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Cardiac Overexpression of Constitutive Active Form of Zea maize Rac‐D in Transgenic Mice Deteriorates Postischemic Contractile Recovery
Author(s) -
MoustafaBayoumi Moustafa,
Talukder Hassan,
Alhaj Mazin,
ElSayed Osama,
Abouelnaga Zenib,
Hassona Mohamed,
Zweier Jay,
GoldschmidtClermont Pascal,
Hassanain Hamdy
Publication year - 2008
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.22.1_supplement.730.19
Subject(s) - genetically modified mouse , transgene , in vivo , medicine , ischemia , endocrinology , chemistry , biology , gene , biochemistry , microbiology and biotechnology
The present study investigated the effect of increased reactive oxygen species (ROS) in the heart on myocardial injury. Our hypothesis is that transgenic mice overexpressing Rac 1 in the heart will have increased ROS generation and poor contractile recovery during ischemia reperfusion (I/R). We have generated a transgenic mouse model that expresses the cDNA of a constitutively active mutant of Zea maize Rac‐D gene in the heart of FVB/N mice using a mouse α‐myosin heavy chain promoter. IHC analysis confirmed the expression of Rac‐D protein in the heart of transgenic (TG) mice. Echocardiographic analysis showed significantly low ejection fraction in TG mice compared to control mice [20±4 (TG) vs. 62±5 (control), P <0.05]. I/R studies were performed in isolated hearts from age matched control and TG mice. Rac‐D TG mice demonstrated markedly poor post.ischemic contractile recovery [59±4% (TG) vs. 99±5% (control), P <0.001] with frequent abnormal ventricular rhythms compared to age matched control. These results suggest an important role of Rac 1 in NADPH‐ROS mediated myocardial injury during I/R. In conclusion, the Rac‐D transgenic animal model provides an advantage to investigate the signaling mechanisms regulating ischemic heart diseases. In addition, it is a unique model for in vivo studies utilizing novel therapeutic approaches targeting Rac 1 to reduce ischemic heart diseases.