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

IF 3.5 3区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

PPAR Research Pub Date : 2021-08-06 eCollection Date: 2021-01-01 DOI:10.1155/2021/9947656

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

{"title":"Nobiletin Attenuates Pathological Cardiac Remodeling after Myocardial Infarction via Activating PPARγ and PGC1α.","authors":"Yufei Zhou, Ting Yin, Mengsha Shi, Mengli Chen, Xiaodong Wu, Kai Wang, Iokfai Cheang, Yanxiu Li, Hongcai Shang, Haifeng Zhang, Xinli Li","doi":"10.1155/2021/9947656","DOIUrl":null,"url":null,"abstract":"Materials and methods: C57BL/6 mice were treated with coronary artery ligation to generate an MI model, followed by treatment for 3 weeks with NOB (50 mg/kg/d) or vehicle (50 mg/kg/d), with or without the peroxisome proliferator-activated receptor gamma (PPARγ) inhibitor T0070907 (1 mg/kg/d). Cardiac function (echocardiography, survival rate, Evans blue, and triphenyl tetrazolium chloride staining), fibrosis (Masson's trichrome staining, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot (WB)), hypertrophy (haematoxylin-eosin staining, wheat germ agglutinin staining, and qRT-PCR), and apoptosis (WB and terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) staining) were evaluated. Hypoxia-induced apoptosis (TUNEL, WB) and phenylephrine- (PE-) induced pathological hypertrophy (immunofluorescence staining, qRT-PCR) models were established in primary neonatal rat ventricular myocytes (NRVMs). The effects of NOB with or without T0070907 were examined for the expression of PPARγ and PPARγ coactivator 1α (PGC1α) by WB in mice and NRVMs. The potential downstream effectors of PPARγ were further analyzed by WB in mice.Results: Following MI in mice, NOB intervention enhanced cardiac function across three predominant dimensions of pathological cardiac remodeling, which reflected in decreasing cardiac fibrosis, apoptosis, and hypertrophy decompensation. NOB intervention also alleviated apoptosis and hypertrophy in NRVMs. NOB intervention upregulated PPARγ and PGC1α in vivo and in vitro. Furthermore, the PPARγ inhibitor abolished the protective effects of NOB against pathological cardiac remodeling during the progression from MI to CHF. The potential downstream effectors of PPARγ were nuclear factor erythroid 2-related factor 2 (Nrf-2) and heme oxygenase 1 (HO-1).Conclusions: Our findings suggested that NOB alleviates pathological cardiac remodeling after MI via PPARγ and PGC1α upregulation.","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2021-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373512/pdf/","citationCount":"9","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"PPAR Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1155/2021/9947656","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2021/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}

引用次数: 9

Abstract

Materials and methods: C57BL/6 mice were treated with coronary artery ligation to generate an MI model, followed by treatment for 3 weeks with NOB (50 mg/kg/d) or vehicle (50 mg/kg/d), with or without the peroxisome proliferator-activated receptor gamma (PPARγ) inhibitor T0070907 (1 mg/kg/d). Cardiac function (echocardiography, survival rate, Evans blue, and triphenyl tetrazolium chloride staining), fibrosis (Masson's trichrome staining, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot (WB)), hypertrophy (haematoxylin-eosin staining, wheat germ agglutinin staining, and qRT-PCR), and apoptosis (WB and terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) staining) were evaluated. Hypoxia-induced apoptosis (TUNEL, WB) and phenylephrine- (PE-) induced pathological hypertrophy (immunofluorescence staining, qRT-PCR) models were established in primary neonatal rat ventricular myocytes (NRVMs). The effects of NOB with or without T0070907 were examined for the expression of PPARγ and PPARγ coactivator 1α (PGC1α) by WB in mice and NRVMs. The potential downstream effectors of PPARγ were further analyzed by WB in mice.

Results: Following MI in mice, NOB intervention enhanced cardiac function across three predominant dimensions of pathological cardiac remodeling, which reflected in decreasing cardiac fibrosis, apoptosis, and hypertrophy decompensation. NOB intervention also alleviated apoptosis and hypertrophy in NRVMs. NOB intervention upregulated PPARγ and PGC1α in vivo and in vitro. Furthermore, the PPARγ inhibitor abolished the protective effects of NOB against pathological cardiac remodeling during the progression from MI to CHF. The potential downstream effectors of PPARγ were nuclear factor erythroid 2-related factor 2 (Nrf-2) and heme oxygenase 1 (HO-1).

Conclusions: Our findings suggested that NOB alleviates pathological cardiac remodeling after MI via PPARγ and PGC1α upregulation.

Abstract Image

查看原文本刊更多论文

诺比列素通过激活PPARγ和PGC1α减轻心肌梗死后的病理性心脏重构。

材料和方法:C57BL/6小鼠冠脉结扎制备心肌梗死模型，随后给予NOB (50 mg/kg/d)或对照(50 mg/kg/d)，加或不加过氧化物酶体增殖物激活受体γ (PPARγ)抑制剂T0070907 (1 mg/kg/d)治疗3周。评估心功能(超声心动图、存活率、埃文思蓝染色、三苯基氯化四氮唑染色)、纤维化(马松三色染色、定量实时聚合酶链反应(qRT-PCR)和western blot (WB))、肥厚(苏木精-伊红染色、小麦胚凝集素染色和qRT-PCR)和凋亡(WB和末端脱氧核苷酸转移酶dUTP镍端标记(TUNEL)染色)。建立了新生大鼠心室肌细胞(nrvm)缺氧诱导凋亡(TUNEL, WB)和苯肾上腺素(PE-)诱导病理性肥大(qRT-PCR)模型。研究了NOB加T0070907或不加T0070907对小鼠和nrvm中PPARγ和PPARγ共激活因子1α (PGC1α)表达的影响。用WB进一步分析了PPARγ的潜在下游效应。结果:小鼠心肌梗死后，NOB干预在病理性心脏重塑的三个主要维度上增强了心功能，这反映在心脏纤维化、细胞凋亡和肥厚失代偿的减少。NOB干预还可减轻nrvm的凋亡和肥大。NOB干预在体内和体外上调PPARγ和PGC1α。此外，PPARγ抑制剂消除了NOB在心肌梗死到心力衰竭过程中对病理性心脏重塑的保护作用。PPARγ的潜在下游效应物是核因子-红细胞2相关因子2 (Nrf-2)和血红素加氧酶1 (HO-1)。结论:我们的研究结果表明，NOB通过上调PPARγ和PGC1α来减轻心肌梗死后的病理性心脏重构。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

PPAR Research MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

6.20

自引率

3.40%

发文量

审稿时长

12 months

期刊介绍： PPAR Research is a peer-reviewed, Open Access journal that publishes original research and review articles on advances in basic research focusing on mechanisms involved in the activation of peroxisome proliferator-activated receptors (PPARs), as well as their role in the regulation of cellular differentiation, development, energy homeostasis and metabolic function. The journal also welcomes preclinical and clinical trials of drugs that can modulate PPAR activity, with a view to treating chronic diseases and disorders such as dyslipidemia, diabetes, adipocyte differentiation, inflammation, cancer, lung diseases, neurodegenerative disorders, and obesity.