scholarly journals Polyploidy impairs human aortic endothelial cell function and is prevented by nicotinamide phosphoribosyltransferase

2010 ◽  
Vol 298 (1) ◽  
pp. C66-C74 ◽  
Author(s):  
Nica M. Borradaile ◽  
J. Geoffrey Pickering
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Replicative Senescence ◽  
Cell Function ◽  
Human Aortic Endothelial Cell ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Endothelial Cell Function ◽  
Aortic Endothelial Cells ◽  
Human Aortic Endothelial Cells ◽  
Aortic Endothelial

Polyploid endothelial cells are found in aged and atherosclerotic arteries. However, whether increased chromosome content has an impact on endothelial cell function is unknown. We show here that human aortic endothelial cells become tetraploid as they approach replicative senescence. Furthermore, accumulation of tetraploid endothelial cells was accelerated during growth in high glucose. Interestingly, induction of polyploidy was completely prevented by modest overexpression of the NAD+ regenerating enzyme, nicotinamide phosphoribosyltransferase (Nampt). To determine the impact of polyploidy on endothelial cell function, independent of replicative senescence, we induced tetraploidy using the spindle poison, nocodazole. Global gene expression analyses of tetraploid endothelial cells revealed a dysfunctional phenotype characterized by a cell cycle arrest profile (decreased CCNE2/A2, RBL1, BUB1B; increased CDKN1A) and increased expression of genes involved in inflammation ( IL32, TNFRSF21/10C, PTGS1) and extracellular matrix remodeling ( COL5A1, FN1, MMP10/14). The protection from polyploidy conferred by Nampt was not associated with enhanced poly(ADP-ribose) polymerase-1 or sirtuin (SIRT) 2 activity, but with increased SIRT1 activity, which reduced cellular reactive oxygen species and the associated oxidative stress stimulus for the induction of polyploidy. We conclude that human aortic endothelial cells are prone to chromosome duplication that, in and of itself, can induce characteristics of endothelial dysfunction. Moreover, the emergence of polyploid endothelial cells during replicative aging and glucose overload can be prevented by optimizing the Nampt-SIRT1 axis.

scholarly journals Role of lipid phosphate phosphatase 3 in human aortic endothelial cell function

2016 ◽  
Vol 112 (3) ◽  
pp. 702-713 ◽  
Author(s):  
Zahia Touat-Hamici ◽  
Henri Weidmann ◽  
Yuna Blum ◽  
Carole Proust ◽  
Hervé Durand ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Function ◽  
Human Aortic Endothelial Cell ◽  
Endothelial Cell Function ◽  
Aortic Endothelial Cell ◽  
Lipid Phosphate ◽  
Aortic Endothelial

Differential activation of NF-kappa B in human aortic endothelial cells conditioned to specific flow environments

1997 ◽  
Vol 273 (2) ◽  
pp. C572-C578 ◽  
Author(s):  
S. Mohan ◽  
N. Mohan ◽  
E. A. Sprague
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
High Shear ◽  
Monocyte Adhesion ◽  
Nf Kappa B ◽  
Differential Activation ◽  
Aortic Endothelial Cells ◽  
Human Aortic Endothelial Cells ◽  
Low Shear ◽  
Aortic Endothelial

