Rivaroxaban, a specific FXa inhibitor, improved endothelium-dependent relaxation of aortic segments in diabetic mice

Scientific Reports
Phuong Tran PhamMasataka Sata

Abstract

Activated factor X (FXa) plays a central role in the coagulation cascade, while it also mediates vascular function through activation of protease-activated receptors (PARs). Here, we examined whether inhibition of FXa by rivaroxaban, a direct FXa inhibitor, attenuates endothelial dysfunction in streptozotocin (STZ)-induced diabetic mice. Induction of diabetes increased the expression of a major FXa receptor, PAR2, in the aorta (P < 0.05). Administration of rivaroxaban (10 mg/kg/day) to diabetic wild-type (WT) mice for 3 weeks attenuated endothelial dysfunction as determined by acetylcholine-dependent vasodilation compared with the control (P < 0.001), without alteration of blood glucose level. Rivaroxaban promoted eNOSSer1177 phosphorylation in the aorta (P < 0.001). Induction of diabetes to PAR2-deficient (PAR2-/-) mice did not affect endothelial function and eNOSSer1177 phosphorylation in the aorta compared with non-diabetic PAR2-/- mice. FXa or a PAR2 agonist significantly impaired endothelial function in aortic rings obtained from WT mice, but not in those from PAR2-/- mice. FXa promoted JNK phosphorylation (P < 0.01) and reduced eNOSSer1177 phosphorylation (P < 0.05) in human coronary artery endothelial cells (HCAEC). FXa-...Continue Reading

References

May 11, 2000·Proceedings of the National Academy of Sciences of the United States of America·E CamererS R Coughlin
Jul 6, 2000·British Journal of Pharmacology·A S De VrieseP M Vanhoutte
Feb 13, 2001·Endocrine Reviews·J Calles-Escandon, M Cipolla
Apr 5, 2003·Arteriosclerosis, Thrombosis, and Vascular Biology·Christopher D MajorPatricia Andrade-Gordon
Aug 28, 2003·Journal of Thrombosis and Haemostasis : JTH·E B BachliJ H McVey
Nov 14, 2003·Cardiovascular Research·Carla CicalaGiuseppe Cirino
Jan 23, 2004·The Journal of Biological Chemistry·Tadamichi ShimizuHiroshi Shimizu
Apr 21, 2004·Nature Medicine·Mattias BeltingWolfram Ruf
Aug 26, 2004·American Journal of Physiology. Renal Physiology·Xuemei WangRodger Loutzenhiser
Sep 6, 2005·Arteriosclerosis, Thrombosis, and Vascular Biology·Fiorentina RoviezzoGiuseppe Cirino
Dec 20, 2005·Journal of Thrombosis and Haemostasis : JTH·C FeistritzerM Riewald
Sep 6, 2006·Circulation·Andrew J LegerAthan Kuliopulos
Sep 9, 2008·Trends in Molecular Medicine·Keren BorensztajnC Arnold Spek
Feb 6, 2009·Circulation Journal : Official Journal of the Japanese Circulation Society·Yukihito HigashiYasuki Kihara
Oct 26, 2010·Basic Research in Cardiology·Yoonjung ParkCuihua Zhang
May 6, 2011·Diabetes Care·Angelo AvogaroGian Paolo Fadini
May 6, 2011·The New England Journal of Medicine·Julian Ilcheff BorissoffHugo ten Cate
Jun 2, 2011·Biological & Pharmaceutical Bulletin·Ayaka SumiTakahiko Ono
Oct 6, 2011·Seminars in Immunopathology·Andrea S Rothmeier, Wolfram Ruf
Sep 11, 2012·Experimental and Molecular Pathology·Xiaotun ZhangRobert L Vessella
Jan 5, 2014·Cardiovascular Research·Henri M H SpronkHugo Ten Cate
Nov 15, 2014·Arteriosclerosis, Thrombosis, and Vascular Biology·Florian WilleckeIra J Goldberg
Nov 15, 2015·Journal of the American Society of Nephrology : JASN·Santhosh Kumar VrHans-Joachim Anders
Dec 8, 2015·Current Vascular Pharmacology·John Pernow, Christian Jung
Jan 23, 2016·Arteriosclerosis, Thrombosis, and Vascular Biology·Rosa Bretón-RomeroNaomi M Hamburg
Apr 30, 2016·Circulation Research·Jonathan H Foley, Edward M Conway
Jun 11, 2016·Arteriosclerosis, Thrombosis, and Vascular Biology·Yuji OeNobuyuki Takahashi
Jul 12, 2016·The Journal of Clinical Endocrinology and Metabolism·Matthieu RoustitAristidis Veves
Oct 19, 2016·Scientific Reports·Fumihiro SanadaRyuichi Morishita
Aug 29, 2017·The New England Journal of Medicine·John W EikelboomUNKNOWN COMPASS Investigators
Sep 25, 2017·British Journal of Clinical Pharmacology·Ezequiel ÁlvarezJosé Ramón González-Juanatey

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Citations

Jan 25, 2020·Journal of the American Heart Association·Boghuma TitanjiVincent C Marconi
Feb 23, 2021·Biological & Pharmaceutical Bulletin·Hideki ImanoTetsuya Hayashi
May 26, 2021·Clinical and Applied Thrombosis/hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis·Aleksandra Lenart-MigdalskaMaria Olszowska
Jul 22, 2021·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Masato NaritaHirofumi Tomita

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Methods Mentioned

BETA
protein assay
PCR

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