Rivaroxaban, a factor Xa inhibitor, improves neovascularization in the ischemic hindlimb of streptozotocin-induced diabetic mice

Cardiovascular Diabetology

Jaw-Wen Chen¹  Shing-Jong Lin⁵  Jia-Shiong Chen⁶  Po-Hsun Huang²  Hsin-Bang Leu⁴  Chiu-Yang Lee⁴  Jenq-Shyong Chan³  Tao-Cheng Wu² 

[1] Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan;Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan;Renal Division, Department of Internal Medicine, Taoyuan Armed Forces General Hospital, Taoyuan County, Taiwan;Division of Cardiovascular Surgery, Department of Surgery, Healthcare and Management Center, Taipei Veterans General Hospital, Taipei, Taiwan;Department of Medical Research and Education, Taipei Veterans General Hospital, No. 201, Section 2, Shih-Pai Road, Taipei 112, Taiwan ROC;Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan

关键词: Endothelial progenitor cells;    Angiogenesis;    Diabetes;    Factor Xa inhibitor;   

Others  :  1216827
DOI  :  10.1186/s12933-015-0243-y

 received in 2015-03-12, accepted in 2015-06-06,  发布年份 2015

【 摘 要 】

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.

Methods and 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.

【 授权许可】

   
2015 Wu et al.

【 图 表 】

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