Resveratrol Inhibits High Glucose-Induced H9c2 Cardiomyocyte Hypertrophy and Damage via RAGE-Dependent Inhibition of the NF-κB and TGF-β1/Smad3 Pathways.
{"title":"Resveratrol Inhibits High Glucose-Induced H9c2 Cardiomyocyte Hypertrophy and Damage via RAGE-Dependent Inhibition of the NF-<i>κ</i>B and TGF-<i>β</i>1/Smad3 Pathways.","authors":"Yanzhou Zhu, Fuling Wu, Qin Yang, Haixing Feng, Dingli Xu","doi":"10.1155/2022/7781910","DOIUrl":null,"url":null,"abstract":"<p><p>Hyperglycaemia is associated with the development of cardiac vascular disease. Resveratrol (RES) is a naturally occurring polyphenolic compound that possesses many biological properties, including anti-inflammatory properties and antioxidation functions. Our study aimed to explore the RES's protective roles on high glucose (HG)-induced H9c2 cells and the underlying mechanisms. Small-molecule inhibitors, western blotting (WB), as well as reverse-transcription PCR (RT-PCR) were employed to investigate the mechanisms underlying HG-induced damage in H9c2 cells. RES (40 <i>μ</i>g/mL) treatment significantly alleviated HG-induced cardiac hypertrophy and cardiac dysfunction. RES abated the HG-induced increase in the levels of extracellular matrix (ECM) components and inflammatory cytokines, reducing ECM accumulation and inflammatory responses. Additionally, RES administration prevented HG-induced mitochondrion-mediated cardiac apoptosis of myocardial cells. In terms of mechanisms, we demonstrated that RES ameliorated the HG-induced overexpression of receptor for advanced glycation endproducts (RAGE) and downregulation of NF-<i>κ</i>B signalling. Moreover, RES inhibited HG-induced cardiac fibrosis by inhibiting transforming growth factor beta 1 (TGF-<i>β</i>1)/Smad3-mediated ECM synthesis in cultured H9c2 cardiomyocytes. Further studies revealed that the effects of RES against HG-induced upregulation of NF-<i>κ</i>B and TGF-<i>β</i>1/Smad3 pathways were similar to those of FPS-ZM1, a RAGE inhibitor. Collectively, the results implied that RES might help alleviate HG-induced cardiotoxicity via RAGE-dependent downregulation of the NF-<i>κ</i>B and TGF-<i>β</i>/Smad3 pathways. This study provided evidence that RES can be developed as a promising cardioprotective drug.</p>","PeriodicalId":44104,"journal":{"name":"EURO Journal on Decision Processes","volume":"3 1","pages":"7781910"},"PeriodicalIF":2.3000,"publicationDate":"2022-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8896917/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"EURO Journal on Decision Processes","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1155/2022/7781910","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"MANAGEMENT","Score":null,"Total":0}
引用次数: 0
Abstract
Hyperglycaemia is associated with the development of cardiac vascular disease. Resveratrol (RES) is a naturally occurring polyphenolic compound that possesses many biological properties, including anti-inflammatory properties and antioxidation functions. Our study aimed to explore the RES's protective roles on high glucose (HG)-induced H9c2 cells and the underlying mechanisms. Small-molecule inhibitors, western blotting (WB), as well as reverse-transcription PCR (RT-PCR) were employed to investigate the mechanisms underlying HG-induced damage in H9c2 cells. RES (40 μg/mL) treatment significantly alleviated HG-induced cardiac hypertrophy and cardiac dysfunction. RES abated the HG-induced increase in the levels of extracellular matrix (ECM) components and inflammatory cytokines, reducing ECM accumulation and inflammatory responses. Additionally, RES administration prevented HG-induced mitochondrion-mediated cardiac apoptosis of myocardial cells. In terms of mechanisms, we demonstrated that RES ameliorated the HG-induced overexpression of receptor for advanced glycation endproducts (RAGE) and downregulation of NF-κB signalling. Moreover, RES inhibited HG-induced cardiac fibrosis by inhibiting transforming growth factor beta 1 (TGF-β1)/Smad3-mediated ECM synthesis in cultured H9c2 cardiomyocytes. Further studies revealed that the effects of RES against HG-induced upregulation of NF-κB and TGF-β1/Smad3 pathways were similar to those of FPS-ZM1, a RAGE inhibitor. Collectively, the results implied that RES might help alleviate HG-induced cardiotoxicity via RAGE-dependent downregulation of the NF-κB and TGF-β/Smad3 pathways. This study provided evidence that RES can be developed as a promising cardioprotective drug.