Journal
CURRENT PHARMACEUTICAL DESIGN
Volume 20, Issue 22, Pages 3554-3562Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/13816128113196660747
Keywords
Tetrahydrobiopterin; endothelial nitric oxide synthase; endothelial function; eNOS uncoupling
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Funding
- National Basic Research Program (973 Program) [2014CB542400]
- National Science Foundation of China (NSFC) [81130004, 81370359, 913392019]
- American Heart Association (AHA) [0720114Z]
- NSFC [30900519, 81370429]
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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.
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