scholarly journals Inhibition of Elastin Peptide-Mediated Angiogenic Signaling Mechanism(s) in Choroidal Endothelial Cells by the α6(IV)NC1 Collagen Fragment

2013 ◽  
Vol 54 (13) ◽  
pp. 7828 ◽  
Author(s):  
Venugopal Gunda ◽  
Raj Kumar Verma ◽  
Yakkanti Akul Sudhakar
Keyword(s):  
Endothelial Cells ◽  
Signaling Mechanism ◽  
Collagen Fragment

Mechanotransduction by integrin is essential for IL-6 secretion from endothelial cells in response to uniaxial continuous stretch

2005 ◽  
Vol 288 (5) ◽  
pp. C1012-C1022 ◽  
Author(s):  
Akitoshi Sasamoto ◽  
Masato Nagino ◽  
Satoshi Kobayashi ◽  
Keiji Naruse ◽  
Yuji Nimura ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Kinase Inhibitor ◽  
Umbilical Vein ◽  
Nuclear Factor Κb ◽  
Inhibitory Peptide ◽  
Signaling Mechanism ◽  
Iκb Kinase ◽  
Intracellular Ca ◽  
Protein Kinase C Inhibitor ◽  
Umbilical Vein Endothelial Cells

We previously reported that uniaxial continuous stretch in human umbilical vein endothelial cells (HUVECs) induced interleukin-6 (IL-6) secretion via IκB kinase (IKK)/nuclear factor-κB (NF-κB) activation. The aim of the present study was to clarify the upstream signaling mechanism responsible for this phenomenon. Stretch-induced IKK activation and IL-6 secretion were inhibited by application of α5β1 integrin-inhibitory peptide (GRGDNP), phosphatidylinositol 3-kinase inhibitor (LY-294002), phospholipase C-γ inhibitor (U-73122), or protein kinase C inhibitor (H7). Although depletion of intra- or extracellular Ca2 + pool using thapsigargin (TG) or EGTA, respectively, showed little effect, a TG-EGTA mixture significantly inhibited stretch-induced IKK activation and IL-6 secretion. An increase in the intracellular Ca2 + concentration ([Ca2 +]i) upon continuous stretch was observed even in the presence of TG, EGTA, or GRGDNP, but not in a solution containing the TG-EGTA mixture, indicating that both integrin activation and [Ca2 +]i rise are crucial factors for stretch-induced IKK activation and after IL-6 secretion in HUVECs. Furthermore, while PKC activity was inhibited by the TG-EGTA mixture, GRGDNP, LY-294002, or U-73122, PLC-γ activity was retarded by GRGDNP or LY-294002. These results indicate that continuous stretch-induced IL-6 secretion in HUVECs depends on outside-in signaling via integrins followed by a PI3-K-PLC-γ-PKC-IKK-NF-κB signaling cascade. Another crucial factor, [Ca2 +]i increase, may at least be required to activate PKC needed for NF-κB activation.

Abstract P122: Mitochondrial Transcription Factor 2B Regulates Endothelial Cell Morphology

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Steven J Forrester ◽  
Tatsuo Kawai ◽  
Katherine J Elliot ◽  
Kunie Eguchi ◽  
Joon Y Park ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Transcription Factor ◽  
Cardiovascular Diseases ◽  
Cell Morphology ◽  
Mitochondrial Function ◽  
Umbilical Vein ◽  
Fold Increase ◽  
Mitochondrial Transcription ◽  
Signaling Mechanism ◽  
Mitochondrial Transcription Factor

Mitochondrial dysfunction, such as observed in endothelial cells, has been implicated in various cardiovascular diseases including, hypertension and atherosclerosis. Mitochondrial transcription factor 2B (TFB2M) is an essential component to maintain proper transcriptional and functional control of mitochondrial DNA. As well, elongation of endothelial cells is a characteristic of atheroprotective regions within the vasculature, and the relationship between the mitochondria and EC shape is currently unknown. The aim of our study is to investigate the hypothesis that TFB2M has a novel role in enhancing endothelial function. Human umbilical vein endothelial cells (HUVECs) were harvested 72 hours after adenoviral transduction with TFB2M (100 moi). HUVECs transduced with TFB2M showed an elongated cell morphology when compared to GFP control. To further investigate the effect of TFB2M on regulating mitochondrial function and cell shape, immunoblotting was carried out for markers involved in mitochondrial function/dynamics and markers indicative of cytoskeleton reorganization. TFB2M transduction resulted in increased expression of mitochondrial biogenesis marker VDAC (2.6 fold increase), mitochondrial fusion protein MFN2 (2.1 fold increase), and phosphorylated myosin phosphatase targeting protein MYPT1 at Thr850 (2.2 fold increase, p < 0.05 for all proteins). Additionally, fluorescence microscopy showed enhanced mitochondrial fluorescence in TFB2M transduced cells using mitotracker red staining (3.5 fold increase, p < 0.001). These data indicate that TFB2M has a previously undiscovered function contributing to altered EC function and shape, potentially through a novel mitochondrial retrograde signaling mechanism. Further research will focus on distinguishing the exact mechanisms culminating in a protective EC phenotype and the beneficial role of endothelial TFB2M-mediated enhanced mitochondrial function in the treatment of EC dysfunction associated with various cardiovascular diseases.

