Inhibition of vascular endothelial cell prostacyclin synthesis by plasmin

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.

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Inhibition of vascular endothelial cell prostacyclin synthesis by plasmin

Blood ◽

10.1182/blood.v74.3.1015.1015 ◽

1989 ◽

Vol 74 (3) ◽

pp. 1015-1020 ◽

Cited By ~ 1

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

Abstract 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.

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Alterations in Vascular Endothelial Cell-related Plasma Proteins In Thalassaemic Patients and their Correlation with Clinical Symptoms

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649879 ◽

1995 ◽

Vol 74 (04) ◽

pp. 1045-1049 ◽

Cited By ~ 38

Author(s):

P Butthep ◽

A Bunyaratvej ◽

Y Funahara ◽

H Kitaguchi ◽

S Fucharoen ◽

...

Keyword(s):

Endothelial Cells ◽

Endothelial Cell ◽

Immunosorbent Assay ◽

Plasma Proteins ◽

Clinical Symptoms ◽

Vascular Endothelial Cells ◽

Vascular Endothelial Cell ◽

Enzyme Linked Immunosorbent Assay ◽

Vascular Endothelial ◽

Leg Ulcers

SummaryAn increased level of plasma thrombomodulin (TM) in α- and β- thalassaemia was demonstrated using an enzyme-linked immunosorbent assay (ELISA). Nonsplenectomized patients with β-thalassaemia/ haemoglobin E (BE) had higher levels of TM than splenectomized cases (BE-S). Patients with leg ulcers (BE-LU) were found to have the highest increase in TM level. Appearance of larger platelets in all types of thalassaemic blood was observed indicating an increase in the number of younger platelets. These data indicate that injury of vascular endothelial cells is present in thalassaemic patients.

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GAS6 Inhibits Granulocyte Adhesion to Endothelial Cells

Blood ◽

10.1182/blood.v91.7.2334.2334_2334_2340 ◽

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.

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Salmonella Typhimurium L Forms Induce Vascular Endothelial Cell Apoptosis via Mitochondrial-dependent Pathway

10.21203/rs.3.rs-109267/v2 ◽

2021 ◽

Author(s):

Jinhai Zhai ◽

Cuiping Yang ◽

Tao Zhang ◽

Dengyu Chen

Keyword(s):

Endothelial Cells ◽

Salmonella Typhimurium ◽

Cell Apoptosis ◽

Vascular Endothelial Cells ◽

Vascular Endothelial Cell ◽

Intestinal Lumen ◽

Vascular Endothelial ◽

Caspase 9 ◽

Apoptosis Pathway ◽

Significant Difference

Abstract BackgroundSalmonella typhimurium is a pathogenic gram-negative bacterium, which is found primarily in the intestinal lumen. It often causes diarrhea in infants and young children and leads to food poisoning, as well as septicemia and septic shock. In this study, we investigated the phenomenon and mechanism of vascular endothelial cells apoptosis induced by Salmonella typhimurium L forms, in order to recognize and control Salmonella typhimurium L-form infection.Methods The apoptosis of vascular endothelial cells at 8 hours after infection with Salmonella typhimurium L forms was determined by flow cytometric assay and fluoroscopy of Annexin V-FITC/PI staining. Caspase-9 was detected by spectrophotometer. Results Salmonella typhimurium L forms can induce apoptosis of vascular endothelial cells, with significant difference in the apoptosis rate compared with the control. Caspase-9 expression is higher than that of the control. Conclusion The ability to induce cell apoptosis of vascular endothelial cells by Salmonella typhimurium L forms may be related to mitochondria apoptosis pathway depending on Caspase-9.

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Immobilized DNA aptamers used as potent attractors for vascular endothelial cell: in vitro study of female rat

Bioscience Reports ◽

10.1042/bsr20182444 ◽

2020 ◽

Vol 40 (1) ◽

Cited By ~ 1

Author(s):

Jung-Joon Cha ◽

Hoyeon Lee ◽

Miyoung Kim ◽

Juyoung Kang ◽

Hanlim Song ◽

...

Keyword(s):

Endothelial Cells ◽

Vascular Function ◽

Therapeutic Potential ◽

Vascular Endothelial Cells ◽

Specific Binding ◽

Vascular Endothelial Cell ◽

Dna Aptamers ◽

Female Rat ◽

Vascular Endothelial

Abstract Vascular endothelial cells are essential to vascular function and maintenance. Dysfunction of these cells can lead to the development of cardiovascular disease or contribute to tumorigenesis. As such, the therapeutic modulation and monitoring of vascular endothelial cells are of significant clinical interest, and several endothelial-specific ligands have been developed for drug delivery and the monitoring of endothelial function. However, the application of these ligands has been limited by their high cost and tendency to induce immune responses, highlighting a need for alternate methods of targeting vascular endothelial cells. In the present study, we explore the therapeutic potential of DNA aptamers. Using cell-SELEX technology, we identified two aptamers with specific binding affinity for vascular endothelial cells and propose that these molecules show potential for use as new ligands for drug and biomarker research concerning vascular endothelial cells.

