Endothelial cell-specific roles for tetrahydrobiopterin in myocardial function, cardiac hypertrophy, and response to myocardial ischemia-reperfusion injury
Surawee Chuaiphichai, Sandy M. Chu, Ricardo Carnicer, Matthew Kelly, J K Bendall, Jillian N. Simon, Gillian Douglas, Mark J. Crabtree, Barbara Casadei, Keith M. Channon
Abstract
We demonstrate a critical role for endothelial cell Gch1/BH 4 biosynthesis in coronary vascular function and cardiac function. Loss of cardiac endothelial cell BH 4 leads to coronary vascular dysfunction, reduced functional recovery, and increased myocardial infarct size following ischemia/reperfusion injury. Targeting endothelial cell Gch1 and BH 4 biosynthesis may provide a novel therapeutic target for the prevention and treatment of cardiac dysfunction, ischemia injury, and heart failure.
Topics & Concepts
TetrahydrobiopterinCardiologyMedicineIschemiaHeart failureInternal medicineEndothelial dysfunctionReperfusion injuryCardiac function curveEndothelial stem cellNitric oxideChemistryNitric oxide synthaseBiochemistryIn vitroNitric Oxide and Endothelin EffectsMitochondrial Function and PathologyIon Transport and Channel Regulation