Expression of CD34 in Pulmonary Endothelial Cells in vivo1

Pathobiology ◽  
2002 ◽  
Vol 70 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Annette M. Müller ◽  
Maya Nesslinger ◽  
Guido Skipka ◽  
Klaus-Michael Müller
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Endothelial Cells

Differential regulation of diverse physiological responses to VEGF in pulmonary endothelial cells

2001 ◽  
Vol 281 (6) ◽  
pp. L1500-L1511 ◽  
Author(s):  
Patrice M. Becker ◽  
Alexander D. Verin ◽  
Mary Ann Booth ◽  
Feng Liu ◽  
Anna Birukova ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Fetal Liver ◽  
Physiological Responses ◽  
Src Kinase ◽  
Endothelial Permeability ◽  
Barrier Dysfunction ◽  
Pulmonary Endothelial Cells ◽  
Mitogen Activated Protein ◽  
Lung Endothelial Cells

The mechanisms responsible for the divergent physiological responses of endothelial cells to vascular endothelial growth factor (VEGF) are incompletely understood. We hypothesized that VEGF elicits increased endothelial permeability and cell migration via differential activation of intracellular signal transduction pathways. To test this hypothesis, we established a model of VEGF-induced endothelial barrier dysfunction and chemotaxis with bovine pulmonary endothelial cells. We compared the effects of VEGF on transendothelial electrical resistance (TER), actin cytoskeletal remodeling, and chemotaxis of lung endothelial cells and then evaluated the role of the mitogen-activated protein kinases (MAPKs) p38 and extracellular signal-regulated kinase (ERK)1/2 in VEGF-mediated endothelial responses. The dose response of pulmonary arterial and lung microvascular endothelial cells to VEGF differed when barrier regulation and chemotaxis were evaluated. Inhibition of tyrosine kinase, phosphoinositol 3-kinase, or p38 MAPK significantly attenuated VEGF-mediated TER, F-actin remodeling, and chemotaxis. VEGF-mediated decreased TER was also significantly attenuated by inhibition of ERK1/2 MAPK but not by inhibition of fetal liver kinase-1 (flk-1) or Src kinase. In contrast, VEGF-mediated endothelial migration was not attenuated by ERK1/2 inhibition but was abolished by inhibition of either flk-1 or Src kinase. These data suggest potential mechanisms by which VEGF may differentially mediate physiological responses in vivo.

scholarly journals Mesenchymal stem cells-derived exosomal miRNA-28-3p promotes apoptosis of pulmonary endothelial cells in pulmonary embolism

2020 ◽  
Author(s):  
Hongyu Mao ◽  
Lina Liu ◽  
Yamin Hu
Keyword(s):  
Stem Cells ◽  
Pulmonary Embolism ◽  
Endothelial Cells ◽  
Mesenchymal Stem Cells ◽  
Luciferase Reporter ◽  
Apoptosis Resistance ◽  
Novel Therapy ◽  
Pulmonary Endothelial Cells

Abstract Background Pulmonary embolism (PE) is a primary clinical manifestation of venous thromboembolism (VTE). It has been demonstrated that pulmonary endothelial cells (PECs) are apoptotic-resistance in PE. In this study, PECs were collected from PE patients and mouse models. Western blot, RT-PCR, flow cytometry, H&E and TUNEL assay, confocal and TEM microscopy, and luciferase reporter assay were performed to determine the effects of miR-28-3p on PECs apoptosis and if exosomes can act as the shuttle to transport miR-28-3p to PECs. Material and Methods The results revealed that apoptosis and miR-28-3p were downregulated in PECs of PE. The miR-28-3p mimics and inhibitor enhanced and further inhibited apoptosis in PECs, respectively. Results Both miR-28-3p-modified adipose tissue-derived mesenchymal stem cells (AMSCs) and AMSC-derived exosomes upregulated miR-28-3p expression in PECs, leading to elevated apoptosis of PECs. Apoptosis inhibitor 5 (API5) was a direct target gene of miR-28-3p, and the overexpression of API5 in miR-28-3p-modified PECs further suppressed apoptosis. Conclusions Furthermore, the administration of miR-28-3p-modified exosomes to PE mouse model promoted apoptosis in PECs. In conclusion, exosomal miR-28-3p could ameliorate PE-associated apoptosis-resistance in PECs through targeting API5 in vitro and in vivo. Therefore, AMSCs-derived exosome is a promising way to deliver functioning miRNA to PECs, providing insight into novel therapy of PE.

