Eukaryotic initiation factor 6 repression mitigates atherosclerosis progression by inhibiting macrophages expressing Fasn.

Atherosclerosis, a chronic inflammatory disease that often leads to myocardial infarction and stroke, is mainly caused by lipid accumulation. Eukaryotic initiation factor 6 (Eif6) is a rate-limiting factor in protein translation of transcription factors necessary for lipogenesis. To determine whether Eif6 affects atherosclerosis, Eif6+/- mice were crossed into Apoe-/- background. Apoe-/-/Eif6+/- mice on high fat diet showed significant reduction in atherosclerotic lesions and necrotic core content in aortic root sections in comparison with Apoe-/- mice. RNA-Seq was used to investigate the effect of Eif6 in aorta. Deficiency of Eif6 shows broad effect on cell metabolism. Expression of genes for fatty acid synthesis including Fatty acid synthase (Fasn), Elovl3, Elovl6 and Acaca are down-regulated in aortas. Importantly, Fasn is decreased in macrophages. Results suggest that Eif6 deficiency may decrease atherosclerosis through inhibition of Fasn and lipids metabolism in macrophages.