Retinoic Acid Receptor Alpha (RARα) in Macrophages Protects from Diet-Induced Atherosclerosis in Mice

Retinoic acid signaling plays an important role in regulating lipid metabolism and inflammation. However, the role of retinoic acid receptor alpha (RAR alpha) in atherosclerosis remains to be determined. In the current study, we investigated the role of macrophage RAR alpha in the development of atherosclerosis. Macrophages isolated from myeloid-specific Rar alpha(-/-) (Rar alpha(Mac-/-)) mice showed increased lipid accumulation and inflammation and reduced cholesterol efflux compared to Rar alpha(fl/fl) (control) mice. All-trans retinoic acid (AtRA) induced ATP-binding cassette subfamily A member 1 (Abca1) and Abcg1 expression and cholesterol efflux in both Rar alpha(Mac-/-) mice and Rar alpha(fl/fl) mice. In Ldlr(-/-) mice, myeloid ablation of RAR alpha significantly reduced macrophage Abca1 and Abcg1 expression and cholesterol efflux, induced inflammatory genes, and aggravated Western diet-induced atherosclerosis. Our data demonstrate that macrophage RAR alpha protects against atherosclerosis, likely via inducing cholesterol efflux and inhibiting inflammation.