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Nucleoside transport inhibition by dipyridamole prevents angiogenesis impairment by homocysteine and adenosine

Kam, A and Razmovski-Naumovski, V and Zhou, X and Truong, J and Chan, K (2015) Nucleoside transport inhibition by dipyridamole prevents angiogenesis impairment by homocysteine and adenosine. Journal of Pharmacy and Pharmaceutical Sciences, 18 (5). pp. 871-8881. ISSN 1482-1826

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Abstract

© 2015, Canadian Society for Pharmaceutical Sciences. All rights reserved.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. © 2015, Canadian Society for Pharmaceutical Sciences. All rights reserved

Item Type: Article
Uncontrolled Keywords: 1115 Pharmacology And Pharmaceutical Sciences
Subjects: R Medicine > RS Pharmacy and materia medica
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Canadian Society for Pharmaceutical Sciences
Date Deposited: 20 Jun 2016 09:50
Last Modified: 20 Jun 2016 09:50
DOI or Identification number: 10.18433/J3TG88
URI: http://researchonline.ljmu.ac.uk/id/eprint/3796

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