Cardiac Allograft Remodeling and Effects of Sirolimus

Cardiac allograft remodeling causes poor quality of life, allograft failure and increased mortality after heart transplantation. Risk factors for cardiac allograft remodeling and its progression are poorly defined and there is a need for effective interventions.This is a multi-factorial phenomenon, associated with various immunological and non-immunological factors. Animal studies suggest M-TOR inhibition attenuates cardiac allograft remodeling secondary to down-regulation of M-TOR downstream targets and increased autophagy. There is a paucity of data regarding effect of Sirolimus, a M-TOR inhibitor, on human heart remodeling. This aim of the proposal to identify the prevalence of cardiac allograft remodeling on current immunosuppressive strategies and determine risk factors for its development. It will also identify molecular pathways associated with cardiac allograft remodeling and determine the impact of Sirolimus on these pathways.