Inhibition of ABCA1 protein degradation promotes HDL cholesterol efflux capacity and RCT and reduces atherosclerosis in mice.

摘要: ABCA1 plays a key role in the initial lipidation of apoA-I, which generates circulating HDL cholesterol. Whereas it is known that transcriptional upregulation promotes formation and reverse cholesterol transport (RCT), not how inhibition protein degradation impacts function. Employing small molecule triacetyl-3-hydroxyphenyladenosine (IMM-H007), we determined attenuation affects efflux capacity, RCT, atherosclerotic lesion formation. Pulse-chase analysis revealed IMM-H007 inhibits facilitates its cell-surface localization macrophages, additional studies macrophages showed thereby efflux. treatment Paigen diet-fed mice caused an increase level, increased capacity HDL, enhanced vivo RCT from to plasma, liver, feces. Furthermore, suppression by reduced plaque apoE(-/-) mice. Thus, via effects on both ABCA1-expressing cells function, attenuates atherogenesis. potentially represents lead compound for development agents augment