Dataset Information

Quantitative proteomics uncovers the regulation of energy metabolism by Shexiang Baoxin Pill in myocardial infarction model rats

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Heart

SUBMITTER: Yue Yu

LAB HEAD: Hu Zhou

PROVIDER: PXD019296 | Pride | 2020-12-14

REPOSITORIES: Pride

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Quantitative proteomics reveals Shexiang Baoxin Pill exerts cardioprotective effects by preserving energy metabolism in a rat model of myocardial infarction.

Yu Feng F Yu Yue Y Tian Saisai S Zhou Yanting Y Chen Xiangling X Ye Ji J Liu Qian Q Xu Xike X Zhou Hu H Zhang Weidong W

Journal of ethnopharmacology 20201008

<h4>Ethnopharmacological relevance</h4>Shexiang Baoxin Pill (SBP) is a composite formula of traditional Chinese medicine used to treat cardiovascular disease (CVD) in the clinic. However, the mechanism of its therapeutic effect on CVD has not been clearly elucidated yet.<h4>Aim of the study</h4>The aim of this study was to investigate the potential cardioprotective mechanism of SBP in the treatment of myocardial infarction (MI) model rats by applying proteomic approach.<h4>Materials and methods< ...[more]

PMID: 33039626

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Project description:<p><strong>OBJECTIVE:</strong> To explore the cardioprotective effects of exercise-derived β-aminoisobutyric (BAIBA) on cardiomyocyte apoptosis and energy metabolism in a rat model of heart failure (HF).</p><p><strong>METHODS:</strong> In male Sprague-Dawley rats (8-week-old), myocardial infarction (MI) was used to induce HF by ligating the left anterior descending branch of the coronary artery. In the Sham group, the coronary artery was threaded but not ligated. After HF development, Sham and HF rats were exercised 60 min daily, 5 days per week on a treadmill for 8 weeks (50-60% maximal intensity) and exercise-induced cardiac remodeling after MI were assessed using echocardiography, hematoxylin and eosin (H&E), Masson’s Trichrome and TUNEL staining for the detection of apoptosis-associated factors in cardiac tissue. High-throughput sequencing and mass spectrometry were used to measure BAIBA production and to explore its cardioprotective effects and molecular actions. To further characterize the cardioprotective effects of BAIBA, an <em>in vitro</em> model of apoptosis was generated by applying H2O2 to H9C2 cells to induce mitochondrial dysfunction. In addition, cells were transfected with either a miR-208b analogue or a miR-208b inhibitor. Apoptosis-related proteins were detected by Western Blotting (WB). ATP production was also assessed by luminometry. After administration of BAIBA and Compound C, the expression of proteins related to apoptosis, mitochondrial function, lipid uptake and β-oxidative were determined. Changes in the levels of reactive oxygen species (ROS) were assessed by fluorescence microscopy. In addition, alterations in membrane potential (δψm) were obtained by confocal microscopy.</p><p><strong>RESULTS:</strong> Rats with HF after MI are accompanied by mitochondrial dysfunction, metabolic stress and apoptosis. Reduced expression of apoptosis-related proteins was observed, together with increased ATP production and reduced mitochondrial dysfunction in the exercised compared with the Sham (non-exercised) HF group. Importantly, exercise increased the production of BAIBA, irrespective of the presence of HF. To assess whether BAIBA had similar effects to exercise in ameliorating HF-induced adverse cardiac remodeling, rats were treated with 75 mg/kg/day of BAIBA and we found BAIBA had a similar cardioprotective effect. Transcriptomic analyses found that the expression of miR-208b was increased after BAIBA administration, and subsequent transfection with an miR-208b analogue ameliorated both the expression of apoptosis-related proteins and energy metabolism in H2O2-treated H9C2 cells. In combining transcriptomic with metabolomic analyses, we identified AMPK as a downstream target for BAIBA in attenuating metabolic stress in HF. Further cell experiments confirmed that BAIBA increased AMPK phosphorylation and had a cardioprotective effect on downstream fatty acid uptake, oxidative efficiency and mitochondrial function, which was prevented by the AMPK inhibitor Compound C.</p><p><strong>CONCLUSION: </strong>Exercise-generated BAIBA can reduce cardiomyocyte metabolic stress and apoptosis induced by mitochondrial dysfunction through the miR-208b/AMPK pathway.</p>

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