NAADP links histamine H1 receptors to secretion of von Willebrand factor in human endothelial cells

Blood ◽  
2011 ◽  
Vol 117 (18) ◽  
pp. 4968-4977 ◽  
Author(s):  
Bianca Esposito ◽  
Guido Gambara ◽  
Alexander M. Lewis ◽  
Fioretta Palombi ◽  
Alessio D'Alessio ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endoplasmic Reticulum ◽  
Von Willebrand Factor ◽  
Calcium Release ◽  
Umbilical Vein ◽  
Pore Channel ◽  
Human Endothelial Cells ◽  
Signaling Mechanism ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract A variety of endothelial agonist–induced responses are mediated by rises in intracellular Ca2+, suggesting that different Ca2+ signatures could fine-tune specific inflammatory and thrombotic activities. In search of new intracellular mechanisms modulating endothelial effector functions, we identified nicotinic acid adenine dinucleotide phosphate (NAADP) as a crucial second messenger in histamine-induced Ca2+ release via H1 receptors (H1R). NAADP is a potent intracellular messenger mobilizing Ca2+ from lysosome-like acidic compartments, functionally coupled to the endoplasmic reticulum. Using the human EA.hy926 endothelial cell line and primary human umbilical vein endothelial cells, we show that selective H1R activation increases intracellular NAADP levels and that H1R-induced calcium release involves both acidic organelles and the endoplasmic reticulum. To assess that NAADP links H1R to Ca2+-signaling we used both microinjection of self-inactivating concentrations of NAADP and the specific NAADP receptor antagonist, Ned-19, both of which completely abolished H1R-induced but not thrombin-induced Ca2+ mobilization. Interestingly, H1R-mediated von Willebrand factor (VWF) secretion was completely inhibited by treatment with Ned-19 and by siRNA knockdown of 2-pore channel NAADP receptors, whereas thrombin-induced VWF secretion failed to be affected. These findings demonstrate a novel and specific Ca2+-signaling mechanism activated through H1R in human endothelial cells, which reveals an obligatory role of NAADP in the control of VWF secretion.

scholarly journals Effects of indoxyl sulfate on adherens junctions of endothelial cells and the underlying signaling mechanism

2012 ◽  
Vol 113 (3) ◽  
pp. 1034-1043 ◽  
Author(s):  
Yu-Sen Peng ◽  
Yen-Tung Lin ◽  
Ying Chen ◽  
Kuan-Yu Hung ◽  
Seu-Mei Wang
Keyword(s):  
Endothelial Cells ◽  
Adherens Junctions ◽  
Indoxyl Sulfate ◽  
Signaling Mechanism

Abstract 3377: Modulation of Vessel Stability by the ELR-negative Chemokine IP-10

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Richard J Bodnar ◽  
Cecelia C Yates ◽  
Xiaoping Du ◽  
Alan Wells
Keyword(s):  
Endothelial Cells ◽  
Wound Repair ◽  
Critical Role ◽  
Tissue Development ◽  
Platelet Factor ◽  
Signaling Mechanism ◽  
Extracellular Signaling ◽  
Vessel Stability

Angiogenesis plays a critical role in tissue development and wound repair. Regulation of the vascular tree is critical to organogenesis and neo-organogenesis. The initial vigorous vessel proliferation and arborization that occurs during tissue development and wound repair must be pruned to form mature tissue. The signals that trigger this vascular regression are still ill-defined. Mitotic endothelial cells express the CXC receptor 3 (CXCR3), which binds the ELR-negative chemokines IP-10 (CXCL10), platelet factor 4 (PF4, CXCL4), IP-9/I-TAC (CXCL11), and MIG (CXCL9), with IP-9 and IP-10 being expressed during the later remodeling phases of wound repair when vascular involution occurs. We hypothesized that not only does this signaling system limit angiogenesis, but that CXCR3 signaling also compromises endothelial cell tube integrity contributing to regression. Treatment of newly formed tubes/cords on Matrigel (in vitro) or vessels in a subcutaneous Matrigel plug (in vivo) with IP-10 in either presence or absence of VEGF caused a dissociation of the tubes and subsequent vascular involution. This followed CXCR3 induced cleavage of β3 integrin in endothelial cells. CXCR3 triggering of mu-calpain activity caused cleavage of the cytoplasmic tail of human β3 integrins at the calpain cleavage sites NPLY747 and TSTF754. IP-10 stimulation was also found to activate caspase 3, blockage of which prevented cell death but not tube dissociation. Thus, CXCR3 activation in newly formed vessels results in endothelial dissociation from matrix, followed by anoikis. This is the first direct evidence for an extracellular signaling mechanism through CXCR3 causing the dissociation of newly formed blood vessels. This study was supported by funds from VA Medical Research Program and National Institute of General Medical Sciences (NIH, USA).

