The high levels of serum total and HDL cholesterol in FXR-KO mice may at least be partially due to reduction of Sr-bi expression. Our results also found that HFD induced hepatic Sr-bi expression and this induction was, at least partially, by increasing FXR binding to multiple IR1s in the first intron of the Sr-bi gene. Thus, the accumulation of HDL cholesterol in the circulation of FXR-KO mice was at least partially due to the loss of FXR regulation of Sr-bi expression. These combined findings further established that FXR is a physiological modulator of SR-BI which may enhance HDL reverse cholesterol transport. Thus, induction of SR-BI by activation of FXR may help prevent atherosclerosis. These findings, together with the recent finding that FXR agonists Isoetharine Mesylate protect against atherosclerosis, suggest that FXR is a potential therapeutic target for maintaining cholesterol homeostasis as well as for Dimetridazole treatment of hypercholesterolemia and coronary heart disease. In summary, the current study identified Sr-bi/SR-BI as a FXR target gene in both mouse and human livers. The molecular mechanism of FXR regulation of Sr-bi gene expression is via direct binding of FXR to multiple novel FXRREs in the first intron of the Sr-bi gene. Increased total and HDL cholesterol in FXR KO mice may, at least partly, due to reduced Sr-bi expression. With the goal of improving transplantation outcomes, donor and recipient selection criteria are evolving. Unfortunately, the national kidney waiting list continues to grow disproportionate to the number of donor organs available for transplantation. Median waiting times for kidney transplant in the US exceed 3 years in the absence of a living donor. The increasing disparity between organ supply and demand challenges the transplantation community to maximize efforts and optimize the use of organs from all consented donors. Recent increases in graft availability from deceased donors have been a result of expansion of the donor acceptance criteria, including increasing use of older donors, donation-after-cardiac-death, and deceased donors with other characteristics that might be associated with increased risk of graft dysfunction. To counteract the escalating discrepancy between organ availability and need, OPTN initiated policy in 2002 defining and providing guidelines for the use of expanded criteria donor kidneys. However, ECD kidneys had been often associated with worse short and long term renal function, and the limited nephron reserve might result in a relative risk of graft loss when compared with kidneys from standard criteria donors. Growing acceptance and use of ECD and DCD kidneys has been tempered by data suggesting that ECD kidneys have an increased susceptibility to ischemia-reperfusion injury, leading to higher rates of primary non-function; delayed graft function and acute cellular rejection.