Tetrahydrobiopterin-dependent preservation of nitric oxide-mediated endothelial function in diabetes by targeted transgenic GTP-cyclohydrolase I overexpression.

Journal article

Increased production of reactive oxygen species and loss of endothelial NO bioactivity are key features of vascular disease states such as diabetes mellitus. Tetrahydrobiopterin (BH4) is a required cofactor for eNOS activity; pharmacologic studies suggest that BH4 may mediate some of the adverse effects of diabetes on eNOS function. We have now investigated the importance and mechanisms of BH4 availability in vivo using a novel transgenic mouse model with endothelial-targeted overexpression o...

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Authors: Alp, N; Mussa, S; Khoo, J; Cai, S; Guzik, T

• Publication status: Published
• Journal: Journal of clinical investigation
• Volume: 112
• Issue: 5
• Pages: 725-735
• Publication date: 2003-09-01
• DOI: 10.1172/jci17786
• EISSN: 1558-8238
• ISSN: 0021-9738
• Language: English
• Keywords: Mice, Inbred CBA; Endothelium, Vascular; Diabetes Mellitus, Experimental; Oxidative Stress; GTP Cyclohydrolase; Biopterin; Animals; Nitric Oxide Synthase Type III; Nitric Oxide; Mice; Mice, Inbred C57BL; Nitric Oxide Synthase; RNA, Messenger; Nitric Oxide Synthase Type II; Streptozocin; Superoxides