Endothelial cell-monocyte interaction plays an important role in atherogenesis. The expressions of some endothelial cell adhesion molecules involved in endothelial cell-monocyte interactions are regulated by transcription factor NF-kappa B. Because low shear stress has been known to influence endothelial monocyte adhesion, the differential activation of NF-kappa B under different flow regimens across time (0.5-24 h) was investigated. Nuclear proteins from flow-conditioned human aortic endothelial cells (HAEC) were analyzed by electrophoretic mobility shift assay using [gamma-32P]dATP-labeled NF-kappa B-specific oligonucleotide. Our results demonstrated that NF-kappa B activation was significantly elevated in HAEC exposed to prolonged (> 2 h) steady low shear (2 dyn/cm2) and pulsatile low shear (2 +/- 2 dyn/cm2) compared with HAEC exposed to high shear (16 dyn/cm2). In contrast, at 30 min, high shear-exposed HAEC exhibited an early, transient increase in NF-kappa B activity, relative to low shear-exposed cells, which reversed on continued exposure to high shear. Maximum activity in both low shear- and pulsatile low shear-conditioned HAEC was observed at 16 h compared with HAEC exposed to prolonged high shear. These results indicate that exposure of HAEC to prolonged low shear conditions is associated with significantly increased and prolonged NF-kappa B activity. This observation might provide a mechanism to explain the increased monocyte adhesion in atherosclerosisprone arterial sites exposed to chronic low-shear flow patterns.

scholarly journals Epsins Negatively Regulate Aortic Endothelial Cell Function by Augmenting Inflammatory Signaling

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1918
Author(s):  
Yunzhou Dong ◽  
Beibei Wang ◽  
Kui Cui ◽  
Xiaofeng Cai ◽  
Sudarshan Bhattacharjee ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Activation ◽  
Adaptor Proteins ◽  
Endothelial Cell Activation ◽  
Calcium Release Channel ◽  
Inflammatory Signaling ◽  
Endothelial Cell Function ◽  
Aortic Endothelial Cells ◽  
Aortic Endothelial

Background: The endothelial epsin 1 and 2 endocytic adaptor proteins play an important role in atherosclerosis by regulating the degradation of the calcium release channel inositol 1,4,5-trisphosphate receptor type 1 (IP3R1). In this study, we sought to identify additional targets responsible for epsin-mediated atherosclerotic endothelial cell activation and inflammation in vitro and in vivo. Methods: Atherosclerotic ApoE−/− mice and ApoE−/− mice with an endothelial cell-specific deletion of epsin 1 on a global epsin 2 knock-out background (EC-iDKO/ApoE−/−), and aortic endothelial cells isolated from these mice, were used to examine inflammatory signaling in the endothelium. Results: Inflammatory signaling was significantly abrogated by both acute (tumor necrosis factor-α (TNFα) or lipopolysaccharide (LPS)) and chronic (oxidized low-density lipoprotein (oxLDL)) stimuli in EC-iDKO/ApoE−/− mice and murine aortic endothelial cells (MAECs) isolated from epsin-deficient animals when compared to ApoE−/− controls. Mechanistically, the epsin ubiquitin interacting motif (UIM) bound to Toll-like receptors (TLR) 2 and 4 to potentiate inflammatory signaling and deletion of the epsin UIM mitigated this interaction. Conclusions: The epsin endocytic adaptor proteins potentiate endothelial cell activation in acute and chronic models of atherogenesis. These studies further implicate epsins as therapeutic targets for the treatment of inflammation of the endothelium associated with atherosclerosis.

scholarly journals Collagen-mimetic hydrogels promote human endothelial cell adhesion, migration and phenotypic maturation

2015 ◽  
Vol 3 (40) ◽  
pp. 7912-7919 ◽  
Author(s):  
Dany J. Munoz-Pinto ◽  
Viviana R. Guiza-Arguello ◽  
Silvia M. Becerra-Bayona ◽  
Josh Erndt-Marino ◽  
Satyavrata Samavedi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Endothelial Cell ◽  
Human Endothelial Cell ◽  
Aortic Endothelial Cells ◽  
Hydrogel Coatings ◽  
Human Aortic Endothelial Cells ◽  
Endothelial Cell Adhesion ◽  
Aortic Endothelial

This work evaluates the response of human aortic endothelial cells (HAECs) to thromboresistant collagen-mimetic hydrogel coatings.

