title: Cyanate-Impaired Angiogenesis: Association With Poor Coronary Collateral Growth in Patients With Stable Angina and Chronic Total Occlusion.
abstract: Cyanate has recently gained attention for its role in the pathogenesis of vascular injury. Nonetheless, the effect of cyanate on angiogenesis remains unclear.
  
  
  
  In this study, we demonstrated that oral administration of cyanate impaired blood perfusion recovery in a mouse hind-limb ischemia model. A reduction in blood perfusion recovery at day 21 was observed in the ischemic tissue of cyanate-treated mice. Likewise, there were fewer capillaries in the ischemic hind-limb tissue of cyanate-exposed mice. Our in vitro study showed that cyanate, together with its carbamylated products, inhibited the migration, proliferation, and tube-formation abilities of endothelial cells. Further research revealed that cyanate regulated angiogenesis partly by interrupting the vascular endothelial growth factor receptor 2/phosphatidylinositol 3-kinase/Akt pathway. The serum concentrations of homocitrulline, a marker of cyanate exposure, were determined in 117 patients with stable angina and chronic total occlusion. Consistent with the antiangiogenic role of cyanate, homocitrulline levels were increased in patients with poor coronary collateralization (n=58) compared with those with high collateralization (n=59; 21.09±13.08 versus 15.54±9.02 ng/mL, P=0.009). In addition, elevated homocitrulline concentration was a strong predictor of poor coronary collateral growth.
  
  
  
  Impaired angiogenesis induced by cyanate might contribute to poor coronary collateral growth.
authors.affiliation: Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jia Teng
authors.initials: JT
authors.lastname: Sun
authors.affiliation: Institute of Cardiovascular Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Yang
authors.affiliation: Institute of Neuroscience, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Jing Yan
authors.initials: JY
authors.lastname: Mao
authors.affiliation: Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Institute of Cardiovascular Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Wei Feng
authors.initials: WF
authors.lastname: Shen
authors.affiliation: Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
authors.affiliation: Shanghai Key Laboratory of Hypertension and Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Qi Hong
authors.initials: QH
authors.lastname: Wu
authors.affiliation: Institute of Cardiovascular Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yan Ping
authors.initials: YP
authors.lastname: Wang
authors.affiliation: Institute of Cardiovascular Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Li Ping
authors.initials: LP
authors.lastname: Wu
authors.affiliation: Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China rjzhangruiyan@126.com.
authors.forename: Rui Yan
authors.initials: RY
authors.lastname: Zhang
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000704:Analysis of Variance; D060050:Angina, Stable / Q000000981:diagnostic imaging / Q000503:physiopathology; D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D002908:Chronic Disease; D002956:Citrulline / Q000031:analogs & derivatives / Q000378:metabolism; D003097:Collateral Circulation / Q000502:physiology*; D017023:Coronary Angiography; D054059:Coronary Occlusion / Q000000981:diagnostic imaging / Q000503:physiopathology; D003485:Cyanates / Q000008:administration & dosage / Q000494:pharmacology*; D004730:Endothelium, Vascular; D005260:Female; D006614:Hindlimb / Q000098:blood supply*; D006801:Humans; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D008810:Mice, Inbred C57BL; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors
chemical_list: D043925:Angiogenesis Inducing Agents; D003485:Cyanates; C001352:homocitrulline; D002956:Citrulline; C000592875:Kdr protein, mouse; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: angiogenesis; carbamylation; chronic total coronary occlusion; collateral circulation; cyanate; endothelial dysfunction