title: Rivaroxaban, a factor Xa inhibitor, improves neovascularization in the ischemic hindlimb of streptozotocin-induced diabetic mice.
abstract: BACKGROUND
  Factor Xa inhibitor is used for preventing venous thromboembolism (VTE) in adult patients receiving orthopedic operation. However, the role of factor Xa inhibitor, rivaroxaban, in angiogenesis is still unknown.
  
  
  RESULTS
  Streptozotocin (STZ)-induced diabetic mice with model of hind-limb ischemia, were divided into non-diabetic control, diabetic control, and low- and high-dose rivaroxaban treatment groups, in order to evaluate the effect of rivaroxaban in angiogenesis. Doppler perfusion imaging showed that blood flow recovery was significantly increased, and more capillary density occurred in the rivaroxaban treatment group. In vitro studies, human endothelial progenitor cells (EPCs) treated with rivaroxaban had significant functional improvement in migration and senescence under hyperglycemic conditions. Rivaroxaban also increased endothelial nitric oxide synthase (eNOS) as well as vascular endothelial growth factor (VEGF) expressions in hyperglycemia-stimulated EPCs.
  
  
  CONCLUSIONS
  Rivaroxaban promoted vessel formation in diabetic mice and improved endothelial progenitor cell function under hyperglycemic conditions. These effects may be associated with enhancement of expression of eNOS and VEGF.
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.|Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Tao-Cheng
authors.initials: TC
authors.lastname: Wu
authors.affiliation: Renal Division, Department of Internal Medicine, Taoyuan Armed Forces General Hospital, Taoyuan County, Taiwan.
authors.forename: Jenq-Shyong
authors.initials: JS
authors.lastname: Chan
authors.affiliation: Division of Cardiovascular Surgery, Department of Surgery, Healthcare and Management Center, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Chiu-Yang
authors.initials: CY
authors.lastname: Lee
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.|Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan.|Division of Cardiovascular Surgery, Department of Surgery, Healthcare and Management Center, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Hsin-Bang
authors.initials: HB
authors.lastname: Leu
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.|Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Po-Hsun
authors.initials: PH
authors.lastname: Huang
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Jia-Shiong
authors.initials: JS
authors.lastname: Chen
authors.affiliation: Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan.|Department of Medical Research and Education, Taipei Veterans General Hospital, No. 201, Section 2, Shih-Pai Road, Taipei 112, Taiwan ROC.
authors.forename: Shing-Jong
authors.initials: SJ
authors.lastname: Lin
authors.affiliation: Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan. jwchen@vghtpe.gov.tw.|Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan. jwchen@vghtpe.gov.tw.|Department of Medical Research and Education, Taipei Veterans General Hospital, No. 201, Section 2, Shih-Pai Road, Taipei 112, Taiwan ROC. jwchen@vghtpe.gov.tw.|Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan. jwchen@vghtpe.gov.tw.
authors.forename: Jaw-Wen
authors.initials: JW
authors.lastname: Chen
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004195:Disease Models, Animal; D066026:Endothelial Progenitor Cells / Q000187:drug effects* / Q000378:metabolism; D065427:Factor Xa Inhibitors / Q000494:pharmacology*; D005263:Femoral Artery / Q000601:surgery; D006614:Hindlimb / Q000098:blood supply / Q000000981:diagnostic imaging / Q000187:drug effects*; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism*; D008026:Ligation; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects / Q000378:metabolism; D000069552:Rivaroxaban / Q000494:pharmacology*; D014463:Ultrasonography; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects / Q000378:metabolism
chemical_list: D065427:Factor Xa Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000069552:Rivaroxaban; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III