Ring finger protein 10 is atherosclerosis protective and modulates macrophage polarization

Macrophages can develop into pro-inflammatory M1-like macrophages and anti-inflammatory M2-like macrophages when stimulated by distinct internal environment. Dynamic changes of the two kinds of macrophages play key roles in atherosclerosis progression. The study aims to explore the role of ring finger protein 10 (RNF10) in regulating macrophage polarization during atherosclerosis. Mice with macrophage-specific depletion of RNF10 (RNF10^Mac-KO/ApoE^-/-) and control mice (RNF10^fl/fl/ApoE^-/-) mice were fed with high-fat diet to generate atherosclerotic lesion, from which peritoneal macrophages were isolated and transfected with RNF10-overexpressing vector. Murine macrophages, RAW264.7, were transfected with RNF10-overexpressing vector or RNF10 siRNA and stimulated with oxidized low-density lipoprotein (ox-LDL) to induce foam cell formation. The RNF10^Mac-KO/ApoE^-/- mice showed greater atherosclerotic lesions, more resident macrophages, higher expression of iNOS (M1-like macrophage marker), and lower expression of Arginase-1 (M2-like macrophage marker) than the RNF10^fl/fl/ApoE^-/- mice. RNF10 overexpression could reduce expressions of IL-1β, IL-6, and iNOS (M1 marker genes), increase expressions of IL-10 and Arg-1 (M2 marker genes) in the peritoneal macrophages isolated from RNF10^Mac-KO/ApoE^-/- mice. RNF10 overexpression reduced lipid accumulation in ox-LDL-induced foam cells, whereas RNF10 silencing yielded opposite results. Our data suggest that RNF10 is associated with M1-like macrophage suppression and M2-like increase, indicating RNF10 in macrophages has an anti-atherosclerotic role.