Figure 7.

The diagram illustrates the mechanisms by which CDDP protects ApoE^–/–LDLR^–/– mice against hypercholesterolemia/atherosclerosis-induced heart failure. The long-term high-fat diet feeding induces hypercholesterolemia and atherosclerosis in ApoE^–/–LDLR^–/– mice, which results in activation of KDM4A. The activated KDM4A in cardiomyocytes induces inflammation and oxidative stress to facilitate heart injury. However, treatment of the mice with CDDP may potently reduce KDM4A expression and activity. Combined inhibition on Wnt pathway, CDDP effectively ameliorates heart failure.