Cyclooxygenases, microsomal prostaglandin E synthase-1, and cardiovascular function.

The Journal of Clinical Investigation
Yan ChengGarret A Fitzgerald

Abstract

We investigated the mechanisms by which inhibitors of prostaglandin G/H synthase-2 (PGHS-2; known colloquially as COX-2) increase the incidence of myocardial infarction and stroke. These inhibitors are believed to exert both their beneficial and their adverse effects by suppression of PGHS-2-derived prostacyclin (PGI(2)) and PGE(2). Therefore, the challenge remains to identify a mechanism whereby PGI(2) and PGE(2) expression can be suppressed while avoiding adverse cardiovascular events. Here, selective inhibition, knockout, or mutation of PGHS-2, or deletion of the receptor for PGHS-2-derived PGI(2), was shown to accelerate thrombogenesis and elevate blood pressure in mice. These responses were attenuated by COX-1 knock down, which mimics the beneficial effects of low-dose aspirin. PGE(2) biosynthesis is catalyzed by the coordinate actions of COX enzymes and microsomal PGE synthase-1 (mPGES-1). We show that deletion of mPGES-1 depressed PGE(2) expression, augmented PGI(2) expression, and had no effect on thromboxane biosynthesis in vivo. Most importantly, mPGES-1 deletion affected neither thrombogenesis nor blood pressure. These results suggest that inhibitors of mPGES-1 may retain their antiinflammatory efficacy by depressing...Continue Reading

References

Jun 1, 1995·Arteriosclerosis, Thrombosis, and Vascular Biology·J D EmeryJ B Lawrence
Jan 6, 1999·Proceedings of the National Academy of Sciences of the United States of America·B F McAdamG A FitzGerald
Feb 25, 1999·Canadian Journal of Physiology and Pharmacology·B P Booth, H L Fung
Jun 8, 1999·The Journal of Clinical Investigation·S L TilleyB H Koller
Aug 7, 1999·The Journal of Biological Chemistry·L J MarnettC A Lanzo
Jun 14, 2000·European Journal of Pharmacology·S MomiP Gresele
Aug 31, 2000·Annual Review of Biochemistry·W L SmithR M Garavito
Mar 10, 2001·The Journal of Clinical Investigation·J E FabreB H Koller
Dec 26, 2001·The New England Journal of Medicine·F Catella-LawsonG A FitzGerald
Apr 3, 2002·JAMA : the Journal of the American Medical Association·Peter F BodaryDaniel T Eitzman
Apr 20, 2002·Science·Yan ChengGarret A FitzGerald
Jul 3, 2002·The Journal of Clinical Investigation·G A FitzGerald
Aug 22, 2002·The Journal of Clinical Investigation·Charles D LoftinRobert Langenbach
Jan 16, 2003·Seminars in Arthritis and Rheumatism·D Craig Brater
Mar 22, 2003·The Journal of Pharmacology and Experimental Therapeutics·Tomoko TakanoLamine Aoudjit
Jul 2, 2003·Proceedings of the National Academy of Sciences of the United States of America·Catherine E TrebinoLaurent P Audoly
Dec 12, 2003·Nature Reviews. Drug Discovery·Garret A FitzGerald
Jan 21, 2004·Hypertension·Hui-Fang Cheng, Raymond C Harris
Apr 17, 2004·Kidney International·André SchneiderMatthew D Breyer
Oct 8, 2004·The New England Journal of Medicine·Garret A Fitzgerald
Dec 4, 2004·Arteriosclerosis, Thrombosis, and Vascular Biology·Barbara PiniGarret A FitzGerald
Dec 23, 2004·American Journal of Physiology. Renal Physiology·Tianxin YangJosephine P Briggs
Jan 7, 2005·Circulation Journal : Official Journal of the Japanese Circulation Society·Hidetsuna WatanabeTsuyoshi Watanabe
Jan 19, 2005·Circulation·Curt D FurbergGarret A FitzGerald
Feb 9, 2005·Hypertension·Jennifer C SullivanJennifer S Pollock
Feb 16, 2005·Archives of Internal Medicine·Tai-Juan AwHenry Krum
Feb 22, 2005·The Journal of Biological Chemistry·Catherine E TrebinoLaurent P Audoly
Mar 19, 2005·The Journal of Clinical Investigation·Ying YuColin D Funk
Jul 15, 2005·PLoS Medicine·Elizabeth J Westgate, Garret A Fitzgerald
Sep 13, 2005·Cell Metabolism·Helene FrancoisThomas M Coffman
Nov 29, 2005·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·B TunctanU Atik
Jan 6, 2006·The Journal of Clinical Investigation·Tilo GrosserGarret A FitzGerald

