Lowering Asymmetric Dimethylarginine (ADMA) concentrations suppresses graft coronary artery disease in a murine heterotopic heart transplantation model

Abstract

Aims: Graft coronary artery disease (GCAD) is the leading cause of death after the first year of heart transplantation. A reduced bioavailability of endothelium-derived nitric oxide (NO) may play a role in the development of endothelial dysfunction and the structural changes, characteristic of GCAD. A potential contributor to endothelial pathobiology is asymmetric dimethylarginine (ADMA), an endogenous NO synthase inhibitor. We investigated whether lowering ADMA concentrations by dimethylarginine dimethylaminohydrolase (DDAH) overexpression in the recipient suppresses GCAD and long-term immune response in murine cardiac allografts.