Consistently, deletion or inhibition of ACAT1 in macrophages has an inhibitory effect on atherosclerosis in mouse models.96–99 However, the ACAT1 inhibitors failed to produce desired athero-protective effects in clinic, which may be due to excessive accumulation of FC in cells and generation of lipotoxicity, resulting in profound cell death.100–102 Macrophages are not able to degrade sterols, thus, CE needs to be hydrolyzed into FC for efflux. This evidence concerns the gene ACAT1 and atherosclerosis.