In this review, we discuss the synthesis of BH4, its molecular mechanisms regulating eNOS coupling, the pathophysiologic roles of decreased BH4 bioavailability in cardiovascular diseases, and the potential therapeutic application of BH4 in clinics.

对的bh4不足，会因辅因子与酶的比例失衡而导致enos 脱偶联[9]。所以保持enos与bh 4的比例平衡对于脱偶联 很重要，有研究表明降低bh4水平可激活核转录因子-e2-相关因子，降低人内皮细胞enos蛋白水平，故保持 enos与bh4的比例平衡，使enos处于偶联状态，因而

2023年3月9日 · 血管 NO 由内皮一氧化氮合酶 (eNOS) 从底物 L-精氨酸 (L-Arg) 合成，四氢生物蝶呤 (BH4) 作为必需的辅助因子。 糖尿病、血脂异常、高血压、衰老或吸烟等心血管危险因素会增加血管氧化应激，从而强烈影响 eNOS 活性并导致 eNOS 解偶联。

2019年11月8日 · bh4是调节enos活性的必需辅助因子，bh4稳定enos的二聚体，促进电子转移，并使no生成与超氧化物的产生达到平衡。近来研究显示bh4与肺动脉高压有关[28]。bh4含量低与肺动脉和全身血压升高有关，补充bh4可以促进血管舒张、降低全身血压[29]。

eNOS-BH4 Interaction Stoichiometry—The stably transfected doxycycline-responsive GCH/eNOS cells enable manipulation of the intracellular eNOS:BH4 ratio and, hence, alteration of the BH4 saturation state of eNOS protein. We compared cell lines with four different eNOS:BH4 ratios, as shown in Table 1.

Recent studies have implicated BH4 recycling in the direct regulation of eNOS uncoupling, showing that inhibition of BH4 recycling using DHFR-specific siRNA and methotrexate treatment leads to eNOS uncoupling in endothelial cells and the hph-1 mouse model of BH4 deficiency, even in the absence of oxidative stress.

2009年1月9日 · Tetrahydrobiopterin (BH4) is a critical determinant of endothelial nitric-oxide synthase (eNOS) activity. In the absence of BH4, eNOS becomes "uncoupled" and generates superoxide rather than NO.

2017年1月1日 · Results: Sepiapterin effectively enhanced BH4 levels in hyperoxia-exposed retinas and brains, elevated NOS activity, and reduced NT-modified protein, leading to reversal of the exacerbated vasoregression observed in the presence of eNOS overexpression.

Tetrahydrobiopterin (BH4) functions as a cofactor for several important enzyme systems, and considerable evidence implicates BH4 as a key regulator of endothelial nitric oxide synthase (eNOS) in the setting of cardiovascular health and disease.

2003年12月4日 · In this article, we review the current knowledge on the regulation of eNOS by BH4 and discuss the potential importance of mechanisms linking BH4 availability with endothelial function in vascular disease.