AFC1 compound attenuated MI/R-induced ventricular remodeling via inhibiting PDGFR and STAT pathway

Jie Liu; Xiaohui Zhou; Qingshu Meng; Kevin W. Huang; Jing Liu; Jinjun Tie; Rulin Zhuang; Guohan Chen; Yuhui Zhang; Lu Wei; Li Huang; Chun Guang Li; Binghui Wang; Huimin Fan; Zhongmin Liu

doi:10.3389/fphar.2019.01142

AFC1 compound attenuated MI/R-induced ventricular remodeling via inhibiting PDGFR and STAT pathway

Jie Liu, Xiaohui Zhou, Qingshu Meng, Kevin W. Huang, Jing Liu, Jinjun Tie, Rulin Zhuang, Guohan Chen, Yuhui Zhang, Lu Wei, Li Huang, Chun Guang Li, Binghui Wang, Huimin Fan, Zhongmin Liu

Western Sydney University

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	1142
Number of pages	14
Journal	Frontiers in Pharmacology
Volume	10
DOIs	https://doi.org/10.3389/fphar.2019.01142
Publication status	Published - 2019

Open Access - Access Right Statement

Copyright © 2019 Liu, Zhou, Meng, Huang, Liu, Tie, Zhuang, Chen, Zhang, Wei, Huang, Li, Wang, Fan and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (https://creativecommons.org/licenses/by/4.0/). 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.

Keywords

myocardial reperfusion
platelet-derived growth factor
ventricular remodeling

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10.3389/fphar.2019.01142

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@article{56606e5063e5475ebafd797cfb800a84,

title = "AFC1 compound attenuated MI/R-induced ventricular remodeling via inhibiting PDGFR and STAT pathway",

abstract = "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.",

keywords = "myocardial reperfusion, platelet-derived growth factor, ventricular remodeling",

author = "Jie Liu and Xiaohui Zhou and Qingshu Meng and Huang, {Kevin W.} and Jing Liu and Jinjun Tie and Rulin Zhuang and Guohan Chen and Yuhui Zhang and Lu Wei and Li Huang and Li, {Chun Guang} and Binghui Wang and Huimin Fan and Zhongmin Liu",

year = "2019",

doi = "10.3389/fphar.2019.01142",

language = "English",

volume = "10",

journal = "Frontiers in Pharmacology",

issn = "1663-9812",

publisher = "Frontiers Research Foundation",

}

TY - JOUR

T1 - AFC1 compound attenuated MI/R-induced ventricular remodeling via inhibiting PDGFR and STAT pathway

AU - Liu, Jie

AU - Zhou, Xiaohui

AU - Meng, Qingshu

AU - Huang, Kevin W.

AU - Liu, Jing

AU - Tie, Jinjun

AU - Zhuang, Rulin

AU - Chen, Guohan

AU - Zhang, Yuhui

AU - Wei, Lu

AU - Huang, Li

AU - Li, Chun Guang

AU - Wang, Binghui

AU - Fan, Huimin

AU - Liu, Zhongmin

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - myocardial reperfusion

KW - platelet-derived growth factor

KW - ventricular remodeling

UR - https://hdl.handle.net/1959.7/uws:53191

U2 - 10.3389/fphar.2019.01142

DO - 10.3389/fphar.2019.01142

M3 - Article

SN - 1663-9812

VL - 10

JO - Frontiers in Pharmacology

JF - Frontiers in Pharmacology

M1 - 1142

ER -

AFC1 compound attenuated MI/R-induced ventricular remodeling via inhibiting PDGFR and STAT pathway

Abstract

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Keywords

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