Nobiletin Attenuates Pathological Cardiac Remodeling after Myocardial Infarction via Activating PPARγ and PGC1α

Zhou, Yufei; Yin, Ting; Shi, Mengsha; Chen, Mengli; Wu, Xiaodong; Wang, Kai; Cheang, Iokfai; Li, Yanxiu; Shang, Hongcai; Zhang, Haifeng; Li, Xinli

doi:10.1155/2021/9947656

Cited by 13 publications

(7 citation statements)

References 48 publications

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“…Furthermore, our results showed that hesperidin, nobiletin and tangeretin could preserve cardiac systolic function after MI and activate PPARγ (Figure S5A, B). Besides, one of our previous studies suggested that nobiletin attenuated pathological cardiac remodelling after MI via activating PPARγ, 50 which is identical to our findings here. As to tangeretin, several studies indicated that it played an important role in lipid metabolism by increasing PPARγ expression 51,52 .…”

Section: Discussionsupporting

confidence: 92%

Citri Reticulatae Pericarpium alleviates postmyocardial infarction heart failure by upregulating PPARγ expression

Chen

Zhu

et al. 2022

Clin Exp Pharma Physio

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Heart failure after myocardial infarction (MI) is the leading cause of death worldwide. Citri Reticulatae Pericarpium (CRP) is a traditional Chinese herbal medicine that has been used in the clinic for centuries.In this study, we aimed to investigate the roles of CRP in cardiac remodeling and heart failure after MI, as well as the molecular mechanisms involved. MethodsMale C57BL/6 mice aged 8 weeks were subjected to coronary artery ligation to mimic the clinical situation in vivo. Echocardiography was used to assess the systolic function of the mouse heart. Masson trichrome staining and Wheat germ agglutinin (WGA) staining were utilized to determine the brotic area and cross-sectional area of the mouse heart, respectively. Cardiomyocytes and broblasts were isolated from neonatal rats aged 0-3 days in vitro using enzyme digestion. TUNEL staining and EdU staining were performed to evaluate apoptosis and proliferation, respectively. Gene expression changes were analyzed by qRT-PCR, and protein expression changes were assessed by Western blotting. ResultsOur ndings revealed that CRP attenuated cardiac hypertrophy, brosis and apoptosis and alleviated heart failure after MI in vivo. Furthermore, CRP mitigated cardiomyocyte apoptosis and broblast proliferation and differentiation into myo broblasts. In addition, the PPARγ inhibitor T0070907 completely abolished the abovementioned bene cial effects of CRP, and the PPARγ activator rosiglitazone failed to further ameliorate cardiac apoptosis and brosis in vitro. ConclusionCRP alleviates cardiac hypertrophy, brosis, and apoptosis and can ameliorate heart failure after MI via activation of PPARγ.

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Section: Discussionsupporting

confidence: 92%

Citri Reticulatae Pericarpium alleviates postmyocardial infarction heart failure by upregulating PPARγ expression

Chen

Zhu

et al. 2022

Clin Exp Pharma Physio

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“…Cui et al ( 19 ) have confirmed that pathological cardiac hypertrophy could be alleviated by reducing oxidation, inflammation, and apoptosis induced by AngII via Sirt1-mediated activation of AMPK/PGC1α signal molecules. Zhou et al ( 20 ) have found that nobiletin could attenuate post-myocardial infarction pathological cardiac remodeling via upregulating PGC1α. Besides, several new HF drugs exert their function via activating PGC1α.…”

Section: Discussionmentioning

confidence: 99%

The diagnostic value of peroxisome proliferator-activated receptor-γ coactivator-1α in identifying different chronic heart failure phenotypes

Zhang

Zhou

et al. 2022

Front. Cardiovasc. Med.