scholarly journals Differential Innate Immune Responses Elicited by Nipah Virus and Cedar Virus Correlate with Disparate In Vivo Pathogenesis in Hamsters

Viruses ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 291 ◽  
Author(s):  
Tony Schountz ◽  
Corey Campbell ◽  
Kaitlyn Wagner ◽  
Joel Rovnak ◽  
Cynthia Martellaro ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Syrian Hamster ◽  
Nipah Virus ◽  
Neutralizing Antibody ◽  
Type I ◽  
Type I Ifn ◽  
Innate Immune Responses ◽  
Syrian Hamsters ◽  
Pulmonary Endothelial Cells

Syrian hamsters (Mesocricetus auratus) are a pathogenesis model for the Nipah virus (NiV), and we sought to determine if they are also susceptible to the Cedar virus (CedPV). Following intranasal inoculation with CedPV, virus replication occurred in the lungs and spleens of infected hamsters, a neutralizing antibody was produced in some hamsters within 8 days post-challenge, and no conspicuous signs of disease occurred. CedPV replicated to a similar magnitude as NiV-Bangladesh in type I IFN-deficient BHK-21 Syrian hamster fibroblasts but replicated 4 logs lower in type I IFN-competent primary Syrian hamster and human pulmonary endothelial cells, a principal target of henipaviruses. The coinfection of these cells with CedPV and NiV failed to rescue CedPV titers and did not diminish NiV titers, suggesting the replication machinery is virus-specific. Type I IFN response transcripts Ifna7, Ddx58, Stat1, Stat2, Ccl5, Cxcl10, Isg20, Irf7, and Iigp1 were all significantly elevated in CedPV-infected hamster endothelial cells, whereas Ifna7 and Iigp1 expression were significantly repressed during NiV infection. These results are consistent with the hypothesis that CedPV’s inability to counter the host type I IFN response may, in part, contribute to its lack of pathogenicity. Because NiV causes a fatal disease in Syrian hamsters with similarities to human disease, this model will provide valuable information about the pathogenic mechanisms of henipaviruses.

Expression of von Willebrand Factor by Human Pulmonary Endothelial Cells in vivo1

Respiration ◽  
2002 ◽  
Vol 69 (6) ◽  
pp. 526-533 ◽  
Author(s):  
Annette M. Müller ◽  
Carmen Skrzynski ◽  
Guido Skipka ◽  
Klaus-Michael Müller
Keyword(s):  
Endothelial Cells ◽  
Von Willebrand Factor ◽  
Pulmonary Endothelial Cells ◽  
Von Willebrand ◽  
Willebrand Factor

scholarly journals Angiotensin-Converting Enzyme 2 Inhibits Apoptosis of Pulmonary Endothelial Cells During Acute Lung Injury Through Suppressing MiR-4262

2015 ◽  
Vol 37 (2) ◽  
pp. 759-767 ◽  
Author(s):  
Hong Bao ◽  
Fengying Gao ◽  
Guogang Xie ◽  
Zhenwei Liu
Keyword(s):  
Endothelial Cells ◽  
Protein Translation ◽  
Mouse Lung ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Pulmonary Endothelial Cells ◽  
Pulmonary Cells ◽  
Induced Apoptosis

Background/Aims: Angiotensin converting enzyme 2 (ACE2) treatment suppresses the severity of acute lung injury (ALI). The effects of ACE2 in ALI have been shown to not only result from its antagonizing hydrolyzing angiotensin II (AngII), which is responsible for reduction in the vascular tension and pulmonary accumulation of inflammatory cells, but also result from a role of ACE2 in suppressing the ALI-induced apoptosis of pulmonary endothelial cells (PECs). Nevertheless, the underlying mechanisms of the role of ACE2 on PEC apoptosis are not completely understood. Methods: Here, we used a bleomycin-induced mouse model for ALI that has been published in our previous studies. We analyzed the mRNA and protein levels of an anti-apoptotic protein Bcl-2 in the ALI-mice that have been treated w/o ACE2. We analyzed miR-4262 levels in the mouse lung in these mice. Bcl-2-targeting miRNAs were predicted using bioinformatics algorithms and a luciferase reporter assay was applied to examine the effects of miR-4262 on the Bcl-2 protein translation upon their binding to 3'-UTR of Bcl-2 mRNA. Adeno-associated viruses carrying either miR-4262 mimics or antisense were injected into ALI-mice without ACE2, and their effects on the apoptosis in mouse lung cells were analyzed by Western blot. Results: ACE2 inhibited the ALI-induced apoptosis of pulmonary cells in vivo partially through upregulation of Bcl-2 protein, but not Bcl-2 mRNA. ACE2 appeared to significantly suppress the upregulation of miR-4262 in mouse lung after ALI. MiR-4262 was found to target 3'-UTR of Bcl-2 mRNA to inhibit its protein translation in PECs. In vivo administration of antisense of miR-4262 decreased apoptosis of pulmonary cells and severity of the ALI in mice. Conclusion: ACE2-induced suppression of miR-4262 partially contribute to the inhibition of the PEC apoptosis after ALI through Bcl-2. MiR-4262 may be a novel promising treatment target for ALI and ARDS.

