Nucleoside Transport Inhibition by Dipyridamole Prevents Angiogenesis Impairment by Homocysteine and Adenosine

Authors

  • Antony Kam 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 http://orcid.org/0000-0003-2155-6887
  • Valentina Razmovski-Naumovski Faculty of Pharmacy, University of Sydney; National Institute of Complementary Medicine (NICM), Western Sydney University; School of Medicine, University of New South Wales, NSW, Australia
  • Xian Zhou National Institute of Complementary Medicine (NICM), Western Sydney University, NSW, Australia; School of Biological Sciences, Nanyang Technological University, Singapore
  • John Troung National Institute of Complementary Medicine (NICM), Western Sydney University, NSW, Australia; School of Biological Sciences, Nanyang Technological University, Singapore
  • Kelvin Chan University of Western Sydney, NSW, Australia / Liverpool John Moores University, Merseyside, UK

DOI:

https://doi.org/10.18433/J3TG88

Abstract

Purpose: 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. Conclusion: 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.
Novelty of the Work: This is the first paper showing that nucleoside transport inhibition by dipyridamole reduced impaired angiogenic process caused by homocysteine and adenosine.

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Published

2015-12-08

How to Cite

Kam, A., Razmovski-Naumovski, V., Zhou, X., Troung, J., & Chan, K. (2015). Nucleoside Transport Inhibition by Dipyridamole Prevents Angiogenesis Impairment by Homocysteine and Adenosine. Journal of Pharmacy & Pharmaceutical Sciences, 18(5), 871–881. https://doi.org/10.18433/J3TG88

Issue

Vol. 18 No. 5 (2015)

Section

Pharmaceutical Sciences; Review Articles

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