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Metformin Attenuates Cardiac Hypertrophy Via the HIF-1α/PPAR-γ Signaling Pathway in High-Fat Diet Rats
Coronary artery disease (CAD) and cardiac hypertrophy (CH) are two main causes of ischemic heart disease. Acute CAD may lead to left ventricular hypertrophy (LVH). Long-term and sustained CH is harmful and can gradually develop into cardiac insufficiency and heart failure. It is known that metformin...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271627/ https://www.ncbi.nlm.nih.gov/pubmed/35833024 http://dx.doi.org/10.3389/fphar.2022.919202 |
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author | Liu, Yuansheng Zhang, Qian Yang, Lei Tian, Wencong Yang, Yinan Xie, Yuhang Li, Jing Yang, Liang Gao, Yang Xu, Yang Liu, Jie Wang, Yachen Yan, Jie Li, Guoxun Shen, Yanna Qi, Zhi |
author_facet | Liu, Yuansheng Zhang, Qian Yang, Lei Tian, Wencong Yang, Yinan Xie, Yuhang Li, Jing Yang, Liang Gao, Yang Xu, Yang Liu, Jie Wang, Yachen Yan, Jie Li, Guoxun Shen, Yanna Qi, Zhi |
author_sort | Liu, Yuansheng |
collection | PubMed |
description | Coronary artery disease (CAD) and cardiac hypertrophy (CH) are two main causes of ischemic heart disease. Acute CAD may lead to left ventricular hypertrophy (LVH). Long-term and sustained CH is harmful and can gradually develop into cardiac insufficiency and heart failure. It is known that metformin (Met) can alleviate CH; however, the molecular mechanism is not fully understood. Herein, we used high-fat diet (HFD) rats and H9c2 cells to induce CH and clarify the potential mechanism of Met on CH. We found that Met treatment significantly decreased the cardiomyocyte size, reduced lactate dehydrogenase (LDH) release, and downregulated the expressions of hypertrophy markers ANP, VEGF-A, and GLUT1 either in vivo or in vitro. Meanwhile, the protein levels of HIF-1α and PPAR-γ were both decreased after Met treatment, and administrations of their agonists, deferoxamine (DFO) or rosiglitazone (Ros), markedly abolished the protective effect of Met on CH. In addition, DFO treatment upregulated the expression of PPAR-γ, whereas Ros treatment did not affect the expression of HIF-1α. In conclusion, Met attenuates CH via the HIF-1α/PPAR-γ signaling pathway. |
format | Online Article Text |
id | pubmed-9271627 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92716272022-07-12 Metformin Attenuates Cardiac Hypertrophy Via the HIF-1α/PPAR-γ Signaling Pathway in High-Fat Diet Rats Liu, Yuansheng Zhang, Qian Yang, Lei Tian, Wencong Yang, Yinan Xie, Yuhang Li, Jing Yang, Liang Gao, Yang Xu, Yang Liu, Jie Wang, Yachen Yan, Jie Li, Guoxun Shen, Yanna Qi, Zhi Front Pharmacol Pharmacology Coronary artery disease (CAD) and cardiac hypertrophy (CH) are two main causes of ischemic heart disease. Acute CAD may lead to left ventricular hypertrophy (LVH). Long-term and sustained CH is harmful and can gradually develop into cardiac insufficiency and heart failure. It is known that metformin (Met) can alleviate CH; however, the molecular mechanism is not fully understood. Herein, we used high-fat diet (HFD) rats and H9c2 cells to induce CH and clarify the potential mechanism of Met on CH. We found that Met treatment significantly decreased the cardiomyocyte size, reduced lactate dehydrogenase (LDH) release, and downregulated the expressions of hypertrophy markers ANP, VEGF-A, and GLUT1 either in vivo or in vitro. Meanwhile, the protein levels of HIF-1α and PPAR-γ were both decreased after Met treatment, and administrations of their agonists, deferoxamine (DFO) or rosiglitazone (Ros), markedly abolished the protective effect of Met on CH. In addition, DFO treatment upregulated the expression of PPAR-γ, whereas Ros treatment did not affect the expression of HIF-1α. In conclusion, Met attenuates CH via the HIF-1α/PPAR-γ signaling pathway. Frontiers Media S.A. 2022-06-27 /pmc/articles/PMC9271627/ /pubmed/35833024 http://dx.doi.org/10.3389/fphar.2022.919202 Text en Copyright © 2022 Liu, Zhang, Yang, Tian, Yang, Xie, Li, Yang, Gao, Xu, Liu, Wang, Yan, Li, Shen and Qi. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Liu, Yuansheng Zhang, Qian Yang, Lei Tian, Wencong Yang, Yinan Xie, Yuhang Li, Jing Yang, Liang Gao, Yang Xu, Yang Liu, Jie Wang, Yachen Yan, Jie Li, Guoxun Shen, Yanna Qi, Zhi Metformin Attenuates Cardiac Hypertrophy Via the HIF-1α/PPAR-γ Signaling Pathway in High-Fat Diet Rats |
title | Metformin Attenuates Cardiac Hypertrophy Via the HIF-1α/PPAR-γ Signaling Pathway in High-Fat Diet Rats |
title_full | Metformin Attenuates Cardiac Hypertrophy Via the HIF-1α/PPAR-γ Signaling Pathway in High-Fat Diet Rats |
title_fullStr | Metformin Attenuates Cardiac Hypertrophy Via the HIF-1α/PPAR-γ Signaling Pathway in High-Fat Diet Rats |
title_full_unstemmed | Metformin Attenuates Cardiac Hypertrophy Via the HIF-1α/PPAR-γ Signaling Pathway in High-Fat Diet Rats |
title_short | Metformin Attenuates Cardiac Hypertrophy Via the HIF-1α/PPAR-γ Signaling Pathway in High-Fat Diet Rats |
title_sort | metformin attenuates cardiac hypertrophy via the hif-1α/ppar-γ signaling pathway in high-fat diet rats |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271627/ https://www.ncbi.nlm.nih.gov/pubmed/35833024 http://dx.doi.org/10.3389/fphar.2022.919202 |
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