title: Reduced adenosine receptor stimulation as a pathogenic factor in hyperhomocysteinemia.
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.
authors.affiliation: Department of Pharmacology-Toxicology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. n.riksen@aig.umcn.nl
authors.forename: Niels P
authors.initials: NP
authors.lastname: Riksen
authors.forename: Gerard A
authors.initials: GA
authors.lastname: Rongen
authors.forename: Henk J
authors.initials: HJ
authors.lastname: Blom
authors.forename: Godfried H J
authors.initials: GH
authors.lastname: Boers
authors.forename: Paul
authors.initials: P
authors.lastname: Smits
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000818:Animals; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D020138:Hyperhomocysteinemia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D018047:Receptors, Purinergic P1 / Q000378:metabolism*
chemical_list: D018047:Receptors, Purinergic P1; D006710:Homocysteine; D000241:Adenosine