Inflammation dysregulates Notch signaling in endothelial cells: implication of Notch2 and Notch4 to endothelial dysfunction

Biochemical Pharmacology
T QuillardBéatrice Charreau

Abstract

Although the involvement of the Notch pathway in several areas of vascular biology is now clearly established, its role in vascular inflammation at the endothelial level remains to be elucidated. In this study, we demonstrated that pro-inflammatory cytokines drive a specific regulation of the Notch pathway in vascular endothelial cells (ECs). In arterial ECs, TNFα strongly modulates the pattern of Notch expression by decreasing Notch4 expression while increasing Notch2 expression. Changes in Notch expression were associated with a reduction in hes1 and hey2 expression and in CBF1 reporter gene activity, suggesting that TNFα regulates both Notch expression and activity. Notch2 and Notch4 regulations occurred independently and were found to be mostly mediated by the NFκB signaling pathways and PI3-kinase signaling pathways, respectively. Functionally, TNF-mediated Notch regulation promotes caspase-dependent EC apoptosis. Finally, our findings confirmed that dysregulated Notch signaling also occurs upon inflammation in vivo and correlates with caspase activation and apoptosis. In conclusion, inflammatory cytokines elicit a switch in Notch expression characterized by Notch2 predominance over Notch4 leading to a reduced Notch activi...Continue Reading

References

Oct 1, 1990·Transplantation·J S Pober, R S Cotran
Oct 31, 1998·Current Opinion in Immunology·D M BriscoeA H Lichtman
Apr 10, 1999·Human Molecular Genetics·Y XueT Gridley
Apr 30, 1999·Science·S Artavanis-TsakonasR J Lake
Sep 24, 1999·Immunologic Research·J S Pober
Nov 9, 2000·The Journal of Biological Chemistry·A M HendersonC C Hughes
Jun 22, 2001·Experimental and Molecular Pathology·L A Madge, J S Pober
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Jan 28, 2003·Journal of Cellular Physiology·Tatsuya IsoYasuo Hamamori
Jun 10, 2003·Proceedings of the National Academy of Sciences of the United States of America·Emmanuelle SixFrederique Logeat
Sep 10, 2003·Proceedings of the National Academy of Sciences of the United States of America·Jen-Tsan ChiPatrick O Brown
Oct 23, 2003·Nature Reviews. Cancer·Freddy Radtke, Kenneth Raj
Nov 13, 2003·Molecular and Cellular Biology·Colleen M WittChristopher A Klug
Dec 13, 2003·Immunity·Ivan MaillardWarren S Pear
Jan 1, 2004·The Journal of Biological Chemistry·Farrell MacKenzieAly Karsan
Jul 13, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Catherine SweeneyPaul A Cahill
Nov 13, 2004·Proceedings of the National Academy of Sciences of the United States of America·Cristina AguileraAnna Bigas
Apr 6, 2005·Circulation·Florian P LimbourgJames K Liao
Oct 1, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Rafia S Al-LamkiJohn R Bradley
Nov 18, 2005·Blood·Kevin G Leong, Aly Karsan
Mar 31, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Zhao-Jun LiuMeenhard Herlyn
Dec 14, 2007·Proceedings of the National Academy of Sciences of the United States of America·Yan WuDaniel Kirchhofer
Jul 23, 2008·Perspectives in Vascular Surgery and Endovascular Therapy·Kimon Bekelis, Nicos Labropoulos
Aug 8, 2009·European Journal of Immunology·Eva MonsalveMaría José M Díaz-Guerra

❮ Previous
Next ❯

Citations

May 31, 2012·European Heart Journal·Paola RizzoRoberto Ferrari
Nov 5, 2013·Biochimica Et Biophysica Acta·Weiqiang ZhouShanchun Guo
Jul 31, 2012·Human Immunology·Béatrice Charreau
Dec 18, 2015·Thrombosis and Haemostasis·Stephanie Lehoux, Elizabeth A Jones
Nov 11, 2015·The Journal of Experimental Medicine·Anaïs BriotM Luisa Iruela-Arispe
Jul 20, 2014·The Journal of Thoracic and Cardiovascular Surgery·Nassrene Y ElmadhunFrank W Sellke
Feb 24, 2015·Journal of Cellular Biochemistry·Shambhavi NaikApurva Sarin
Aug 27, 2015·Current Opinion in Lipidology·Heinrich J Huber, Paul Holvoet
Jun 22, 2016·Ageing Research Reviews·Carmela Rita BalistreriCalogero Caruso
Mar 8, 2016·Journal of Cellular Physiology·Alessia OngaroMonica De Mattei
Dec 9, 2016·Cell Death & Disease·Chiara Fazio, Luigi Ricciardiello
Mar 28, 2013·International Journal of Molecular Sciences·Thibaut Quillard, Beatrice Charreau
Mar 17, 2018·Current Opinion in Hematology·Julia J Mack, M Luisa Iruela-Arispe
Dec 20, 2011·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Ming LiQinmei Ke
Aug 27, 2016·Arteriosclerosis, Thrombosis, and Vascular Biology·Toshiaki NakanoMasanori Aikawa
Mar 6, 2015·Scientific Reports·Gopalakrishnan RamakrishnanGuri Tzivion
Jul 20, 2014·American Journal of Physiology. Heart and Circulatory Physiology·Nicole M AshpoleWilliam E Sonntag
Apr 4, 2015·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Serafim KiriakidisMassimiliano Mazzone
Aug 2, 2017·International Journal of Molecular Sciences·Ding-Yuan TianYun Wang
May 26, 2018·Laboratory Investigation; a Journal of Technical Methods and Pathology·Jessica Davis-KnowltonLucy Liaw
Oct 9, 2019·International Journal of Molecular Sciences·Francesco Vieceli Dalla SegaSaverio Francesco Retta
Jan 10, 2020·Oxidative Medicine and Cellular Longevity·Giorgio AquilaPaola Rizzo
Jun 14, 2019·Frontiers in Immunology·Francesco Vieceli Dalla SegaPaola Rizzo
Jul 28, 2016·Current Opinion in Lipidology·Anaïs BriotM Luisa Iruela-Arispe
May 1, 2021·International Journal of Molecular Sciences·Rosaria Vincenza GiglioManfredi Rizzo
Jun 15, 2021·Frontiers in Cardiovascular Medicine·Randa M Breikaa, Brenda Lilly
Jul 24, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Sanghamitra SahooPatrick J Pagano
Aug 28, 2021·Biomedicines·Francesca FortiniRoberto Ferrari

❮ Previous
Next ❯

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

Cell Adhesion Molecules in AS

Cell adhesion molecules expressed on the vascular endothelium and circulating leukocytes in response to inflammatory stimuli are implicated in atherosclerosis. Here is the latest research.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Caspases in Metabolic Diseases

Caspases, the family of cysteine proteases are involved in programmed cell death, but their role in metabolic diseases, inflammation and immunity has been of interested. Discover the latest research on caspases in metabolic diseases here.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.