Dan-Dan Chen, Lu-Yuan Chen, Ji-Biao Xie, Chang Shu, Tianlun Yang, Shenghua Zhou, Hong Yuan and Alex F. Chen Pages 3554 - 3562 ( 9 )
Tetrahydrobiopterin (BH<sub>4</sub>) is an essential cofactor of nitric oxide synthase (NOS). In the cardiovascular system, endothelial NOS (eNOS) has a major role in maintaining vascular tone and endothelial function, as well as in mediating many other vascular protective properties. Evidence from humans and animals have demonstrated that decreased BH<sub>4</sub> bioavailability, with subsequent uncoupling of eNOS, has significant effects on the pathogenesis of endothelial dysfunction, which is a hallmark of vascular injury in cardiovascular disorders, including hypertension, hyperlipidemia, and diabetes. In this review, we discuss the synthesis of BH<sub>4</sub>, its molecular mechanisms regulating eNOS coupling, the pathophysiologic roles of decreased BH<sub>4</sub> bioavailability in cardiovascular diseases, and the potential therapeutic application of BH<sub>4</sub> in clinics.
Tetrahydrobiopterin, endothelial nitric oxide synthase, endothelial function, eNOS uncoupling.
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