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BackgroundDespite advances in diagnosing and treating chronic heart failure (HF), the underlying mechanisms in different HF phenotypes remain unclear. Mitochondrial energy metabolism is crucial in HF etiology. Our study aimed to explore the value of metabolic-associated biomarker peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) in identifying different HF phenotypes.MethodsA total of 172 participants were enrolled in the Affiliated Hospital of Xuzhou Medical University and were subsequently divided into four groups based on the European Society of Cardiology HF management guideline: the non-HF control (Control, N = 46), heart failure with reduced ejection fraction (HFrEF, N = 54), heart failure with mildly reduced ejection fraction (HFmrEF, N = 22), and heart failure with preserved ejection fraction (HFpEF, N = 50) groups. Each participant’s baseline data were recorded, blood samples were taken, and echocardiography was conducted. The level of PGC1α expression was determined using an enzyme-linked immunosorbent assay (ELISA) kit. The receiver operative characteristics (ROC) curve was further established in the four groups to assess the diagnostic value for overall HF and each HF phenotype with the calculation of the area under the curve (AUC) and 95% confidence interval (CI).ResultsPGC1α expression was significantly increased in HF patients (315.0 ± 69.58 nmol/L) compared to non-HF participants (233.3 ± 32.69 nmol/L). Considering different HF phenotypes, PGC1α expression was considerably higher in the HFmrEF group (401.6 ± 45.1 nmol/L)than in the other two phenotypes (299.5 ± 62.27 nmol/L for HFrEF and 293.5 ± 56.37 nmol/L for HFpEF, respectively).Furthermore, the AUCs of PGC1α in overall HF and each HF phenotype were all over 0.8, showing the ideal diagnostic value. Additionally, we provided the cut-off criteria for clinical use, which needs further validation. There was no significant correlation between PGC1α and N-terminal (NT)-prohormone B-type natriuretic peptide (BNP)/blood glucose, suggesting that PGC1α might exert a unique function in HF yet in a different pattern.ConclusionWe discovered that PGC1α could be used as a potential biomarker for differentiating HF patients from those without HF and for distinguishing HFmrEF from HFrEF and HFpEF.

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“…Expression of identified DECRs was validated further in clinical samples by RT-qPCR. RNA isolation and RT-qPCR were undertaken as described previously ( Zhou et al, 2021 ). In brief, red blood cell (RBC) lysis buffer (catalog number: C3702; Beyotime Institute of Biotechnology, Shanghai, China) was used to split RBCs.…”

Section: Methodsmentioning

confidence: 99%

Identification and validation of differentially expressed chromatin regulators for diagnosis of aortic dissection using integrated bioinformatics analysis and machine-learning algorithms

et al. 2022

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Background: Aortic dissection (AD) is a life-threatening disease. Chromatin regulators (CRs) are indispensable epigenetic regulators. We aimed to identify differentially expressed chromatin regulators (DECRs) for AD diagnosis.Methods: We downloaded the GSE52093 and GSE190635 datasets from the Gene Expression Omnibus database. Following the merging and processing of datasets, bioinformatics analysis was applied to select candidate DECRs for AD diagnosis: CRs exertion; DECR identification using the “Limma” package; analyses of enrichment of function and signaling pathways; construction of protein–protein interaction (PPI) networks; application of machine-learning algorithms; evaluation of receiver operating characteristic (ROC) curves. GSE98770 served as the validation dataset to filter DECRs. Moreover, we collected peripheral-blood samples to further validate expression of DECRs by real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Finally, a nomogram was built for clinical use.Results: A total of 841 CRs were extracted from the merged dataset. Analyses of functional enrichment of 23 DECRs identified using Limma showed that DECRs were enriched mainly in epigenetic-regulation processes. From the PPI network, 17 DECRs were selected as node DECRs. After machine-learning calculations, eight DECRs were chosen from the intersection of 13 DECRs identified using support vector machine recursive feature elimination (SVM-RFE) and the top-10 DECRs selected using random forest. DECR expression between the control group and AD group were considerably different. Moreover, the area under the ROC curve (AUC) of each DECR was >0.75, and four DECRs (tumor protein 53 (TP53), chromobox protein homolog 7 (CBX7), Janus kinase 2 (JAK2) and cyclin-dependent kinase 5 (CDK5)) were selected as candidate biomarkers after validation using the external dataset and clinical samples. Furthermore, a nomogram with robust diagnostic value was established (AUC = 0.960).Conclusion: TP53, CBX7, JAK2, and CDK5 might serve as diagnostic DECRs for AD diagnosis. These DECRs were enriched predominantly in regulating epigenetic processes.

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Nobiletin Attenuates Pathological Cardiac Remodeling after Myocardial Infarction via Activating PPARγ and PGC1α

Cited by 13 publications

References 48 publications

Citri Reticulatae Pericarpium alleviates postmyocardial infarction heart failure by upregulating PPARγ expression

Citri Reticulatae Pericarpium alleviates postmyocardial infarction heart failure by upregulating PPARγ expression

The diagnostic value of peroxisome proliferator-activated receptor-γ coactivator-1α in identifying different chronic heart failure phenotypes

Identification and validation of differentially expressed chromatin regulators for diagnosis of aortic dissection using integrated bioinformatics analysis and machine-learning algorithms

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