title: Rivaroxaban, a factor Xa inhibitor, induces the secondary prevention of cardiovascular events after myocardial ischemia reperfusion injury in mice.
abstract: OBJECTIVE
  Rivaroxaban has been shown to reduce overall death from cardiovascular causes in patients with recent acute coronary syndrome. Therefore, we evaluated the secondary prevention of cardiovascular events after myocardial ischemia reperfusion injury and its mechanisms in mice.
  
  
  METHODS
  After myocardial reperfusion injury, C57BL/6J mice were randomized to receive either no treatment or treatment for 14days with low and high doses of rivaroxaban. After 7days, mice were administered tissue factor as a secondary event.
  
  
  RESULTS
  Based on a Kaplan-Meier curve analysis, the high-dose rivaroxaban group showed a significantly higher % survival than the no-treatment group from day 7 (after the administration of tissue factor) to day 14 (at the end of the experimental period). Left ventricular (LV) ejection fraction in both the low- and high-dose rivaroxaban groups improved compared to that in the no-treatment group. Moreover, mRNA levels of interleukin-6 and collagens 1α2 and 3α1 in the LV in the high-dose group were significantly suppressed compared to those in the no-treatment group.
  
  
  CONCLUSIONS
  Rivaroxaban improved the survival rate, probably by improving cardiac function through the reduction of inflammatory and fibrotic factors in the LV. This effect may be due to the pleiotropic effects of rivaroxaban beyond its main effect as an anti-coagulant.
authors.affiliation: Department of Cardiology, Fukuoka University School of Medicine, Fukuoka 814-1080, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Goto
authors.affiliation: Department of Cardiology, Fukuoka University School of Medicine, Fukuoka 814-1080, Japan; Department of Molecular Cardiovascular Therapeutics, Fukuoka University School of Medicine, Fukuoka 814-1080, Japan. Electronic address: miuras@cis.fukuoka-u.ac.jp.
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Miura
authors.affiliation: Department of Cardiology, Fukuoka University School of Medicine, Fukuoka 814-1080, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Suematsu
authors.affiliation: Department of Cardiology, Fukuoka University School of Medicine, Fukuoka 814-1080, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Idemoto
authors.affiliation: Department of Cardiology, Fukuoka University School of Medicine, Fukuoka 814-1080, Japan.
authors.forename: Kouhei
authors.initials: K
authors.lastname: Takata
authors.affiliation: Department of Cardiology, Fukuoka University School of Medicine, Fukuoka 814-1080, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Imaizumi
authors.affiliation: Department of Cardiology, Fukuoka University School of Medicine, Fukuoka 814-1080, Japan; Department of Molecular Cardiovascular Therapeutics, Fukuoka University School of Medicine, Fukuoka 814-1080, Japan.
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Uehara
authors.affiliation: Department of Cardiology, Fukuoka University School of Medicine, Fukuoka 814-1080, Japan; Department of Molecular Cardiovascular Therapeutics, Fukuoka University School of Medicine, Fukuoka 814-1080, Japan.
authors.forename: Keijiro
authors.initials: K
authors.lastname: Saku
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000473:pathology / Q000517:prevention & control; D065427:Factor Xa Inhibitors / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D011897:Random Allocation; D000069552:Rivaroxaban / Q000627:therapeutic use*; D055502:Secondary Prevention / Q000379:methods*
chemical_list: D065427:Factor Xa Inhibitors; D000069552:Rivaroxaban
keywords: Collagens 1α2 and 3α1; Interleukin-6; Myocardial ischemia reperfusion injury; Rivaroxaban; Secondary prevention