Mechanistically, blockade of macrophagic sclerostin loop2-ApoER2 interaction attenuates the suppressive effects of sclerostin on NF-κB nuclear translocation, phosphorylation, and mRNA expression in macrophages, reduces the promotive effects of sclerostin on macrophage conversion to anti-inflammatory phenotypes, and inhibits the preventive effects of sclerostin on atherosclerosis and aortic aneurysm in ApoE<sup>-/-</sup> mice. The gene discussed is APOE; the disease is atherosclerosis.