Inducible re-expression of HEXIM1 causes physiological cardiac hypertrophy in the adult mouse.

Cardiovascular research 2013 Jul 01

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The transcription factor hexamethylene-bis-acetamide-inducible protein 1 (HEXIM1) regulates myocardial vascularization and growth during cardiogenesis. Our aim was to determine whether HEXIM1 also has a beneficial role in modulating vascularization, myocardial growth, and function within the adult heart. To achieve our objective, we created and investigated a mouse line wherein HEXIM1 was re-expressed in adult cardiomyocytes to levels found in the foetal heart. Our findings support a beneficial role for HEXIM1 through increased vascularization, myocardial growth, and increased ejection fraction within the adult heart. HEXIM1 re-expression induces angiogenesis, that is, essential for physiological hypertrophy and maintenance of cardiac function. The ability of HEXIM1 to co-ordinate processes associated with physiological hypertrophy may be attributed to HEXIM1 regulation of other transcription factors (HIF-1-α, c-Myc, GATA4, and PPAR-α) that, in turn, control many genes involved in myocardial vascularization, growth, and metabolism. Moreover, the mechanism for HEXIM1-induced physiological hypertrophy appears to be distinct from that involving the PI3K/AKT pathway. HEXIM1 re-expression results in the induction of angiogenesis that allows for the co-ordination of tissue growth and angiogenesis during physiological hypertrophy.

Citation

Monica M Montano, Candida L Desjardins, Yong Qui Doughman, Yee-Hsee Hsieh, Yanduan Hu, Heather M Bensinger, Connie Wang, Julian E Stelzer, Thomas E Dick, Brian D Hoit, Margaret P Chandler, Xin Yu, Michiko Watanabe. Inducible re-expression of HEXIM1 causes physiological cardiac hypertrophy in the adult mouse. Cardiovascular research. 2013 Jul 01;99(1):74-82