Heart failure is the leading cause of death worldwide. Compound Danshen Dripping Pill (CDDP) or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China. However, the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown. We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E (ApoE) and LDL receptor (LDLR) dual deficient (ApoE^–/–LDLR^–/–) mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure. CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis. Mechanistically, both Wnt and lysine-specific demethylase 4A (KDM4A) pathways were significantly activated in mice with heart injury. Conversely, CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors. While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity. In addition, CDDP attenuated simvastatin-induced myolysis in skeletal muscle. Taken together, our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.

心力衰竭是全世界死亡的主要原因。复方丹参滴丸（CDDP）或CDDP联合辛伐他汀在我国已广泛用于治疗心肌梗死等心血管疾病患者。然而，CDDP 对高胆固醇血症/动脉粥样硬化引起的心力衰竭的影响尚不清楚。我们构建了载脂蛋白 E (ApoE) 和低密度脂蛋白受体 (LDLR) 双缺陷 (ApoE –/– ^LDLR – ^{/–)高胆固醇血症/动脉粥样硬化诱导的心力衰竭新模型}) 小鼠并研究了 CDDP 或 CDDP 加低剂量辛伐他汀对心力衰竭的影响。CDDP或CDDP加低剂量辛伐他汀通过多种作用抑制心脏损伤，包括抗心肌功能障碍和抗纤维化。从机制上讲，Wnt 和赖氨酸特异性脱甲基酶 4A (KDM4A) 通路在心脏损伤小鼠中均被显着激活。相反，CDDP 或 CDDP 加上低剂量的辛伐他汀通过显着上调 Wnt 抑制剂的表达来抑制 Wnt 通路。而CDDP的抗炎和抗氧化应激作用是通过抑制KDM4A的表达和活性来实现的。此外，CDDP 减弱了辛伐他汀诱导的骨骼肌肌溶解。综合起来，