantly after HUVECs were treated with pifithrin - α hydrobromide and valsartan（p=0.000）.ConclusionsAngII can induce ferroptosis of vascular endothelial cells in a dose-dependent manner. The mechanism of AngII-induced ferroptosis may be regulated through the signal axis of ATR1,2-p53-ALOX12.

17 beta-Oestradiol inhibits stimulated endothelin release in human vascular endothelial cells

1997 ◽  
pp. 205-208 ◽  
Author(s):  
CS Wingrove ◽  
JC Stevenson
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Vascular Health ◽  
Human Endothelial Cells ◽  
Protective Properties ◽  
The Media ◽  
Potent Vasoconstrictor ◽  
Oxide Synthase ◽  
Dose Dependent

Oestrogen is believed to possess cardiovascular protective properties. Endothelin-1 (ET-1) is a potent vasoconstrictor and mitogen for vascular smooth muscle cells. We have investigated release of ET-1 from human endothelial cells in response to 17 beta-oestradiol. Serum was found to stimulate significantly ET-1 release during the first 4 h of culture. 17 beta-Oestradiol significantly reduced ET-1 immunoreactivity in the media of treated cells by up to 49% of control values after 4 h. This effect was found to be inversely related to the dose of 17 beta-oestradiol. Significant dose-dependent increases in nitric oxide synthase expression were observed in response to oestrogen after 24 h but not after 4 h. Serum-free experiments demonstrated that low doses of oestrogen were able to inhibit thrombin-induced ET-1 release whilst supraphysiological levels did not. These results provide a further perspective on the ability of oestrogens to maintain vascular health.

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