NR1H4 and Hypercholesterolemia: Regarding GM-mediated bile salt metabolism and its role in atherosclerosis, FXR-deficient mice have been shown to develop hypercholesterolaemia.76  Apoe and Fxr double-knockout mice develop larger atherosclerotic lesions than ApoE−/− mice.77 However, evidence in humans for a role of bile salt metabolism in atherosclerosis is limited.