Pleiotropic effects of the hemostatic system

Journal of Thrombosis and Haemostasis : JTH
B M M KremersHenri M H Spronk

Abstract

Atherothrombosis is characterized by the inflammatory process of atherosclerosis combined with a hypercoagulable state leading to superimposed thrombus formation. In atherosclerotic plaques, cell signaling can be processed by protease activated receptors (PARs), four of which have been identified thus far (PAR1-4). Proteases that are able to activate PARs can be produced systemically, but also at the site of lesions, including thrombin and Factor Xa. After PAR activation, downstream signaling can lead to both pro-inflammatory effects and a hypercoagulable state. Which specific effect occurs, depends on the type of protease and activated PAR, and site of activation. Hypercoagulable effects are mainly exerted through PAR1 and PAR4, while pro-inflammatory responses are mostly seen after PAR1 and PAR2 activation. PAR signaling pathways contribute to atherothrombosis, suggesting that inhibition of these pathways possibly prevents cardiovascular events based on this pathophysiological mechanism. In this review, we highlight the pathways by which PAR activation leads to pro-inflammatory responses and a hypercoagulable state. Furthermore, we will give an overview of potential pharmacological treatment targets that promote vascular prot...Continue Reading

References

Apr 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·J N WilcoxD Gordon
Jul 1, 1997·Journal of Vascular Research·K EmilssonJ Sundelin
Jan 22, 1998·Biochemical and Biophysical Research Communications·F BonoJ M Herbert
Aug 26, 1998·Nature·M L KahnS R Coughlin
Mar 17, 1999·The Journal of Clinical Investigation·M L KahnS R Coughlin
Mar 4, 2000·The Journal of Biological Chemistry·G R SambranoS R Coughlin
May 11, 2000·Proceedings of the National Academy of Sciences of the United States of America·E CamererS R Coughlin
Aug 8, 2001·The Journal of Cell Biology·S LindemannA S Weyrich
Jan 25, 2002·Annals of the New York Academy of Sciences·J N WilcoxM E Rasmussen
Oct 9, 2002·The Journal of Experimental Medicine·Steffen MassbergMeinrad Gawaz
Sep 12, 2003·The New England Journal of Medicine·Elaine M HylekDaniel E Singer
Feb 20, 2004·The Journal of Biological Chemistry·Todd M QuintonSatya P Kunapuli
Jul 22, 2004·Blood·Leon J SchurgersJan Janzen
Sep 17, 2004·Molecular Pharmacology·Susan F Steinberg
Jan 25, 2005·The Journal of Biological Chemistry·Matthew J LudemanShaun R Coughlin
Apr 23, 2005·Arteriosclerosis, Thrombosis, and Vascular Biology·Jeffrey F W KeurenTheo Lindhout
Dec 31, 2005·Arteriosclerosis, Thrombosis, and Vascular Biology·Rachel E TilleyNigel Mackman
Mar 25, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·Masafumi KuzuyaAkihisa Iguchi
Sep 23, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·Florian BeaErwin Blessing
Mar 7, 2007·Seminars in Thrombosis and Hemostasis·Dorothea I Siegel-Axel, Meinrad Gawaz
Apr 28, 2007·Arteriosclerosis, Thrombosis, and Vascular Biology·Robert K AndrewsMichael C Berndt
Jun 28, 2007·Biochemistry·Marvin T Nieman, Alvin H Schmaier
Sep 9, 2008·Trends in Molecular Medicine·Keren BorensztajnC Arnold Spek
Feb 21, 2009·Cardiovascular Research·Julian Ilcheff BorissoffHugo ten Cate
Sep 1, 2009·The New England Journal of Medicine·Stuart J ConnollyUNKNOWN RE-LY Steering Committee and Investigators
Aug 11, 2010·Circulation·Julian Ilcheff BorissoffHenri M H Spronk
Feb 12, 2011·The New England Journal of Medicine·Stuart J ConnollyUNKNOWN AVERROES Steering Committee and Investigators
May 4, 2011·Proceedings of the National Academy of Sciences of the United States of America·Leila M SevignyAthan Kuliopulos
Jun 23, 2011·Journal of Thrombosis and Haemostasis : JTH·D R FabriV R Arruda
Jul 26, 2011·The New England Journal of Medicine·John H AlexanderUNKNOWN APPRAISE-2 Investigators
Aug 13, 2011·The New England Journal of Medicine·Manesh R PatelUNKNOWN ROCKET AF Investigators
Sep 9, 2011·Thrombosis and Haemostasis·H D Manthey, A Zernecke

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Citations

Nov 19, 2019·Hematology·Delphine BorgelFrançois Saller
Jan 4, 2019·Clinical Research in Cardiology : Official Journal of the German Cardiac Society·Lisa EggebrechtPhilipp Sebastian Wild
Dec 4, 2020·Neural Regeneration Research·Elena Pompili, Cinzia Fabrizi
Aug 3, 2021·Evidence-based Complementary and Alternative Medicine : ECAM·Zhen LeiHong Wu

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