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Over‐expression of a Corn Rac Gene Induces Cardiac Hypertrophy in Old Transgenic Mice: a Putative Role of Profilin1‐Induced Signaling
Author(s) -
Elnakish Mohammad T,
Hassona Mohamed D. H.,
Awad Mohamed M.,
Abouelnaga Zeinb A.,
Alhaj Mazin A.,
Kuppusamy Periannan,
Khan Mahmood,
Hassanain Hamdy H.
Publication year - 2011
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.25.1_supplement.951.2
Subject(s) - muscle hypertrophy , genetically modified mouse , transgene , small gtpase , medicine , signal transduction , endocrinology , biology , microbiology and biotechnology , gene , biochemistry
Rac1‐GTPase activation plays a key role in the initiation of cardiac hypertrophy linking NADPH oxidase/ROS to the hypertrophic signaling cascade. Therefore, we examined the effect of over‐expression of a constitutively active form of Zea maize Rac gene (ZmRacD) on the cardiac structure and function. Echocardiography and MRI analyses showed cardiac hypertrophy in old transgenic mice as evidenced by increased left ventricular (LV) mass and LV mass/body weight ratio. LV hypertrophy in the hearts of old transgenic mice was further confirmed by histopathology analysis. The cardiac structural and functional remolding of old transgenic mice were coupled with increased myocardial Rac‐GTPase activity (315%), ROS production (301.46%) and gp91phox expression (258%). There was also an increase in the STAT3 activity (213%), profilin1 expression (427%) and α1 (223.67%) β1 (239.6%) integrins expression. This led to the activation of the hypertrophic signaling pathways e.g. ERK1/2 (273.16%) and JNK (166.75%). Furthermore, there was an increase in the myocardial expression of PAK1 (257.51%). In conclusion, ZmRacD is a novel transgenic model that develops cardiac hypertrophy with age as a result of ZmRacD‐associated superoxide production. This led to the activation of STAT3 transcription factor that up‐regulates profilin1 expression that may contribute to the development of cardiac hypertrophy in this model.