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PFKFB3 Inhibitor 3PO Reduces Cardiac Remodeling after Myocardial Infarction by Regulating the TGF-β1/SMAD2/3 Pathway
Adverse cardiac remodeling, including cardiac fibrosis, after myocardial infarction (MI) is a major cause of long-term heart failure. 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), an enzyme that regulates glucose metabolism, also plays an important role in various fibrotic and card...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10377206/ https://www.ncbi.nlm.nih.gov/pubmed/37509108 http://dx.doi.org/10.3390/biom13071072 |
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author | Yang, Qian Zong, Xiao Zhuang, Lingfang Pan, Roubai Tudi, Xierenayi Fan, Qin Tao, Rong |
author_facet | Yang, Qian Zong, Xiao Zhuang, Lingfang Pan, Roubai Tudi, Xierenayi Fan, Qin Tao, Rong |
author_sort | Yang, Qian |
collection | PubMed |
description | Adverse cardiac remodeling, including cardiac fibrosis, after myocardial infarction (MI) is a major cause of long-term heart failure. 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), an enzyme that regulates glucose metabolism, also plays an important role in various fibrotic and cardiovascular diseases. However, its effects on MI remain unknown. Here, PFKFB3 inhibitor 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) and a permanent left anterior descending ligation mouse model were used to explore the functional role of PFKFB3 in MI. We showed that PFKFB3 expression increased significantly in the area of cardiac infarction during the early phase after MI, peaking on day 3. 3PO treatment markedly improved cardiac function, accompanied by decreased infarction size and collagen density in the infarct area. Meanwhile, 3PO attenuated cardiac fibrosis after MI by reducing the expression of collagen and fibronectin in murine hearts. Notably, 3PO reduced PFKFB3 expression and inhibited the transforming growth factor-beta 1/mothers against the decapentaplegic homolog 2/3 (TGF-β1/SMAD2/3) signaling pathway to inhibit cardiac fibrosis after MI. Moreover, PFKFB3 expression in neonatal rat cardiac fibroblasts (NRCFs) increased significantly after MI and under hypoxia, whereas 3PO alleviated the migratory capacity and activation of NRCFs induced by TGF-β1. In conclusion, 3PO effectively reduced fibrosis and improved adverse cardiac remodeling after MI, suggesting PFKFB3 inhibition as a novel therapeutic strategy to reduce the incidence of chronic heart failure following MI. |
format | Online Article Text |
id | pubmed-10377206 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-103772062023-07-29 PFKFB3 Inhibitor 3PO Reduces Cardiac Remodeling after Myocardial Infarction by Regulating the TGF-β1/SMAD2/3 Pathway Yang, Qian Zong, Xiao Zhuang, Lingfang Pan, Roubai Tudi, Xierenayi Fan, Qin Tao, Rong Biomolecules Article Adverse cardiac remodeling, including cardiac fibrosis, after myocardial infarction (MI) is a major cause of long-term heart failure. 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), an enzyme that regulates glucose metabolism, also plays an important role in various fibrotic and cardiovascular diseases. However, its effects on MI remain unknown. Here, PFKFB3 inhibitor 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) and a permanent left anterior descending ligation mouse model were used to explore the functional role of PFKFB3 in MI. We showed that PFKFB3 expression increased significantly in the area of cardiac infarction during the early phase after MI, peaking on day 3. 3PO treatment markedly improved cardiac function, accompanied by decreased infarction size and collagen density in the infarct area. Meanwhile, 3PO attenuated cardiac fibrosis after MI by reducing the expression of collagen and fibronectin in murine hearts. Notably, 3PO reduced PFKFB3 expression and inhibited the transforming growth factor-beta 1/mothers against the decapentaplegic homolog 2/3 (TGF-β1/SMAD2/3) signaling pathway to inhibit cardiac fibrosis after MI. Moreover, PFKFB3 expression in neonatal rat cardiac fibroblasts (NRCFs) increased significantly after MI and under hypoxia, whereas 3PO alleviated the migratory capacity and activation of NRCFs induced by TGF-β1. In conclusion, 3PO effectively reduced fibrosis and improved adverse cardiac remodeling after MI, suggesting PFKFB3 inhibition as a novel therapeutic strategy to reduce the incidence of chronic heart failure following MI. MDPI 2023-07-03 /pmc/articles/PMC10377206/ /pubmed/37509108 http://dx.doi.org/10.3390/biom13071072 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Yang, Qian Zong, Xiao Zhuang, Lingfang Pan, Roubai Tudi, Xierenayi Fan, Qin Tao, Rong PFKFB3 Inhibitor 3PO Reduces Cardiac Remodeling after Myocardial Infarction by Regulating the TGF-β1/SMAD2/3 Pathway |
title | PFKFB3 Inhibitor 3PO Reduces Cardiac Remodeling after Myocardial Infarction by Regulating the TGF-β1/SMAD2/3 Pathway |
title_full | PFKFB3 Inhibitor 3PO Reduces Cardiac Remodeling after Myocardial Infarction by Regulating the TGF-β1/SMAD2/3 Pathway |
title_fullStr | PFKFB3 Inhibitor 3PO Reduces Cardiac Remodeling after Myocardial Infarction by Regulating the TGF-β1/SMAD2/3 Pathway |
title_full_unstemmed | PFKFB3 Inhibitor 3PO Reduces Cardiac Remodeling after Myocardial Infarction by Regulating the TGF-β1/SMAD2/3 Pathway |
title_short | PFKFB3 Inhibitor 3PO Reduces Cardiac Remodeling after Myocardial Infarction by Regulating the TGF-β1/SMAD2/3 Pathway |
title_sort | pfkfb3 inhibitor 3po reduces cardiac remodeling after myocardial infarction by regulating the tgf-β1/smad2/3 pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10377206/ https://www.ncbi.nlm.nih.gov/pubmed/37509108 http://dx.doi.org/10.3390/biom13071072 |
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