Maastricht University Medical Centre, Cardiovascular Research Institute Maastricht, Dept. of Cardiology, Maastricht, The Netherlands.
J Mol Cell Cardiol. 2011 Oct;51(4):559-63. doi: 10.1016/j.yjmcc.2011.03.009. Epub 2011 Mar 31.
Tetrahydrobiopterin (BH(4)) is an essential cofactor for aromatic amino acid hydroxylases and for all three nitric oxide synthase (NOS) isoforms. It also has a protective role in the cell as an antioxidant and scavenger of reactive nitrogen and oxygen species. Experimental studies in humans and animals demonstrate that decreased BH(4)-bioavailability, with subsequent uncoupling of endothelial NOS (eNOS) plays an important role in the pathogenesis of endothelial dysfunction, hypertension, ischemia-reperfusion injury, and pathologic cardiac remodeling. Synthetic BH(4) is clinically approved for the treatment of phenylketonuria, and experimental studies support its capacity for ameliorating cardiovascular pathophysiologies. To date, however, the translation of these studies to human patients remains limited, and early results have been mixed. In this review, we discuss the pathophysiologic role of decreased BH(4) bioavailability, molecular mechanisms regulating its metabolism, and its potential therapeutic use as well as pitfalls as an NOS-modulating drug. This article is part of a special issue entitled ''Key Signaling Molecules in Hypertrophy and Heart Failure.''
四氢生物蝶呤（BH（4））是芳香族氨基酸羟化酶和三种一氧化氮合酶（NOS）同工酶的必需辅助因子。它在细胞中还具有抗氧化和清除活性氮和氧物种的保护作用。人类和动物的实验研究表明，BH（4）生物利用度降低，随后内皮型一氧化氮合酶（eNOS）解偶联，在血管内皮功能障碍、高血压、缺血再灌注损伤和病理性心脏重构的发病机制中发挥重要作用。合成 BH（4）已被临床批准用于治疗苯丙酮尿症，实验研究支持其改善心血管病理生理的能力。然而，到目前为止，这些研究在人类患者中的转化仍然有限，早期结果喜忧参半。在这篇综述中，我们讨论了 BH（4）生物利用度降低的病理生理作用、调节其代谢的分子机制，以及作为 NOS 调节药物的潜在治疗用途和陷阱。本文是题为“肥大和心力衰竭中的关键信号分子”的特刊的一部分。