Resveratrol Reduces Matrix Metalloproteinase-2 Activity Induced by Oxygen-Glucose Deprivation and Reoxygenation in Human Cerebral Microvascular Endothelial Cells

2012 ◽  
Vol 82 (4) ◽  
pp. 267-274 ◽  
Author(s):  
Zahide Cavdar ◽  
Mehtap Y. Egrilmez ◽  
Zekiye S. Altun ◽  
Nur Arslan ◽  
Nilgun Yener ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Neurovascular Unit ◽  
Glucose Deprivation ◽  
Matrix Metalloproteinase 2 ◽  
Microvascular Endothelial Cells ◽  
Oxygen Glucose Deprivation ◽  
Microvascular Endothelial

The main pathophysiology in cerebral ischemia is the structural alteration in the neurovascular unit, coinciding with neurovascular matrix degradation. Among the human matrix metalloproteinases (MMPs), MMP-2 and -9, known as gelatinases, are the key enzymes for degrading type IV collagen, which is the major component of the basal membrane that surrounds the cerebral blood vessel. In the present study, we investigated the effects of resveratrol on cytotoxicity, reactive oxygen species (ROS), and gelatinases (MMP-2 and -9) in human cerebral microvascular endothelial cells exposed to 6 hours of oxygen-glucose deprivation and a subsequent 24 hours of reoxygenation with glucose (OGD/R), to mimic ischemia/reperfusion in vivo. Lactate dehydrogenase increased significantly, in comparison to that in the normoxia group. ROS was markedly increased in the OGD/R group, compared to normoxia. Correspondingly, ROS was significantly reduced with 50 μM of resveratrol. The proMMP-2 activity in the OGD/R group showed a statistically significant increase from the control cells. Resveratrol preconditioning decreased significantly the proMMP-2 in the cells exposed to OGD/R in comparison to that in the OGD/R group. Our results indicate that resveratrol regulates MMP-2 activity induced by OGD/R via its antioxidant effect, implying a possible mechanism related to the neuroprotective effect of resveratrol.

An Electron Microscopic Study of Platelet Thrombus Formation in the Rabbit with Particular Regard to 5-Hydroxytryptamine Release

1967 ◽  
Vol 18 (03/04) ◽  
pp. 592-604 ◽  
Author(s):  
H. R Baumgartner ◽  
J. P Tranzer ◽  
A Studer
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Vessel Wall ◽  
Thrombus Formation ◽  
Endothelial Damage ◽  
Electron Microscopic ◽  
Rabbit Ear ◽  
Basement Lamina ◽  
Platelet Thrombus

SummaryElectron microscopic and histologic examination of rabbit ear vein segments 4 and 30 min after slight endothelial damage have yielded the following findings :1. Platelets do not adhere to damaged endothelial cells.2. If the vessel wall is denuded of the whole endothelial cell, platelets adhere to the intimai basement lamina as do endothelial cells.3. The distance between adherent platelets as well as endothelial cells and intimai basement lamina measures 10 to 20 mµ, whereas the distance between aggregated platelets is 30 to 60 mµ.4. 5-hydroxytryptamine (5-HT) is released from platelets during viscous metamorphosis at least in part as 5-HT organelles.It should be noted that the presence of collagen fibers is not necessary for platelet thrombus formation in vivo.

