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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
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.
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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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