Nitric oxide (NO) produced by endothelial nitric
oxide synthase (eNOS) is a key mediator of vascular
homeostasis. eNOS enzymatic activity appears to be
determined by the availability of its cofactor
tetrahydrobiopterin (BH4). BH4 bioavailability is
limited by oxidative degradation in dysfunctional
endothelium, and by alterations in the rate of its
biosynthesis, governed by the rate-limiting enzyme
GTP cyclohydrolase 1 (GTPCH). In this project novel
targeted transgenic mouse lines were generated with
endothelial-specific over-expression of human GTPCH.
These studies have shown that BH4...