title: Nucleoside Transport Inhibition by Dipyridamole Prevents Angiogenesis Impairment by Homocysteine and Adenosine.
abstract: OBJECTIVE
  Adenosine plays an important role in the pathogenesis of homocysteine-associated vascular complications.
  
  
  METHODS
  This study examined the effects of dipyridamole, an inhibitor for nucleoside transport, on impaired angiogenic processes caused by homocysteine and adenosine in human cardiovascular endothelial cell line (EAhy926).
  
  
  RESULTS
  The results showed that dipyridamole restored the extracellular adenosine and intracellular S-adenosylhomocysteine concentrations disrupted by the combination of homocysteine and adenosine. Dipyridamole also ameliorated the impaired proliferation, migration and formation of capillary-like tubes of EAhy926 cells caused by the combination of homocysteine and adenosine. Mechanism analysis revealed that dipyridamole induced the phosphorylation of mitogen-activated protein kinase kinase (MEK) and extracellular signal-regulated kinases (ERK) and its effect on cell growth was attenuated by the MEK inhibitor, U0126.
  
  
  CONCLUSIONS
  Dipyridamole protected against impaired angiogenesis caused by homocysteine and adenosine, at least in part, by activating the MEK/ERK signalling pathway, and this could be associated with its effects in suppressing intracellular S-adenosylhomocysteine accumulation.
  This is the first paper showing that nucleoside transport inhibition by dipyridamole reduced impaired angiogenic process caused by homocysteine and adenosine.
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore Faculty of Pharmacy, the University of Sydney; National Institute of Complementary Medicine (NICM), Western Sydney University, NSW, Australia; School of Biological Sciences, Nanyang Technological University, Singapore.
authors.forename: Antony
authors.initials: A
authors.lastname: Kam
authors.forename: Valentina
authors.initials: V
authors.lastname: Razmovski-Naumovski
authors.forename: Xian
authors.initials: X
authors.lastname: Zhou
authors.forename: John
authors.initials: J
authors.lastname: Troung
authors.forename: Kelvin
authors.initials: K
authors.lastname: Chan
mesh_terms: D000241:Adenosine; D001693:Biological Transport, Active / Q000187:drug effects; D002196:Capillaries / Q000187:drug effects / Q000254:growth & development; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004176:Dipyridamole / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006710:Homocysteine; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000517:prevention & control*; D009705:Nucleosides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D009705:Nucleosides; D014665:Vasodilator Agents; D006710:Homocysteine; D004176:Dipyridamole; D012435:S-Adenosylhomocysteine; D000241:Adenosine