CRP promotes monocyte-endothelial cell adhesion via Fcγ receptors in human aortic endothelial cells under static and shear flow conditions

2006 ◽  
Vol 291 (3) ◽  
pp. H1170-H1176 ◽  
Author(s):  
Sridevi Devaraj ◽  
Benjamin Davis ◽  
Scott I. Simon ◽  
Ishwarlal Jialal
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Endothelial Cell ◽  
Shear Flow ◽  
Fcγ Receptors ◽  
Aortic Endothelial Cells ◽  
Static Conditions ◽  
Human Aortic Endothelial Cells ◽  
Endothelial Cell Adhesion ◽  
Aortic Endothelial

Monocyte-endothelial cell adhesion is a key early event in atherogenesis. C-reactive protein (CRP), a cardiovascular risk marker, is known to stimulate ICAM and VCAM in human aortic endothelial cells (HAEC) and induces monocyte-endothelial cell adhesion. In this study, we examined the mechanisms by which native CRP promotes monocyte-endothelial cell adhesion under static conditions and tested the effect of CRP on adhesion under shear flow. Incubation of HAEC with CRP (>25 μg/ml) upregulated NF-κB activity, and this resulted in a significant increase in ICAM (54% increase, P < 0.001), VCAM (41% increase, P < 0.01), and monocyte-endothelial cell adhesion (44% increase, P < 0.02) compared with those of control. Preincubation with antibodies to CD32 and CD64 but not CD16 effectively inhibited this activation. Blocking NF-κB activity with inhibitors or a dominant negative inhibitory κB significantly decreased ICAM, VCAM upregulation, and subsequent monocyte-endothelial cell adhesion. Preincubation with antibodies to CD32 and CD64 or transient transfection with small interference RNA to CD32 attenuated CRP-induced NF-κB activity, ICAM, VCAM, and monocyte-endothelial cell adhesion under static conditions. Also, the Syk kinase inhibitor piceatannol and MG-132, a proteasome degradation inhibitor, produced similar attenuation in NF-κB activity, ICAM, VCAM, and adhesion. Furthermore, CRP-activated endothelial cells supported monocyte rolling, arrest, and transmigration in shear flow (2 dyn/cm2), and this was also inhibited by preincubation with antibodies to CD32 and CD64. Thus, in HAEC, CRP upregulates monocyte-endothelial adhesion by activation of NF-κB through engaging the Fcγ receptors CD32 and CD64.

scholarly journals Differential effects of hydrogen peroxide on indices of endothelial cell function.

1984 ◽  
Vol 159 (2) ◽  
pp. 592-603 ◽  
Author(s):  
A Ager ◽  
J L Gordon
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Xanthine Oxidase ◽  
Cell Function ◽  
Threshold Concentration ◽  
Endothelial Cell Function ◽  
Aortic Endothelial Cells ◽  
Prostaglandin Production ◽  
Chromium Release ◽  
Sublethal Doses

The responses of pig aortic endothelial cells to sublethal doses of potentially toxic stimuli were investigated by monitoring K+ efflux, prostaglandin production, and the release of cytoplasmic purines. Xanthine plus xanthine oxidase reversibly stimulated these three parameters of endothelial cell function at doses that were not cytotoxic, as measured by chromium release, adenine uptake, and vital dye exclusion. The effects of xanthine plus xanthine oxidase were inhibited by catalase but not by superoxide dismutase, suggesting that H2O2 was responsible. Reagent H2O2 also reversibly stimulated K+ efflux, prostaglandin production, and the release of purines. The threshold concentration of H2O2 for these effects was approximately 10 microM, which was at least 30-fold lower than that which caused cytotoxicity. In addition to the direct effect of H2O2 in stimulating prostaglandin production (PGI2 and PGE2), prior exposure of endothelial cells to lower doses of H2O2 (less than 0.1 microM) at high oxygen tension inhibited the subsequent stimulation of prostaglandin production by ATP, A23187, and H2O2 itself. We conclude that H2O2 has substantial effects on endothelial physiology at doses up to 3,000-fold lower than those which induce cytotoxicity.

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