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 (BH4) 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 BH4 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 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.
Tetrahydrobiopterin, endothelial nitric oxide synthase, endothelial function, eNOS uncoupling.
Third Xiangya Hospital, Central South University, 138 Tong Zi Bo Road, Changsha, Hunan 410013, China.