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Novel EGFR inhibitors attenuate cardiac hypertrophy induced by angiotensin II
by
Peng, Kesong
, Liang, Guang
, Qian, Yuanyuan
, Wang, Jingying
, Tian, Xinqiao
, Skibba, Melissa
, Liu, Zhiguo
, Zou, Chunpeng
, Xu, Zheng
, Li, Xiaokun
in
AKT protein
/ Angiotensin
/ Angiotensin II
/ Animals
/ Atherosclerosis
/ Cancer therapies
/ cardiac hypertrophy
/ Cardiomegaly - chemically induced
/ Cardiomegaly - drug therapy
/ Cardiomyocytes
/ Cardiotonic Agents - pharmacology
/ Cardiotonic Agents - therapeutic use
/ Cardiovascular diseases
/ Cardiovascular system
/ Cell Line
/ Congestive heart failure
/ Coronary artery disease
/ c‐Src
/ Disease prevention
/ Drug Evaluation, Preclinical
/ Epidermal growth factor
/ Epidermal Growth Factor - physiology
/ epidermal growth factor receptor
/ Epidermal growth factor receptors
/ Experiments
/ Extracellular signal-regulated kinase
/ Fibrosis
/ Gene Knockdown Techniques
/ Heart
/ Hypertrophy
/ Kinases
/ Laboratories
/ Mice, Inbred C57BL
/ Molecular modelling
/ Myocytes, Cardiac - drug effects
/ Myocytes, Cardiac - physiology
/ Oral administration
/ Original
/ Phosphorylation
/ Physiology
/ Proteins
/ Quinazolines - pharmacology
/ Quinazolines - therapeutic use
/ Rats
/ Receptor, Epidermal Growth Factor - antagonists & inhibitors
/ Receptor, Epidermal Growth Factor - genetics
/ Receptor, Epidermal Growth Factor - metabolism
/ Risk factors
/ Signal transduction
/ small‐molecule inhibitor
/ Src protein
/ Studies
/ Tyrphostins - pharmacology
/ Tyrphostins - therapeutic use
2016
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Novel EGFR inhibitors attenuate cardiac hypertrophy induced by angiotensin II
by
Peng, Kesong
, Liang, Guang
, Qian, Yuanyuan
, Wang, Jingying
, Tian, Xinqiao
, Skibba, Melissa
, Liu, Zhiguo
, Zou, Chunpeng
, Xu, Zheng
, Li, Xiaokun
in
AKT protein
/ Angiotensin
/ Angiotensin II
/ Animals
/ Atherosclerosis
/ Cancer therapies
/ cardiac hypertrophy
/ Cardiomegaly - chemically induced
/ Cardiomegaly - drug therapy
/ Cardiomyocytes
/ Cardiotonic Agents - pharmacology
/ Cardiotonic Agents - therapeutic use
/ Cardiovascular diseases
/ Cardiovascular system
/ Cell Line
/ Congestive heart failure
/ Coronary artery disease
/ c‐Src
/ Disease prevention
/ Drug Evaluation, Preclinical
/ Epidermal growth factor
/ Epidermal Growth Factor - physiology
/ epidermal growth factor receptor
/ Epidermal growth factor receptors
/ Experiments
/ Extracellular signal-regulated kinase
/ Fibrosis
/ Gene Knockdown Techniques
/ Heart
/ Hypertrophy
/ Kinases
/ Laboratories
/ Mice, Inbred C57BL
/ Molecular modelling
/ Myocytes, Cardiac - drug effects
/ Myocytes, Cardiac - physiology
/ Oral administration
/ Original
/ Phosphorylation
/ Physiology
/ Proteins
/ Quinazolines - pharmacology
/ Quinazolines - therapeutic use
/ Rats
/ Receptor, Epidermal Growth Factor - antagonists & inhibitors
/ Receptor, Epidermal Growth Factor - genetics
/ Receptor, Epidermal Growth Factor - metabolism
/ Risk factors
/ Signal transduction
/ small‐molecule inhibitor
/ Src protein
/ Studies
/ Tyrphostins - pharmacology
/ Tyrphostins - therapeutic use
2016
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Novel EGFR inhibitors attenuate cardiac hypertrophy induced by angiotensin II
by
Peng, Kesong
, Liang, Guang
, Qian, Yuanyuan
, Wang, Jingying
, Tian, Xinqiao
, Skibba, Melissa
, Liu, Zhiguo
, Zou, Chunpeng
, Xu, Zheng
, Li, Xiaokun
in
AKT protein
/ Angiotensin
/ Angiotensin II
/ Animals
/ Atherosclerosis
/ Cancer therapies
/ cardiac hypertrophy
/ Cardiomegaly - chemically induced
/ Cardiomegaly - drug therapy
