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Compound Danshen Dripping Pill inhibits hypercholesterolemia/atherosclerosis-induced heart failure in ApoE and LDLR dual deficient mice via multiple mechanisms.

ABSTRACT: 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.

SUBMITTER: Yang Y

PROVIDER: S-EPMC10031343 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Publications

Compound Danshen Dripping Pill inhibits hypercholesterolemia/atherosclerosis-induced heart failure in ApoE and LDLR dual deficient mice <i>via</i> multiple mechanisms.

Yang Yanfang Y Feng Ke K Yuan Liying L Liu Yuxin Y Zhang Mengying M Guo Kaimin K Yin Zequn Z Wang Wenjia W Zhou Shuiping S Sun He H Yan Kaijing K Yan Xijun X Wang Xuerui X Duan Yajun Y Hu Yunhui Y Han Jihong J

Acta pharmaceutica Sinica. B 20221115 3

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 (Ap ...[more]

PMID: 36970211

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Project description:BackgroundLong-term use of nitrates for treating stable angina pectoris (SAP) may lead to patients' tolerance to nitrates. As a traditional Chinese medicine, Compound danshen dropping pills (CDDP) is beneficial for patients with SAP. This study aimed to critically assess the efficacy and safety of CDDP vs. nitrates for SAP.MethodsPubMed, Embase, Web of Science, Cochrane library, CNKI, Wanfang Digital Periodicals, and Chinese Science and Technology Periodicals database were searched from inception to April 2023. Randomized controlled trials (RCTs) comparing CDDP with nitrates for SAP were included. The meta-analysis was conducted to estimate the pooled effect.ResultsTwenty-nine studies were included for the statistical analysis. The meta-analyses with the random-effect model indicated that CDDP could significantly increase the effective rate in symptom improvement compared with nitrates (Pooled 9 RCTs, OR = 1.95, 95% CI: 1.25-3.05, P = 0.003, duration of 4 weeks; Pooled 4 RCTs, OR = 3.45, 95% CI: 1.84-6.48, P = 0.0001, duration of 6 weeks; Pooled 13 RCTs, OR = 4.02, 95% CI: 2.14-7.57, P < 0.0001, duration of 8 weeks). The meta-analyses with the random-effect model indicated that CDDP could significantly increase the effective rate in electrocardiogram improvement compared with nitrates (Pooled 5 RCTs, OR = 1.60, 95% CI: 1.02-2.52, P = 0.04, duration of 4 weeks; Pooled 3 RCTs, OR = 2.47, 95% CI: 1.60-3.82, P < 0.0001, duration of 6 weeks; Pooled 11 RCTs, OR = 3.43, 95% CI: 2.68-4.38, P < 0.00001, duration of 8 weeks). The incidence of adverse drug reactions in the CDDP group was lower than that in the nitrates group (Pooled 23 RCTs, OR = 0.15, 95% CI: 0.1-0.21, P < 0.00001). The results of the meta-analyses with fixed-effect model were similar with above results. The levels of the evidence ranged from very low to low.ConclusionThe present study suggests that CDDP with the duration of at least 4 weeks can be considered as an alternative to nitrates for treating SAP. However, more high-quality RCTs are still needed to confirm these findings.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022352888, identifier [CRD42022352888].

Dataset Information

Compound Danshen Dripping Pill inhibits hypercholesterolemia/atherosclerosis-induced heart failure in ApoE and LDLR dual deficient mice via multiple mechanisms.

Publications

Compound Danshen Dripping Pill inhibits hypercholesterolemia/atherosclerosis-induced heart failure in ApoE and LDLR dual deficient mice <i>via</i> multiple mechanisms.

Similar Datasets

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