Desmopressin (DDAVP) Enhances Platelet Adhesion to the Extracellular Matrix of Cultured Human Endothelial Cells through Increased Expression of Tissue Factor

1997 ◽  
Vol 77 (05) ◽  
pp. 0975-0980 ◽  
Author(s):  
Angel Gálvez ◽  
Goretti Gómez-Ortiz ◽  
Maribel Díaz-Ricart ◽  
Ginés Escolar ◽  
Rogelio González-Sarmiento ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Tissue Factor ◽  
Platelet Adhesion ◽  
Umbilical Vein ◽  
Procoagulant Activity ◽  
Experimental Conditions ◽  
Chromogenic Assay

SummaryThe effect of desmopressin (DDAVP) on thrombogenicity, expression of tissue factor and procoagulant activity (PCA) of extracellular matrix (ECM) generated by human umbilical vein endothelial cells cultures (HUVEC), was studied under different experimental conditions. HUVEC were incubated with DDAVP (1, 5 and 30 ng/ml) and then detached from their ECM. The reactivity towards platelets of this ECM was tested in a perfusion system. Coverslips covered with DD A VP-treated ECMs were inserted in a parallel-plate chamber and exposed to normal blood anticoagulated with low molecular weight heparin (Fragmin®, 20 U/ml). Perfusions were run for 5 min at a shear rate of 800 s1. Deposition of platelets on ECMs was significantly increased with respect to control ECMs when DDAVP was used at 5 and 30 ng/ml (p <0.05 and p <0.01 respectively). The increase in platelet deposition was prevented by incubation of ECMs with an antibody against human tissue factor prior to perfusion. Immunofluorescence studies positively detected tissue factor antigen on DDAVP derived ECMs. A chromogenic assay performed under standardized conditions revealed a statistically significant increase in the procoagulant activity of the ECMs produced by ECs incubated with 30 ng/ml DDAVP (p <0.01 vs. control samples). Northern blot analysis revealed increased levels of tissue factor mRNA in extracts from ECs exposed to DDAVP. Our data indicate that DDAVP in vitro enhances platelet adhesion to the ECMs through increased expression of tissue factor. A similar increase in the expression of tissue factor might contribute to the in vivo hemostatic effect of DDAVP.

Epinephrine Induces von Willebrand Factor Release from Cultured Endothelial Cells: Involvement of Cyclic AMP-dependent Signalling in Exocytosis

1997 ◽  
Vol 77 (06) ◽  
pp. 1182-1188 ◽  
Author(s):  
Ulrich M Vischer ◽  
Claes B Wollheinn
Keyword(s):  
Endothelial Cells ◽  
Adenylate Cyclase ◽  
Von Willebrand Factor ◽  
Umbilical Vein ◽  
Free Calcium ◽  
Camp Content ◽  
Von Willebrand ◽  
Willebrand Factor

Summaryvon Willebrand factor (vWf) is released from endothelial cell storage granules after stimulation with thrombin, histamine and several other agents that induce an increase in cytosolic free calcium ([Ca2+]i). In vivo, epinephrine and the vasopressin analog DDAVP increase vWf plasma levels, although they are thought not to induce vWf release from endothelial cells in vitro. Since these agents act via a cAMP-dependent pathway in responsive cells, we examined the role of cAMP in vWf secretion from cultured human umbilical vein endothelial cells. vWf release increased by 50% in response to forskolin, which activates adenylate cyclase. The response to forskolin was much stronger when cAMP degradation was blocked with IBMX, an inhibitor of phosphodiesterases (+200%), whereas IBMX alone had no effect. vWf release could also be induced by the cAMP analogs dibutyryl-cAMP (+40%) and 8-bromo-cAMP (+25%); although their effect was weak, they clearly potentiated the response to thrombin. Epinephrine (together with IBMX) caused a small, dose-dependent increase in vWf release, maximal at 10-6 M (+50%), and also potentiated the response to thrombin. This effect is mediated by adenylate cyclase-coupled β-adrenergic receptors, since it is inhibited by propranolol and mimicked by isoproterenol. In contrast to thrombin, neither forskolin nor epinephrine caused an increase in [Ca2+]j as measured by fura-2 fluorescence. In addition, the effects of forskolin and thrombin were additive, suggesting that they act through distinct signaling pathways. We found a close correlation between cellular cAMP content and vWf release after stimulation with epinephrine and forskolin. These results demonstrate that cAMP-dependent signaling events are involved in the control of exocytosis from endothelial cells (an effect not mediated by an increase in [Ca2+]i) and provide an explanation for epinephrine-induced vWf release.

Sign in / Sign up

Export Citation Format

Share Document