Retinoic Acid Receptor Alpha (RARα) in Macrophages Protects from Diet-Induced Atherosclerosis in Mice.
Fathima N Cassim BawaRaja GopojuYanyong XuShuwei HuYingdong ZhuShaoru ChenKavita JadhavYanqiao ZhangPublished in: Cells (2022)
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 Rarα -/- ( Rarα Mac-/- ) mice showed increased lipid accumulation and inflammation and reduced cholesterol efflux compared to Rarα 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 Rarα Mac-/- mice and Rarα fl/fl mice. In Ldlr -/- mice, myeloid ablation of RARα significantly reduced macrophage Abca1 and Abcg1 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.
Keyphrases
- high fat diet induced
- cardiovascular disease
- oxidative stress
- adipose tissue
- poor prognosis
- low density lipoprotein
- bone marrow
- binding protein
- signaling pathway
- wild type
- insulin resistance
- metabolic syndrome
- gene expression
- immune response
- endothelial cells
- genome wide identification
- high speed
- radiofrequency ablation