title: Relationships among hyperuricemia, endothelial dysfunction and cardiovascular disease: molecular mechanisms and clinical implications.
abstract: Uric acid is the end product of purine metabolism. Its immediate precursor, xanthine, is converted to uric acid by an enzymatic reaction involving xanthine oxidoreductase. Uric acid has been formerly considered a major antioxidant in human plasma with possible beneficial anti-atherosclerotic effects. In contrast, studies in the past two decades have reported associations between elevated serum uric acid levels and cardiovascular events, suggesting a potential role for uric acid as a risk factor for atherosclerosis and related diseases. In this paper, the molecular pattern of uric acid formation, its possible deleterious effects, as well as the involvement of xanthine oxidoreductase in reactive oxygen species generation are critically discussed. Reactive oxygen species contribute to vascular oxidative stress and endothelial dysfunction, which are associated with the risk of atherosclerosis. Recent studies have renewed attention to the xanthine oxidoreductase system, since xanthine oxidoreductase inhibitors, such as allopurinol and oxypurinol, would be capable of preventing atherosclerosis progression by reducing endothelial dysfunction. Also, beneficial effects could be obtained in patients with congestive heart failure. The simultaneous reduction in uric acid levels might contribute to these effects, or be a mere epiphenomenon of the drug action. The molecular mechanisms involved are discussed.
authors.affiliation: Department of Internal Medicine, Aging and Nephrological Diseases, University of Bologna and S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Puddu
authors.forename: Giovanni M
authors.initials: GM
authors.lastname: Puddu
authors.forename: Eleonora
authors.initials: E
authors.lastname: Cravero
authors.forename: Luca
authors.initials: L
authors.lastname: Vizioli
authors.forename: Antonio
authors.initials: A
authors.lastname: Muscari
mesh_terms: D000493:Allopurinol / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants; D050197:Atherosclerosis / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000209:etiology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006801:Humans; D033461:Hyperuricemia / Q000150:complications*; D058990:Molecular Targeted Therapy; D018384:Oxidative Stress; D010117:Oxypurinol / Q000494:pharmacology / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism; D012307:Risk Factors; D014527:Uric Acid / Q000009:adverse effects* / Q000378:metabolism; D014968:Xanthine Dehydrogenase / Q000037:antagonists & inhibitors* / Q000502:physiology*
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D014527:Uric Acid; D000493:Allopurinol; D014968:Xanthine Dehydrogenase; D010117:Oxypurinol