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Novel EGFR inhibitors attenuate Ang II‐induced cardiac hypertrophy (794.3)
Author(s) -
Peng Kesong,
Pan Yong,
Liang Guang
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.794.3
Subject(s) - muscle hypertrophy , medicine , protein kinase b , phosphorylation , heart failure , cardiac hypertrophy , mapk/erk pathway , pharmacology , egfr inhibitors , stimulation , endocrinology , in vivo , angiotensin ii , cancer research , epidermal growth factor receptor , chemistry , cancer , receptor , biology , biochemistry , microbiology and biotechnology
Background: Cardiac hypertrophy is a multiple response to physiological and pathological stimuli and an important risk factor for heart failure. The aim of this current study was to examine the effect of EGFR inhibitors on Ang II‐induced cardiac hypertrophy and further identify the underlying cellular/molecular mechanisms in Ang II/EGFR‐involved cardiac hypertrophy pathway. Methods: In vitro cultured rat H9C2 cells were induced hypertrophy by AngII. C57BL/6 mice were given a subcutaneous injection of AngII for two weeks and simultaneously were treated with EGFR inhibitors by daily gavage. Result: Stimulation of either Ang II or EGF significantly activated EGFR pathway and increased EGFR, AKT and ERK phosphorylation, while these increases were dose‐dependently inhibited by EGFR inhibitors. In the meantime, EGFR inhibitors attenuated Ang II‐mediated cardiac hypertrophy. Oral administration with small molecule EGFR inhibitors also decreased the cardiac hypertrophy and dysfuncti on in Ang II‐treated mice. Finally, the results showed that Ang II‐induced EGFR activation was mediated by Src phosphorylation. Conclusion: EGFR plays an important role in Ang II‐induced cardiac hypertrophy in vitro and in vivo, and inhibition of EGFR by specific molecules may be an effective strategy for the treatment of Ang II‐associated cardiac diseases. Grant Funding Source : China national science foundation