Vascular COX-2 modulates blood pressure and thrombosis in mice.

Science Translational Medicine
Ying YuG A FitzGerald

Abstract

Prostacyclin (PGI(2)) is a vasodilator and platelet inhibitor, properties consistent with cardioprotection. More than a decade ago, inhibition of cyclooxygenase-2 (COX-2) by the nonsteroidal anti-inflammatory drugs (NSAIDs) rofecoxib and celecoxib was found to reduce the amount of the major metabolite of PGI(2) (PGI-M) in the urine of healthy volunteers. This suggested that NSAIDs might cause adverse cardiovascular events by reducing production of cardioprotective PGI(2). This prediction was based on the assumption that the concentration of PGI-M in urine likely reflected vascular production of PGI(2) and that other cardioprotective mediators, especially nitric oxide (NO), were not able to compensate for the loss of PGI(2). Subsequently, eight placebo-controlled clinical trials showed that NSAIDs that block COX-2 increase adverse cardiovascular events. We connect tissue-specific effects of NSAID action and functional correlates in mice with clinical outcomes in humans by showing that deletion of COX-2 in the mouse vasculature reduces excretion of PGI-M in urine and predisposes the animals to both hypertension and thrombosis. Furthermore, vascular disruption of COX-2 depressed expression of endothelial NO synthase and the conseq...Continue Reading

References

Aug 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·T Hla, K Neilson
Jan 6, 1999·Proceedings of the National Academy of Sciences of the United States of America·B F McAdamG A FitzGerald
Feb 13, 2001·Developmental Biology·Y Y KisanukiM Yanagisawa
Apr 20, 2002·Science·Yan ChengGarret A FitzGerald
Jul 3, 2002·The Journal of Clinical Investigation·Zhonghua QiMatthew D Breyer
Dec 1, 2004·Proceedings of the National Academy of Sciences of the United States of America·Joseph M MianoRavi P Misra
Mar 25, 2005·Genesis : the Journal of Genetics and Development·John J LeporeMichael S Parmacek
Jan 6, 2006·The Journal of Clinical Investigation·Tilo GrosserGarret A FitzGerald
Apr 15, 2006·The Journal of Clinical Investigation·Yan ChengGarret A Fitzgerald
Dec 5, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jane A MitchellTimothy D Warner
Feb 6, 2007·Trends in Pharmacological Sciences·Nicholas A Flavahan
Jun 19, 2007·Trends in Pharmacological Sciences·Garret A FitzGerald
Feb 23, 2008·Circulation Research·Sven T PlegerPatrick Most
Apr 21, 2009·Proceedings of the National Academy of Sciences of the United States of America·Dairong WangGarret A FitzGerald
Jan 12, 2010·Annual Review of Medicine·Tilo GrosserGarret A Fitzgerald
Jan 23, 2010·Cardiovascular & Hematological Disorders Drug Targets·Florian Krötz, Lena Struthmann
Feb 2, 2010·Clinical Journal of Oncology Nursing·Cynthia F Cramer
Apr 12, 2012·Proceedings of the National Academy of Sciences of the United States of America·Zhou YuGarret A FitzGerald

❮ Previous
Next ❯

Citations

Jun 13, 2013·Prostaglandins, Leukotrienes, and Essential Fatty Acids·I GomezX Norel
Aug 6, 2013·Nature Neuroscience·Daniel J HermansonSachin Patel
Oct 10, 2012·Proceedings of the National Academy of Sciences of the United States of America·Nicholas S KirkbyJane A Mitchell
Jan 8, 2013·Proceedings of the National Academy of Sciences of the United States of America·Emanuela RicciottiGarret A Fitzgerald
Feb 26, 2013·Proceedings of the National Academy of Sciences of the United States of America·Jane A Mitchell, Timothy D Warner
Apr 9, 2013·The Journal of Infectious Diseases·Juraj Ivanyi, Alimuddin Zumla
Jun 16, 2012·Science·Christopher P Cannon, Paul J Cannon
Oct 12, 2013·Antioxidants & Redox Signaling·Marios MargaritisCharalambos Antoniades
Jun 6, 2014·European Heart Journal·Francesco Cipollone, Donato Santovito
May 23, 2014·Trends in Pharmacological Sciences·Daniel J HermansonSachin Patel
May 7, 2014·European Heart Journal·Stephanie RossGuillaume Paré
Jan 28, 2014·The Journal of Allergy and Clinical Immunology·Kameran DahamBarbro Dahlén
Jan 16, 2016·Zeitschrift für Rheumatologie·W W BoltenUNKNOWN Kommission Pharmakotherapie der DGRh
Feb 24, 2016·Critical Reviews in Oncology/hematology·Ana BobanCedric Hermans
Jan 8, 2016·The Journal of Pharmacology and Experimental Therapeutics·Srinivasan ChandrasekharMatthew J Fisher
May 21, 2013·Nutrition Research·Maria Elizabeth Pereira NobreGlauce Socorro de Barros Viana
Oct 8, 2015·Clinical and Experimental Pharmacology & Physiology·Shasha LiYingbi Zhou
Nov 10, 2012·Rheumatic Diseases Clinics of North America·Susan M Goodman, Stephen Paget
Sep 18, 2012·Prostaglandins & Other Lipid Mediators·Lihong ChenTilo Grosser
Oct 10, 2012·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Nathan S Bryan
Jul 23, 2015·Prostaglandins & Other Lipid Mediators·Karsten Schrör, Bernhard H Rauch
Aug 15, 2015·Thrombosis and Haemostasis·Silvia S BarbieriElena Tremoli
Apr 17, 2013·Journal of Periodontal Research·R T MendesD Fernandes
Nov 21, 2012·Journal of Evaluation in Clinical Practice·Timothy T PhamJeremy L Johnson
Mar 30, 2016·European Journal of Pharmacology·Wenhong LuoYingbi Zhou
Apr 23, 2016·Atherosclerosis·Francesca SantilliFrancesco Cipollone
Jul 8, 2015·Journal of Thrombosis and Haemostasis : JTH·S RossG Paré
Sep 30, 2014·Biochimica Et Biophysica Acta·Paola Patrignani, Carlo Patrono
Jul 19, 2015·Vascular Pharmacology·Wen-Dong Li, Xiao-Qiang Li
Nov 28, 2013·The American Journal of Medicine·Payal KohliUNKNOWN REACH Registry Investigators
Jun 19, 2016·British Journal of Clinical Pharmacology·Carlo Patrono
Sep 7, 2016·Oxidative Medicine and Cellular Longevity·Guangrui Yang, Lihong Chen
Sep 3, 2016·International Journal of Cardiology·Rajeshwary GhoshAldrin V Gomes
Sep 22, 2016·Molecular Informatics·Francesca GrisoniGisbert Schneider
Jul 12, 2017·Journal of Clinical Pharmacy and Therapeutics·J HanV R Gordeuk

❮ Previous
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