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AFC1 Compound Attenuated MI/R-Induced Ventricular Remodeling via Inhibiting PDGFR and STAT Pathway
Background: Effective interventions to improve the outcome of patients subjected to myocardial ischemia reperfusion (MI/R) are urgent in clinical settings. Tanshinone IIA (TSA) is reported to attenuate myocardial injury and improve ventricular remodeling post MI/R. Here, we evaluated the efficacy of...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6803464/ https://www.ncbi.nlm.nih.gov/pubmed/31680946 http://dx.doi.org/10.3389/fphar.2019.01142 |
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author | Liu, Jie Zhou, Xiaohui Meng, Qingshu Huang, Kevin W. Liu, Jing Tie, Jinjun Zhuang, Rulin Chen, Guohan Zhang, Yuhui Wei, Lu Huang, Li Li, Chun Guang Wang, Binghui Fan, Huimin Liu, Zhongmin |
author_facet | Liu, Jie Zhou, Xiaohui Meng, Qingshu Huang, Kevin W. Liu, Jing Tie, Jinjun Zhuang, Rulin Chen, Guohan Zhang, Yuhui Wei, Lu Huang, Li Li, Chun Guang Wang, Binghui Fan, Huimin Liu, Zhongmin |
author_sort | Liu, Jie |
collection | PubMed |
description | Background: Effective interventions to improve the outcome of patients subjected to myocardial ischemia reperfusion (MI/R) are urgent in clinical settings. Tanshinone IIA (TSA) is reported to attenuate myocardial injury and improve ventricular remodeling post MI/R. Here, we evaluated the efficacy of AFC1 compound that is similar to TSA structure in murine MI/R models. We found that AFC1 had a comparable effect of improving murine cardiac function after MI/R while it was superior to TSA in safety profile. Administration of AFC1 reduced reactive oxygen species (ROS) production, inflammatory cells infiltration, and the expression of platelet derived growth factor receptors (PDGFR) in infarcted myocardium. Treatment with AFC1 also attenuated MI/R-induced cardiac remodeling and contributed to the recovery of cardiac function. Additionally, AFC1 reversed the elevation of PDGFR expression induced by PDGF-AB in both neonatal rat cardiomyocytes (NCMs) and neonatal rat cardiac fibroblasts (NCFs) and suppressed PDGF-AB induced NCM hypertrophy via STAT3 pathway and NCF collagen synthesis through p38-MAPK signaling in vitro. Similarly, AFC1 may contribute to the recovery of cardiac function in mice post MI/R via suppressing STAT signaling. Our results confirmed that AFC1 exerts anti-hypertrophic and anti-fibrotic effects against MI/R-induced cardiac remodeling, and suggest that AFC1 may have a promising potential in improving the outcome of patients who suffered from MI/R. |
format | Online Article Text |
id | pubmed-6803464 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-68034642019-11-03 AFC1 Compound Attenuated MI/R-Induced Ventricular Remodeling via Inhibiting PDGFR and STAT Pathway Liu, Jie Zhou, Xiaohui Meng, Qingshu Huang, Kevin W. Liu, Jing Tie, Jinjun Zhuang, Rulin Chen, Guohan Zhang, Yuhui Wei, Lu Huang, Li Li, Chun Guang Wang, Binghui Fan, Huimin Liu, Zhongmin Front Pharmacol Pharmacology Background: Effective interventions to improve the outcome of patients subjected to myocardial ischemia reperfusion (MI/R) are urgent in clinical settings. Tanshinone IIA (TSA) is reported to attenuate myocardial injury and improve ventricular remodeling post MI/R. Here, we evaluated the efficacy of AFC1 compound that is similar to TSA structure in murine MI/R models. We found that AFC1 had a comparable effect of improving murine cardiac function after MI/R while it was superior to TSA in safety profile. Administration of AFC1 reduced reactive oxygen species (ROS) production, inflammatory cells infiltration, and the expression of platelet derived growth factor receptors (PDGFR) in infarcted myocardium. Treatment with AFC1 also attenuated MI/R-induced cardiac remodeling and contributed to the recovery of cardiac function. Additionally, AFC1 reversed the elevation of PDGFR expression induced by PDGF-AB in both neonatal rat cardiomyocytes (NCMs) and neonatal rat cardiac fibroblasts (NCFs) and suppressed PDGF-AB induced NCM hypertrophy via STAT3 pathway and NCF collagen synthesis through p38-MAPK signaling in vitro. Similarly, AFC1 may contribute to the recovery of cardiac function in mice post MI/R via suppressing STAT signaling. Our results confirmed that AFC1 exerts anti-hypertrophic and anti-fibrotic effects against MI/R-induced cardiac remodeling, and suggest that AFC1 may have a promising potential in improving the outcome of patients who suffered from MI/R. Frontiers Media S.A. 2019-10-15 /pmc/articles/PMC6803464/ /pubmed/31680946 http://dx.doi.org/10.3389/fphar.2019.01142 Text en Copyright © 2019 Liu, Zhou, Meng, Huang, Liu, Tie, Zhuang, Chen, Zhang, Wei, Huang, Li, Wang, Fan and Liu http://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, Jie Zhou, Xiaohui Meng, Qingshu Huang, Kevin W. Liu, Jing Tie, Jinjun Zhuang, Rulin Chen, Guohan Zhang, Yuhui Wei, Lu Huang, Li Li, Chun Guang Wang, Binghui Fan, Huimin Liu, Zhongmin AFC1 Compound Attenuated MI/R-Induced Ventricular Remodeling via Inhibiting PDGFR and STAT Pathway |
title | AFC1 Compound Attenuated MI/R-Induced Ventricular Remodeling via Inhibiting PDGFR and STAT Pathway |
title_full | AFC1 Compound Attenuated MI/R-Induced Ventricular Remodeling via Inhibiting PDGFR and STAT Pathway |
title_fullStr | AFC1 Compound Attenuated MI/R-Induced Ventricular Remodeling via Inhibiting PDGFR and STAT Pathway |
title_full_unstemmed | AFC1 Compound Attenuated MI/R-Induced Ventricular Remodeling via Inhibiting PDGFR and STAT Pathway |
title_short | AFC1 Compound Attenuated MI/R-Induced Ventricular Remodeling via Inhibiting PDGFR and STAT Pathway |
title_sort | afc1 compound attenuated mi/r-induced ventricular remodeling via inhibiting pdgfr and stat pathway |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6803464/ https://www.ncbi.nlm.nih.gov/pubmed/31680946 http://dx.doi.org/10.3389/fphar.2019.01142 |
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