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Reduced adenosine receptor stimulation as a pathogenic factor in hyperhomocysteinemia

  • Niels P. Riksen , Gerard A. Rongen , Henk J. Blom , Godfried H. J. Boers and Paul Smits
Published/Copyright: September 30, 2005

Abstract

In this review we discuss the hypothesis, and current evidence, that a decreased concentration of the endogenous purine-nucleoside adenosine contributes to the increased cardiovascular risk of patients with hyperhomocysteinemia. In hyperhomocysteinemia, the reaction equilibrium of the reaction catalysed by S-adenosylhomocysteine hydrolase will shift towards synthesis of S-adenosylhomocysteine, at the expense of free adenosine. Adenosine receptor stimulation induces several cardiovascular protective effects, such as vasodilation, inhibition of thrombocyte aggregation, of inflammation and of vascular smooth muscle cell proliferation. A decreased adenosine concentration could, therefore, well contribute to the cardiovascular complications of hyperhomocysteinemia. Previous animal studies have shown that administration of homocysteine decreases extracellular adenosine, associated with increased synthesis of S-adenosylhomocysteine. Recently, we showed that in patients with classical homocystinuria, cellular adenosine uptake is enhanced, thus limiting adenosine-induced vasodilation. These observations provide us with additional pharmacological targets, such as adenosine uptake inhibition, to reduce cardiovascular risk in patients with hyperhomocysteinemia.


Corresponding author: Niels P. Riksen, MD, Department of Pharmacology-Toxicology 233, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands Phone: +31-24-361-3691, Fax: +31-24-361-4214,

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Published Online: 2005-9-30
Published in Print: 2005-10-1

©2005 by Walter de Gruyter Berlin New York

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