Mechanistically, the cardiovascular risk of Scl-abs stems from their suppression of loop2, which mediates sclerostin’s inhibitory effect on inflammatory cytokines and chemokines such as IL-6, MCP-1, TNF-α, interferon-γ, et al., in VSMCs and macrophages, thus preventing the genesis of abdominal aortic aneurysm and atherosclerosis (Fig. 4).144,145 Thus, targeting loop3 of sclerostin can partially reverse sclerostin’s bone inhibition without affecting loop2’s cardiovascular protection. The gene discussed is SOST; the disease is abdominal aortic aneurysm.