Activation of proteinase-activated receptor 2 stimulates soluble vascular endothelial growth factor receptor 1 release via epidermal growth factor receptor transactivation in endothelial cells.

Hypertension
Bahjat Al-AniAsif Ahmed

Abstract

The proteinase-activated receptor 2 (PAR-2) expression is increased in endothelial cells derived from women with preeclampsia, characterized by widespread maternal endothelial damage, which occurs as a consequence of elevated soluble vascular endothelial growth factor receptor-1 (sVEGFR-1; commonly known as sFlt-1) in the maternal circulation. Because PAR-2 is upregulated by proinflammatory cytokines and activated by blood coagulation serine proteinases, we investigated whether activation of PAR-2 contributed to sVEGFR-1 release. PAR-2-activating peptides (SLIGRL-NH(2) and 2-furoyl-LIGRLO-NH(2)) and factor Xa increased the expression and release of sVEGFR-1 from human umbilical vein endothelial cells. Enzyme-specific, dominant-negative mutants and small interfering RNA were used to demonstrate that PAR-2-mediated sVEGFR-1 release depended on protein kinase C-beta(1) and protein kinase C-epsilon, which required intracellular transactivation of epidermal growth factor receptor 1, leading to mitogen-activated protein kinase activation. Overexpression of heme oxygenase 1 and its gaseous product, carbon monoxide, decreased PAR-2-stimulated sVEGFR-1 release from human umbilical vein endothelial cells. Simvastatin, which upregulates h...Continue Reading

References

Jun 30, 1997·FEBS Letters·N Osherov, A Levitzki
Oct 18, 2000·American Journal of Obstetrics and Gynecology·M BaumD S Seidman
Aug 6, 2002·The Journal of Clinical Endocrinology and Metabolism·Yuping WangMichael J Lucas
Jan 11, 2003·The Journal of Biological Chemistry·Abdelkarim SabriSusan F Steinberg
Dec 25, 2004·Hypertension in Pregnancy : Official Journal of the International Society for the Study of Hypertension in Pregnancy·J Moodley
Feb 16, 2006·The Journal of Experimental Medicine·Farshid NoorbakhshChristopher Power
Sep 8, 2006·The New England Journal of Medicine·Richard J LevineUNKNOWN CPEP Study Group
May 8, 2007·Journal of Reproductive Immunology·I L SargentC W G Redman
Jul 20, 2007·Clinical and Applied Thrombosis/hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis·Lothar HeilmannKunhard Pollow
Oct 4, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Amir Afkhami-GoliChristopher Power
Nov 3, 2007·BMJ : British Medical Journal·Leanne BellamyDavid J Williams
Nov 23, 2007·American Journal of Physiology. Gastrointestinal and Liver Physiology·Jacques Q van der MerweWallace K MacNaughton
Dec 18, 2007·American Journal of Physiology. Lung Cellular and Molecular Physiology·Theo J MoraesGregory P Downey
Jun 24, 2008·The Journal of Maternal-fetal & Neonatal Medicine : the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians·Offer ErezChong Jai Kim

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Citations

Apr 25, 2012·Der Nervenarzt·F SextroG F Hamann
Nov 1, 2012·Bulletin of Experimental Biology and Medicine·S M TolpygoA V Kotov
Mar 19, 2013·The Journal of Biological Chemistry·Matthew S WaitkusPaul E DiCorleto
Jan 22, 2011·Expert Opinion on Therapeutic Targets·Keren Borensztajn, C Arnold Spek
Nov 14, 2015·Annual Review of Pharmacology and Toxicology·Steven J ForresterSatoru Eguchi
Jan 27, 2011·Seminars in Nephrology·Sharon E Maynard, S Ananth Karumanchi
May 7, 2011·American Journal of Reproductive Immunology : AJRI·Tamara Y CarrollVikki M Abrahams
Jul 30, 2014·American Journal of Reproductive Immunology : AJRI·Stefan M GyslerVikki M Abrahams
Aug 7, 2013·Proceedings of the National Academy of Sciences of the United States of America·Jian-Wei QiLu-Yuan Li
Jul 31, 2013·Hypertension·Junie P WarringtonJoey P Granger
Jan 26, 2018·Obstetrical & Gynecological Survey·Enrique Esteve-ValverdeJaume Alijotas-Reig
Mar 7, 2021·International Journal of Molecular Sciences·Anne GrunenwaldMarie Frimat
Jun 11, 2021·Circulation Research·Meaghan E CollingYogendra Kanthi

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