Reduced adenosine receptor stimulation as a pathogenic factor in hyperhomocysteinemia.
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.
Riksen
Niels P
NP
Department of Pharmacology-Toxicology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. n.riksen@aig.umcn.nl
Rongen
Gerard A
GA
Blom
Henk J
HJ
Boers
Godfried H J
GH
Smits
Paul
P
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*
D018047:Receptors, Purinergic P1; D006710:Homocysteine; D000241:Adenosine