Tetrahydrobiopterin Concentrations in Normal and Coronary Artery Diseased Heart Tissue

Tetrahydrobiopterin (BH4) is an essential cofactor that controls the enzymatic activity of aromatic amino acid hydroxylases as well as all forms of nitric oxide synthase (NOS), which include endothelial (eNOS), neuronal (nNOS) and inducible (iNOS) isoforms [1]. In coronary arteries, reduced availability of BH4 in the endothelium causes decreased production of nitric oxide and an increase in eNOSderived production of reactive oxygen species including superoxide anion and hydrogen peroxide [2,3]. Studies have demonstrated that oxidative stress causes uncoupling of eNOS and endothelial dysfunction, which is associated with chemical inactivation of BH4 and its oxidation to dihydrobiopterin (BH2) [4]. There is mounting evidence that this mechanism plays a particularly important role in coronary artery disease (CAD). For instance, low BH4 and BH4/BH2 ratio have been found to be decreased in plasma of patients with CAD and in blood vessel wall [5]. BH4 levels are reported to be reduced in heart tissue from rodent models of cardiac ischemia that results in NOS decoupling [6-8].