Are either or both hyperuricemia and xanthine oxidase directly toxic to the vasculature? A critical appraisal.
Are either or both hyperuricemia and xanthine oxidase directly toxic to the vasculature? A critical appraisal.
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DOI：
10.1002/art.33369
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发表时间：
2012-02
影响因子：
--
通讯作者：
Terkeltaub, Robert A.
中科院分区：
文献类型：
--
作者：
Neogi, Tuhina;George, Jacob;Rekhraj, Sushma;Struthers, Allan D.;Choi, Hyon;Terkeltaub, Robert A.
基础研究和临床研究表明，高尿酸血症和黄嘌呤氧化还原酶（XOR）（产生尿酸（UA）的酶）不仅在痛风中发挥作用，而且在血管疾病中也发挥作用。目前，无症状高尿酸血症（即，在没有痛风、尿酸盐肾结石或肿瘤溶解综合征的情况下）不是治疗的适应症。随着过去几十年痛风和高尿酸血症患病率的上升，阐明高尿酸血症的潜在不良反应（在有和没有痛风的患者中）具有公共卫生重要性。UA不仅是人类嘌呤代谢的惰性终产物，而且具有潜在的抗氧化剂，促氧化剂和促炎作用。然而，对于这些效应中哪些（如果有的话）与痛风和无症状高尿酸血症中人类血管疾病的发展和并发症具有临床相关性，仍存在争议。显然，并非所有高尿酸血症患者都会发生痛风，迄今为止的研究也无法阐明哪些受试者的高尿酸血症可能对血管系统产生有害影响。此外，XOR抑制剂或促尿酸排泄剂的降尿酸治疗研究尚不能明确确定是否有任何此类效应可能由UA与XO介导。足够持续时间的大规模前瞻性随机临床试验，并采用适当的生物标志物，现在似乎对解决UA和XO在人体动脉循环中的假定毒性作用至关重要。
Basic research and clinical studies have implicated a role for hyperuricemia and for xanthine oxidoreductase (XOR), the enzyme that generates uric acid (UA), in not only gout but also vascular diseases. At present, asymptomatic hyperuricemia (i.e., in the absence of gout, urate nephrolithiasis, or tumor lysis syndrome) is not an indication for therapy. With the rise over the past several decades in prevalence of both gout and hyperuricemia, clarifying the potential adverse effects of hyperuricemia (in patients with and without gout) is of public health importance. UA is not simply an inert end-product of purine metabolism in humans, but rather has potential antioxidant, pro-oxidant, and pro-inflammatory effects. However controversy remains as to which, if any, of these effects are of clinical relevance in development and complications of human vascular diseases in gout and asymptomatic hyperuricemia. Clearly, not all individuals with hyperuricemia develop gout, and studies to date have also been unable to clarify in which subjects hyperuricemia may have detrimental effects on the vasculature. Further, studies of urate-lowering therapy with XOR inhibition or uricosuric agents have not been able to definitively identify whether any such effects may be mediated by UA versus XO. Adequately sized, prospective randomized clinical trials of sufficient duration, and employing appropriate biomarkers, now appear critical to resolve the putative toxic roles of UA and XO in the human arterial circulation.
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DOI：
10.1073/pnas.78.11.6858
发表时间：
1981-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
AMES, BN;CATHCART, R;HOCHSTEIN, P
通讯作者：
HOCHSTEIN, P
影响因子：
2.2
作者：
Conta, A. C.;Stelzner, D. J.
通讯作者：
Stelzner, D. J.
影响因子：
4.9
作者：
Corry, Dalila B.;Eslami, Pirooz;Tuck, Michael L.
通讯作者：
Tuck, Michael L.
影响因子：
18.2
作者：
Cleland, John G. F.;Coletta, Alison P.;Clark, Andrew L.
通讯作者：
Clark, Andrew L.
影响因子：
37.8
作者：
Farquharson, CA;Butler, R;Struthers, AD
通讯作者：
Struthers, AD