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Qiliqiangxin Improves Cardiac Function through Regulating Energy Metabolism via HIF-1?-Dependent and Independent Mechanisms in Heart Failure Rats after Acute Myocardial Infarction.

ABSTRACT: The present study is aimed at investigating whether Qiliqiangxin (QL) could regulate myocardial energy metabolism in heart failure rats after acute myocardial infarction (AMI) and further exploring the underlying mechanisms. AMI was established by ligating the left anterior descending coronary artery in adult male SD rats. AMI rats with ejection?fraction?(EF) < 50% at two weeks after the operation were chosen as heart failure rats for the main study. Rats were randomized into the sham, MI, MI+QL, and MI+QL+2-MeOE2 groups. The results showed that compared with the MI group, QL significantly improved cardiac function, reduced serum NT-proBNP level, and alleviated myocardial fibrosis. QL also increased myocardial capillary density by upregulated protein expressions of vascular endothelial growth factor (VEGF) and CD31 by regulating the HIF-1?/VEGF pathway. Moreover, QL promoted ATP production, glucose uptake, and glycolysis by upregulating HIF-1? and a series of glycolysis-relevant enzymes in a HIF-1?-dependent manner. QL also improved myocardial glucose oxidation enzyme expression and free fatty acid uptake by a HIF-1?-independent pathway. Our results indicate that QL treatment improves cardiac function through regulating glucose uptake, FFA uptake, and key enzymes of energy metabolism via HIF-1?-dependent and independent mechanisms.

SUBMITTER: Wang Y

PROVIDER: S-EPMC7306086 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Qiliqiangxin Improves Cardiac Function through Regulating Energy Metabolism via HIF-1α-Dependent and Independent Mechanisms in Heart Failure Rats after Acute Myocardial Infarction.

Wang Yanyan Y Fu Mingqiang M Wang Jingfeng J Zhang Jingjing J Han Xueting X Song Yu Y Fan Yuyuan Y Hu Kai K Zhou Jingmin J Ge Junbo J

BioMed research international 20200612

The present study is aimed at investigating whether Qiliqiangxin (QL) could regulate myocardial energy metabolism in heart failure rats after acute myocardial infarction (AMI) and further exploring the underlying mechanisms. AMI was established by ligating the left anterior descending coronary artery in adult male SD rats. AMI rats with ejection fraction (EF) < 50% at two weeks after the operation were chosen as heart failure rats for the main study. Rats were randomized into the sham, MI ...[more]

PMID: 32626732

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Project description:Ethnopharmacological relevance: Shexiang Baoxin Pill (SBP) is a traditional formulation of a Chinese patent medicine, which has been commonly used for the treatment of cardiovascular disease (CVD) in China since the 1980s. Previous clinical studies have shown that SBP is safe and effective in patients with CVD, but the mechanism of the therapeutic effect is still poorly understood and requires further research. Aim of the study: This study aims to comprehensively understand the effects and the underlying mechanisms of SBP for CVD treatment by analyzing the whole proteome of myocardial infarction (MI) model rats with or without SBP treatment. Materials and methods: We evaluated the therapeutic effects of SBP on myocardial infarction model (MI) rats by performing the echocardiography analyses after 15-day treatment. And the label-free quantitative proteomic approach was utilized to investigate the whole proteome of the rat heart tissues from MI group (MI rats, n=3), SBP group (MI rats treated with SBP, n=3) and SOG group (sham operated rats, n=3) on the operation day (Day 0) and 15 days after operation (Day 15), respectively. The differentially expressed proteins were subsequently analyzed with bioinformatical methods such as KEGG pathway enrichment analysis, gene ontology (GO)-annotation analysis and protein-protein interaction (PPI) network analysis. Finally, the expression levels of two promising proteins were validated by immunoblotting. Results: The echocardiography analyses show SBP significantly improved the left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) of MI rats. Additionally, 134 proteins were differentially expressed both between SBP/MI and SOG/MI, and 15 proteins were found closely related to CVD. The pathway enrichment and GO-annotation analysis of these differentially expressed proteins revealed that the proteins involved in cellular mitochondrial energy metabolism processes, such as fatty acid beta-oxidation and aerobic respiration, were significantly regulated under SBP treatments, of which fatty acid-binding protein 3 (FABP3) and myoglobin (MB) was significantly down-regulated in MI model group compared with SOG group and was returned to the basal level by SBP treatment. Expression levels of these two proteins were confirmed by immunoblotting experiments. Conclusions: These results we obtained in current study probably demonstrated that the cardio-protective effects of Shexiang Baoxin Pill might be achieved through the regulation of energy metabolism homeostasis in cardiac tissue.

Dataset Information

Qiliqiangxin Improves Cardiac Function through Regulating Energy Metabolism via HIF-1?-Dependent and Independent Mechanisms in Heart Failure Rats after Acute Myocardial Infarction.

Publications

<i>Qiliqiangxin</i> Improves Cardiac Function through Regulating Energy Metabolism via HIF-1<i>α</i>-Dependent and Independent Mechanisms in Heart Failure Rats after Acute Myocardial Infarction.

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