Department of Internal Medicine, Aging and Nephrological Diseases, University of Bologna and S. Orsola-Malpighi Hospital, Bologna, Italy.
J Cardiol. 2012 May;59(3):235-42. doi: 10.1016/j.jjcc.2012.01.013. Epub 2012 Mar 6.
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.
尿酸是嘌呤代谢的终产物。其直接前体黄嘌呤通过涉及黄嘌呤氧化还原酶的酶促反应转化为尿酸。尿酸曾被认为是人类血浆中的一种主要抗氧化剂，具有潜在的抗动脉粥样硬化作用。相比之下，过去二十年的研究报告了血清尿酸水平升高与心血管事件之间的关联，表明尿酸可能是动脉粥样硬化和相关疾病的一个风险因素。在本文中，我们批判性地讨论了尿酸形成的分子模式、其可能的有害作用，以及黄嘌呤氧化还原酶在活性氧生成中的作用。活性氧会导致血管氧化应激和内皮功能障碍，这与动脉粥样硬化的风险有关。最近的研究重新引起了对黄嘌呤氧化还原酶系统的关注，因为黄嘌呤氧化还原酶抑制剂，如别嘌呤醇和氧嘌呤醇，通过减少内皮功能障碍，有可能预防动脉粥样硬化的进展。此外，在充血性心力衰竭患者中也能获得有益的效果。尿酸水平的同时降低可能有助于这些效果，或者仅仅是药物作用的一种偶然现象。本文讨论了所涉及的分子机制。