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

Thrombosis and Haemostasis ◽

10.1055/s-0037-1613134 ◽

2002 ◽

Vol 87 (06) ◽

pp. 1069-1074 ◽

Cited By ~ 7

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.

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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 ◽

10.1210/en.2006-1378 ◽

2007 ◽

Vol 148 (7) ◽

pp. 3068-3076 ◽

Cited By ~ 74

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.

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CYLD regulates angiogenesis by mediating vascular endothelial cell migration

Blood ◽

10.1182/blood-2009-10-248526 ◽

2010 ◽

Vol 115 (20) ◽

pp. 4130-4137 ◽

Cited By ~ 52

Author(s):

Jinmin Gao ◽

Lei Sun ◽

Lihong Huo ◽

Min Liu ◽

Dengwen Li ◽

...

Keyword(s):

Endothelial Cells ◽

Cell Migration ◽

Endothelial Cell ◽

Vascular Endothelial Cells ◽

Vascular Endothelial Cell ◽

Tube Formation ◽

Endothelial Cell Migration ◽

Vascular Endothelial

Cylindromatosis (CYLD) is a deubiquitinase that was initially identified as a tumor suppressor and has recently been implicated in diverse normal physiologic processes. In this study, we have investigated the involvement of CYLD in angiogenesis, the formation of new blood vessels from preexisting ones. We find that knockdown of CYLD expression significantly impairs angiogenesis in vitro in both matrigel-based tube formation assay and collagen-based 3-dimensional capillary sprouting assay. Disruption of CYLD also remarkably inhibits angiogenic response in vivo, as evidenced by diminished blood vessel growth into the angioreactors implanted in mice. Mechanistic studies show that CYLD regulates angiogenesis by mediating the spreading and migration of vascular endothelial cells. Silencing of CYLD dramatically decreases microtubule dynamics in endothelial cells and inhibits endothelial cell migration by blocking the polarization process. Furthermore, we identify Rac1 activation as an important factor contributing to the action of CYLD in regulating endothelial cell migration and angiogenesis. Our findings thus uncover a previously unrecognized role for CYLD in the angiogenic process and provide a novel mechanism for Rac1 activation during endothelial cell migration and angiogenesis.

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Endothelial HIF signaling regulates pulmonary fibrosis-associated pulmonary hypertension

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00258.2015 ◽

2016 ◽

Vol 310 (3) ◽

pp. L249-L262 ◽

Cited By ~ 42

Author(s):

Andrew J. Bryant ◽

Ryan P. Carrick ◽

Melinda E. McConaha ◽

Brittany R. Jones ◽

Sheila D. Shay ◽

...

Keyword(s):

Endothelial Cells ◽

Pulmonary Hypertension ◽

Endothelial Cell ◽

Pulmonary Fibrosis ◽

Vascular Endothelial Cells ◽

Vascular Endothelial Cell ◽

Tissue Growth ◽

Vascular Endothelial ◽

Pulmonary Vessel ◽

Deficient Mice

Pulmonary hypertension (PH) complicating chronic parenchymal lung disease, such as idiopathic pulmonary fibrosis, results in significant morbidity and mortality. Since the hypoxia-inducible factor (HIF) signaling pathway is important for development of pulmonary hypertension in chronic hypoxia, we investigated whether HIF signaling in vascular endothelium regulates development of PH related to pulmonary fibrosis. We generated a transgenic model in which HIF is deleted within vascular endothelial cells and then exposed these mice to chronic intraperitoneal bleomycin to induce PH associated with lung fibrosis. Although no differences in the degree of fibrotic remodeling were observed, we found that endothelial HIF-deficient mice were protected against development of PH, including right ventricle and pulmonary vessel remodeling. Similarly, endothelial HIF-deficient mice were protected from PH after a 4-wk exposure to normobaric hypoxia. In vitro studies of pulmonary vascular endothelial cells isolated from the HIF-targeted mice and controls revealed that endothelial HIF signaling increases endothelial cell expression of connective tissue growth factor, enhances vascular permeability, and promotes pulmonary artery smooth muscle cell proliferation and wound healing ability, all of which have the potential to impact the development of PH in vivo. Taken together, these studies demonstrate that vascular endothelial cell HIF signaling is necessary for development of hypoxia and pulmonary fibrosis associated PH. As such, HIF and HIF-regulated targets represent a therapeutic target in these conditions.

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

10.21203/rs.3.rs-565583/v1 ◽

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.

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