Vascular protection by tetrahydrobiopterin: progress and therapeutic prospects.

Vascular protection by tetrahydrobiopterin: progress and therapeutic prospects.
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DOI:
10.1016/j.tips.2008.10.003
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发表时间:
2009-01
影响因子:
13.8
通讯作者:
Nath, Karl A.
Nath, Karl A.
中科院分区:
医学1区
文献类型:
--
作者:
Katusic, Zvonimir S.;d'Uscio, Livius V.;Nath, Karl A.

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四氢生物蝶呤 (BH4) 是内皮一氧化氮合酶 (eNOS) 活性所需的重要辅助因子。内皮细胞中 BH4 浓度低于最佳浓度会减少一氧化氮 (NO) 的生物合成,从而导致血管内皮功能障碍的发病机制。补充外源性 BH4 或增加内源性 BH4 量的治疗方法可以通过恢复 NO 的产生来减少或逆转内皮功能障碍。 BH4 口服制剂的改进刺激了临床试验,测试 BH4 在治疗全身性高血压、外周动脉疾病、冠状动脉疾病、肺动脉高压和镰状细胞病方面的功效。本综述讨论了将临床前研究中积累的知识转化为 BH4 治疗血管疾病的临床应用的持续进展。本综述还探讨了 BH4 在内皮功能调节中的新作用及其治疗意义。
Tetrahydrobiopterin (BH4) is an essential co-factor required for the activity of endothelial nitric oxide synthase (eNOS). Suboptimal concentrations of BH4 in the endothelium reduce the biosynthesis of nitric oxide (NO), thus contributing to the pathogenesis of vascular endothelial dysfunction. Supplementation with exogenous BH4 or therapeutic approaches that increase endogenous amounts of BH4 can reduce or reverse endothelial dysfunction by restoring production of NO. Improvements in formulations of BH4 for oral delivery have stimulated clinical trials which test the efficacy of BH4 in the treatment of systemic hypertension, peripheral arterial disease, coronary artery disease, pulmonary arterial hypertension, and sickle cell disease. This review discusses ongoing progress in the translation of knowledge, accumulated in pre-clinical studies, into the clinical application of BH4 in the treatment of vascular diseases. This review also addresses the emerging roles of BH4 in the regulation of endothelial function and their therapeutic implications.
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