Physics Commons^™

Increasing Tetrahydrobiopterin In Cardiomyocytes Adversely Affects Cardiac Redox State And Mitochondrial Function Independently Of Changes In No Production, Savitha Sethumadhavan, Jennifer Whitsett, Brian Bennett, Irina A. Ionova, Galen M. Pieper, Jeannette Vasquez-Vivar

Physics Faculty Research and Publications

Tetrahydrobiopterin (BH₄) represents a potential strategy for the treatment of cardiac remodeling, fibrosis and/or diastolic dysfunction. The effects of oral treatment with BH₄ (Sapropterin™ or Kuvan™) are however dose-limiting with high dose negating functional improvements. Cardiomyocyte-specific overexpression of GTP cyclohydrolase I (mGCH) increases BH₄ several-fold in the heart. Using this model, we aimed to establish the cardiomyocyte-specific responses to high levels of BH₄. Quantification of BH₄ and BH₂ in mGCH transgenic hearts showed age-based variations in BH₄:BH₂ ratios. Hearts of mice (<6 >months) have lower BH₄:BH_{2 …}