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

Abstract

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