Sphingosine 1-Phosphate Induces Angiogenesis: Its Angiogenic Action and Signaling Mechanism in Human Umbilical Vein Endothelial Cells

1999 ◽  
Vol 264 (3) ◽  
pp. 743-750 ◽  
Author(s):  
Ok-Hee Lee ◽  
Young-Mi Kim ◽  
You Mie Lee ◽  
Eun-Joung Moon ◽  
Doo-Jae Lee ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Signaling Mechanism ◽  
Human Umbilical Vein ◽  
Sphingosine 1 Phosphate ◽  
Umbilical Vein Endothelial Cells

Phosphatidylinositol 3-kinase γ mediates shear stress-dependent activation of JNK in endothelial cells

1998 ◽  
Vol 275 (5) ◽  
pp. H1898-H1904 ◽  
Author(s):  
Young-Mi Go ◽  
Heonyong Park ◽  
Matthew C. Maland ◽  
Victor M. Darley-Usmar ◽  
Borislav Stoyanov ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Phosphatidylinositol 3 Kinase ◽  
Signaling Mechanism ◽  
Jnk Pathway ◽  
Aortic Endothelial Cells ◽  
Dependent Form ◽  
Stress Dependent ◽  
Phosphatidylinositol 3

Shear stress differentially activates extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) by mechanisms involving Gαi2 and Gβ/γ proteins, respectively, in bovine aortic endothelial cells (BAEC). The early events in this signaling mechanism by which G proteins regulate ERK and JNK in response to shear stress have not been defined. Here we show that BAEC endogenously express a G protein-dependent form of phosphatidylinositol 3-kinase, PI3Kγ, and its activity is stimulated by shear stress. PI3Kγ activity was measured in vitro using BAEC that were transiently transfected with an epitope-tagged PI3Kγ (vsv-PI3Kγ). Exposure of BAEC to shear stress rapidly and transiently stimulated the activity of vsv-PI3Kγ (maximum by 15 s, with a return to basal after 1-min exposure to 5 dyn/cm2 shear stress). Activity of vsv-PI3Kγ was stimulated by shear stress intensities as low as 0.5 dyn/cm2. Treatment of BAEC with an inhibitor of PI3K, wortmannin, inhibited shear-dependent activation of JNK but had no effect on that of ERK. Furthermore, expression of a kinase-inactive mutant (PI3KγK799R) in BAEC inhibited the shear-dependent activation of JNK but not ERK. Taken together, these results suggest that PI3Kγ selectively regulates the shear-sensitive JNK pathway. This differential and novel signaling pathway may be responsible for coordinating various mechanosensitive events in endothelial cells.

scholarly journals DIFFERENCES IN MEMBRANE POTENTIAL SENSITIVITY TO POTASSIUM CHANNEL OPENERS AND HYPOXIA BETWEEN INTACT AND CULTURED ENDOTHELIAL CELLS

2009 ◽  
Vol 55 (1) ◽  
pp. 49-56
Author(s):  
A.I. Bondarenko ◽  
Keyword(s):  
Endothelial Cells ◽  
Membrane Potential ◽  
Cell Function ◽  
Cultured Cells ◽  
Rat Aorta ◽  
Resting Membrane Potential ◽  
Signaling Mechanism ◽  
Endothelial Cell Function ◽  
K Channels ◽  
Cultured Endothelial Cells

The influence of pinacidil, an activator of ATP-sensitive K+ channels, on the membrane potential of endothelial cells from intact rat aorta and cultured endothelial cells was investigated. Pinacidil evoked a slowly developing sustained hyperpolariza-tion of endothelial cells from isolated artery with the amplitude of 15±4 mV from the resting membrane potential of –4Ш мВ. In contrast, in cultured endothelial cells pinacidil was without response. Diazoxide, another activator of ATP-sensitive K+ channels, in half of the cultured cells tested, evoked a slowly developing sustained hyperpolarization with the amplitude of 3 mV. The rest of the cells studied did not respond by membrane potential changes to diazoxide. It was suggested that high sen­sitivity of the membrane potential of in situ endothelial cells to potassium channels openers may represent a potent signaling mechanism influencing endothelial cell function upon stimula­tion of vascular KATP channels.

Signaling mechanism of extracellular RNA in endothelial cells

2009 ◽  
Vol 23 (7) ◽  
pp. 2100-2109 ◽  
Author(s):  
Silvia Fischer ◽  
Miwako Nishio ◽  
Saskia C. Peters ◽  
Marlene Tschernatsch ◽  
Maureen Walberer ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Signaling Mechanism ◽  
Extracellular Rna
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