Short-term sustained hyperglycaemia fosters an archetypal senescence-associated secretory phenotype in endothelial cells and macrophages

Receptor-operated effects of alpha-thrombin and of the thrombin receptor-activating peptide TRAP14 on cytoplasmic Ca2+ concentration ([Ca2+]i) were examined in fura 2-loaded endothelial cells. Experiments with hirudin showed that alpha-thrombin-induced Ca2+ influx requires the continuous presence of active alpha-thrombin. YFLLRNP, known to antagonize alpha-thrombin- and TRAP7-induced [Ca2+]i transients in platelets, did not antagonize [Ca2+]i transients in response to alpha-thrombin and TRAP14 in human umbilical vein endothelial cells (HUVEC). Repetitive short-term stimulations with alpha-thrombin desensitized [Ca2+]i transients to subsequent stimulations with either alpha-thrombin or TRAP14. In contrast, repeated short-term stimulations with TRAP14 sensitized [Ca2+]i transients to subsequent stimulations with either agonist. Blockade of Ca2+ influx by SKF-96365 abolished the sensitizing effect of TRAP14. The results indicate distinct characteristics of platelet and endothelial thrombin receptors and suggest that alpha-thrombin and TRAP14 activate the receptor differently. It appears that receptor desensitization occurs independently of TRAP14 binding and, hence, tethered ligand binding to and activation of the receptor. Persistent receptor desensitization after alpha-thrombin seems to depend on both alpha-thrombin binding to the hirudin-like receptor domain and the irreversible proteolytic cleavage of the receptor. It does not involve the TRAP14/tethered ligand binding site of the receptor. TRAP14 primes the receptor by a mechanism mediated by Ca2+ influx.

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Short-term high glucose exposure impairs insulin signaling in endothelial cells

Cardiovascular Diabetology ◽

10.1186/s12933-015-0278-0 ◽

2015 ◽

Vol 14 (1) ◽

Cited By ~ 26

Author(s):

Valeria De Nigris ◽

Gemma Pujadas ◽

Lucia La Sala ◽

Roberto Testa ◽

Stefano Genovese ◽

...

Keyword(s):

Endothelial Cells ◽

Insulin Signaling ◽

High Glucose ◽

Short Term ◽

Glucose Exposure

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Interferon-α prevents apoptosis of endothelial cells after short-term exposure but induces replicative senescence after continuous stimulation

Laboratory Investigation ◽

10.1038/labinvest.3700461 ◽

2006 ◽

Vol 86 (10) ◽

pp. 997-1007 ◽

Cited By ~ 31

Author(s):

Johannes Pammer ◽

Christine Reinisch ◽

Peter Birner ◽

Kristin Pogoda ◽

Michael Sturzl ◽

...

Keyword(s):

Endothelial Cells ◽

Replicative Senescence ◽

Interferon Α ◽

Short Term ◽

Continuous Stimulation ◽

Short Term Exposure

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Trabeculectomy Versus EX-PRESS Shunt Versus Ahmed Valve Implant: Short-term Effects on Corneal Endothelial Cells

American Journal of Ophthalmology ◽

10.1016/j.ajo.2015.11.012 ◽

2016 ◽

Vol 162 ◽

pp. 201-202 ◽

Cited By ~ 4

Author(s):

Halil Ates ◽

Melis Palamar ◽

Ayse Yagci ◽

Sait Egrilmez

Keyword(s):

Endothelial Cells ◽

Corneal Endothelial Cells ◽

Short Term ◽

Ahmed Valve ◽

Short Term Effects

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Effects of 2-Deoxy-d-Glucose on Proliferation of Vascular Smooth Muscle Cells and Endothelial Cells

Journal of International Medical Research ◽

10.1177/147323000803600515 ◽

2008 ◽

Vol 36 (5) ◽

pp. 986-991 ◽

Cited By ~ 9

Author(s):

HM Nef ◽

H Möllmann ◽

A Joseph ◽

C Troidl ◽

S Voss ◽

...