/ Cardiomyocytes
/ Cardiotonic Agents - pharmacology
/ Cardiotonic Agents - therapeutic use
/ Cardiovascular diseases
/ Cardiovascular system
/ Cell Line
/ Congestive heart failure
/ Coronary artery disease
/ c‐Src
/ Disease prevention
/ Drug Evaluation, Preclinical
/ Epidermal growth factor
/ Epidermal Growth Factor - physiology
/ epidermal growth factor receptor
/ Epidermal growth factor receptors
/ Experiments
/ Extracellular signal-regulated kinase
/ Fibrosis
/ Gene Knockdown Techniques
/ Heart
/ Hypertrophy
/ Kinases
/ Laboratories
/ Mice, Inbred C57BL
/ Molecular modelling
/ Myocytes, Cardiac - drug effects
/ Myocytes, Cardiac - physiology
/ Oral administration
/ Original
/ Phosphorylation
/ Physiology
/ Proteins
/ Quinazolines - pharmacology
/ Quinazolines - therapeutic use
/ Rats
/ Receptor, Epidermal Growth Factor - antagonists & inhibitors
/ Receptor, Epidermal Growth Factor - genetics
/ Receptor, Epidermal Growth Factor - metabolism
/ Risk factors
/ Signal transduction
/ small‐molecule inhibitor
/ Src protein
/ Studies
/ Tyrphostins - pharmacology
/ Tyrphostins - therapeutic use
2016
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Novel EGFR inhibitors attenuate cardiac hypertrophy induced by angiotensin II
Journal Article
Novel EGFR inhibitors attenuate cardiac hypertrophy induced by angiotensin II
2016
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Overview
Cardiac hypertrophy is an important risk factor for heart failure. Epidermal growth factor receptor (EGFR) has been found to play a role in the pathogenesis of various cardiovascular diseases. The aim of this current study was to examine the role of EGFR in angiotensin II (Ang II)‐induced cardiac hypertrophy and identify the underlying molecular mechanisms. In this study, we observed that both Ang II and EGF could increase the phospohorylation of EGFR and protein kinase B (AKT)/extracellular signal‐regulated kinase (ERK), and then induce cell hypertrophy in H9c2 cells. Both pharmacological inhibitors and genetic silencing significantly reduced Ang II‐induced EGFR signalling pathway activation, hypertrophic marker overexpression, and cell hypertrophy. In addition, our results showed that Ang II‐induced EGFR activation is mediated by c‐Src phosphorylation. In vivo, Ang II treatment significantly led to cardiac remodelling including cardiac hypertrophy, disorganization and fibrosis, accompanied by the activation of EGFR signalling pathway in the heart tissues, while all these molecular and pathological alterations were attenuated by the oral administration with EGFR inhibitors. In conclusion, the c‐Src‐dependent EGFR activation may play an important role in Ang II‐induced cardiac hypertrophy, and inhibition of EGFR by specific molecules may be an effective strategy for the treatment of Ang II‐associated cardiac diseases.
Publisher
John Wiley & Sons, Inc,John Wiley and Sons Inc
Subject
/ Animals
/ Cardiomegaly - chemically induced
/ Cardiotonic Agents - pharmacology
/ Cardiotonic Agents - therapeutic use
/ c‐Src
/ Drug Evaluation, Preclinical
/ Epidermal Growth Factor - physiology
/ epidermal growth factor receptor
/ Epidermal growth factor receptors
/ Extracellular signal-regulated kinase
/ Fibrosis
/ Heart
/ Kinases
/ Myocytes, Cardiac - drug effects
/ Myocytes, Cardiac - physiology
/ Original
/ Proteins
/ Quinazolines - therapeutic use
/ Rats
/ Receptor, Epidermal Growth Factor - antagonists & inhibitors
/ Receptor, Epidermal Growth Factor - genetics
/ Receptor, Epidermal Growth Factor - metabolism
/ Studies
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