Potential role for adenosine in the pathogenesis of the vascular complications of hyperhomocysteinemia.
Hyperhomocysteinemia is an independent risk factor for cardiovascular disease. Most previous investigations focused on the role of homocysteine as direct pathogenetic factor for these adverse vascular events. However, the exact pathophysiological mechanism is still unknown. In this review we discuss the hypothesis that a decreased extracellular concentration of adenosine could contribute to the adverse cardiovascular effects of hyperhomocysteinemia. Fundamental to this hypothesis is that, in vivo, any increase in the plasma concentration of homocysteine reflects an increased intracellular homocysteine concentration, which inevitably will result in a decrease in the adenosine concentration. In this situation, the hydrolase reaction catalysed by S-adenosylhomocysteine hydrolase will reverse and S-adenosylhomocysteine will accumulate at the expense of adenosine. Stimulation of adenosine receptors by adenosine results in various cardio- and vasoprotective actions, like modulation of vascular resistance, presynaptic inhibition of norepinephrine release, ischaemic preconditioning, inhibition of platelet aggregation, modulation of inflammation and regulation of vascular cell proliferation and death. In this respect, a decrease in the adenosine concentration could contribute significantly to the cardiovascular effects of hyperhomocysteinemia.
Riksen
Niels P
NP
Department of Pharmacology-Toxicology, University Medical Centre Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Rongen
Gerard A
GA
Blom
Henk J
HJ
Russel
Frans G M
FG
Boers
Godfried H J
GH
Smits
Paul
P
D000241:Adenosine / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000150:complications* / Q000378:metabolism; D006706:Homeostasis; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications* / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D012435:S-Adenosylhomocysteine / Q000378:metabolism
D018047:Receptors, Purinergic P1; D006710:Homocysteine; D012435:S-Adenosylhomocysteine; D000241:Adenosine