Keyword(s):

Endothelial Cells ◽

Smooth Muscle ◽

Smooth Muscle Cells ◽

Muscle Cells ◽

Inhibitory Effect ◽

Short Term ◽

Inhibition Of Proliferation ◽

Aortic Endothelial Cells ◽

Intracoronary Stenting ◽

Dose Dependent

2-Deoxy-d-glucose (2-DG) is a glucose analogue that has been proposed for cancer therapy due to its cytostatic properties. Its effect on the proliferation of smooth muscle cells and endothelial cells has not been fully clarified. The aims of this study were to investigate the effects of 2-DG on the proliferation of porcine aortic endothelial cells (PAEC) and porcine smooth muscle cells (PSMC), to establish an overview of its dose-dependent inhibitory capacity and to examine whether the short-term incubation of cells with 2-DG has an impact on cell proliferation in culture. Our results showed a dose-dependent significant inhibitory effect on proliferation, which was more pronounced in PSMC than in PAEC. Even after short-term incubation of cells with 2-DG, relevant inhibition of proliferation was documented. The clinical application of 2-DG might be a promising concept by inhibiting cells that show a potentially rapid proliferation in response to non-malignant stimuli, such as smooth muscle cells after intracoronary stenting.

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Norrin/Frizzled4 signalling in the preneoplastic niche blocks medulloblastoma initiation

eLife ◽

10.7554/elife.16764 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 10

Author(s):

Erin A Bassett ◽

Nicholas Tokarew ◽

Ema A Allemano ◽

Chantal Mazerolle ◽

Katy Morin ◽

...

Keyword(s):

Endothelial Cells ◽

Tumor Microenvironment ◽

Mouse Model ◽

Tumor Cells ◽

Tumor Stroma ◽

Cerebellar Tumor ◽

Short Term ◽

Stromal Component ◽

Tumor Types ◽

The Relationship

The tumor microenvironment is a critical modulator of carcinogenesis; however, in many tumor types, the influence of the stroma during preneoplastic stages is unknown. Here we explored the relationship between pre-tumor cells and their surrounding stroma in malignant progression of the cerebellar tumor medulloblastoma (MB). We show that activation of the vascular regulatory signalling axis mediated by Norrin (an atypical Wnt)/Frizzled4 (Fzd4) inhibits MB initiation in the Ptch+/− mouse model. Loss of Norrin/Fzd4-mediated signalling in endothelial cells, either genetically or by short-term blockade, increases the frequency of pre-tumor lesions and creates a tumor-permissive microenvironment at the earliest, preneoplastic stages of MB. This pro-tumor stroma, characterized by angiogenic remodelling, is associated with an accelerated transition from preneoplasia to malignancy. These data expose a stromal component that regulates the earliest stages of tumorigenesis in the cerebellum, and a novel role for the Norrin/Fzd4 axis as an endogenous anti-tumor signal in the preneoplastic niche.

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Migration of lymphocytes across specialized vascular endothelium. V. Production of a sulphated macromolecule by high endothelial cells in lymph nodes

Journal of Cell Science ◽

10.1242/jcs.57.1.277 ◽

1982 ◽

Vol 57 (1) ◽

pp. 277-292

Author(s):

P. Andrews ◽

D.W. Milsom ◽

W.L. Ford

Keyword(s):

Endothelial Cells ◽

Lymph Node ◽

Golgi Apparatus ◽

Lymph Nodes ◽

Vascular Endothelium ◽

Cervical Lymph Node ◽

Selective Extraction ◽

Short Term ◽

Cytoplasmic Vesicles

High endothelial cells lining the post capillary venules in the paracortical areas of rat lymph nodes were found by autoradiography to incorporate [35S]sulphate, whether it was injected into the footpad to reach the draining popliteal lymph node or added to short-term cultures of cervical lymph node slices. The early localization of [35S]sulphate was confined to the Golgi apparatus, but before it disappeared from the cell radioactivity was associated with cytoplasmic vesicles. Sulphated material in macromolecular form was extracted from lymph nodes that had been labelled in vivo and was also found in the supernatant of lymph node cultures. The labelled material was not proteoglycan in nature. High endothelial cells apparently secrete a sulphated macromolecule but its relationship to the only known function of high-walled endothelium—the selective extraction of lymphocytes from the blood—remains to be clarified.

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