GPR146 inhibition protects against atherosclerosis

GPR146 inhibition protects against atherosclerosisHuman genetic studies have established the orphan G proteincoupled receptor gene, GPR146, as a regulator of plasma cholesterol levels.In line with these findings, Yu et al. report that depletion of GPR146 in mice substantially reduces circulating LDL-cholesterol and triglyceride levels, through activation of ERK signalling and promotion of SREBP2 activity.The lipid-lowering effects of GPR146 depletion protected mice against atherosclerosis in an LDL receptor (LDLR)-independent manner, reducing lesion area by up to 90%.Injection of LDLR -/- mice with an AAV-delivered shRNA targeting GPR146 lowered plasma total cholesterol levels.