❮ Previous
Next ❯

Citations

Mar 17, 2007·Current Hypertension Reports·Chiara CuccurulloFrancesco Cipollone
Aug 26, 2006·Nature Clinical Practice. Rheumatology·Johannes W J Bijlsma
Dec 14, 2007·The New England Journal of Medicine·Giovanni Davì, Carlo Patrono
Apr 21, 2009·Proceedings of the National Academy of Sciences of the United States of America·Dairong WangGarret A FitzGerald
Apr 12, 2012·Proceedings of the National Academy of Sciences of the United States of America·Zhou YuGarret A FitzGerald
Oct 10, 2012·Proceedings of the National Academy of Sciences of the United States of America·Nicholas S KirkbyJane A Mitchell
Sep 18, 2009·The Journal of Biological Chemistry·Masayuki WadaWilliam L Smith
Jan 24, 2007·The Journal of Experimental Medicine·Sabrina GrossJean-Etienne Fabre
Oct 31, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hideki FuruyaToshihiko Kawamori
Nov 22, 2007·Journal of Cardiovascular Pharmacology·Colin D Funk, Garret A FitzGerald
Apr 19, 2011·Journal of Cardiovascular Pharmacology·Sawsan A ZaitoneNaglaa F El-Orabi
Nov 11, 2010·Pharmacogenetics and Genomics·Caroline F ThornRuss B Altman
Apr 8, 2010·The Journal of Pharmacology and Experimental Therapeutics·Miao WangGarret A FitzGerald
May 4, 2012·Science Translational Medicine·Ying YuGarret A FitzGerald
Jan 12, 2010·Annual Review of Medicine·Tilo GrosserGarret A Fitzgerald
Nov 15, 2006·Annual Review of Medicine·Yong I Cha, Raymond N DuBois
Mar 26, 2010·American Journal of Physiology. Renal Physiology·Zhanjun JiaTianxin Yang
Oct 24, 2009·Arteriosclerosis, Thrombosis, and Vascular Biology·Luis VilaJosé-Manuel Soria
Jun 5, 2010·Arteriosclerosis, Thrombosis, and Vascular Biology·Salam IbrahimEmer M Smyth
Nov 20, 2012·Arteriosclerosis, Thrombosis, and Vascular Biology·Salam IbrahimEmer M Smyth
Jun 10, 2010·Circulation·Yiqun HuiGarret A FitzGerald
Feb 2, 2011·Circulation·Miao WangGarret A Fitzgerald
Apr 4, 2009·American Journal of Respiratory and Critical Care Medicine·Bi-Sen DingVladimir R Muzykantov
Mar 13, 2012·The Journal of Clinical Investigation·Wen-Liang SongGarret A FitzGerald
Jul 29, 2006·Arthritis Research & Therapy·Marjolaine GossetClaire Jacques
Dec 20, 2008·Journal of Lipid Research·Emer M SmythGarret A FitzGerald
Feb 7, 2012·Inflammation and Regeneration·Fumiaki KojimaLeslie J Crofford
Oct 26, 2011·Future Medicinal Chemistry·Hui-Hua Chang, Emmanuelle J Meuillet
Jun 15, 2010·Clinical Lipidology·Emer M Smyth
Sep 16, 2006·Proceedings of the National Academy of Sciences of the United States of America·Miao WangGarret A FitzGerald
Apr 23, 2014·Proceedings of the National Academy of Sciences of the United States of America·Lihong ChenGarret A Fitzgerald
Oct 3, 2009·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Markus van der GietUwe J F Tietge
Nov 19, 2013·Pharmaceutical Patent Analyst·Jessica K NorbergEmmanuelle J Meuillet
Nov 1, 2011·Clinical and Experimental Nephrology·Noritaka KawadaYoshitaka Isaka

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
biopsy

Software Mentioned

BP
Dataquest LabPRO
GraphPad Prism

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
Miao WangGarret A Fitzgerald
The New England Journal of Medicine
Robert S BresalierAdenomatous Polyp Prevention on Vioxx (APPROVe) Trial Investigators
Proceedings of the National Academy of Sciences of the United States of America
Catherine E TrebinoLaurent P Audoly
© 2022 Meta ULC. All rights reserved