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Inducible reexpression of HEXIM1 activates physiological rather than pathological responses in the adult heart
Author(s) -
Watanabe Michiko,
Doughman Yong Qui,
Desjardins Candida,
Hu Yanduan,
Wang Connie,
Hoit Brian,
Chandler Margaret,
Yu Xin,
Montano Monica
Publication year - 2012
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.26.1_supplement.526.2
Subject(s) - angiogenesis , cancer research , pathological , cardioprotection , transcription factor , medicine , biology , microbiology and biotechnology , endocrinology , gene , ischemia , biochemistry
The transcription factor Hexamethylene‐bis‐acetamide‐inducible protein 1 (HEXIM1) is a tumor suppressor and cyclin‐dependent kinase inhibitor that we and others have shown to be critical for cardiovascular development. To examine its function in the adult heart, we created and investigated a mouse line wherein HEXIM1 reexpression was induced in adult cardiomyocytes. These mouse hearts exhibited morphology, physiology, and gene expression resembling hearts that have undergone a physiological rather than a pathological response. We also discovered mechanistic aspects of HEXIM1 that may explain effects of HEXIM1 induction in adult hearts. HEXIM1 binds to and stabilizes Hypoxia Inducible Factor‐1 [alpha] that controls many genes involved in vasculogenesis and metabolism. This role of HEXIM1 may result in induction of angiogenesis essential for physiological hypertrophy and maintenance of cardiac function under stress. Thus, HEXIM1 plays a critical regulatory role in coordinating responses of the adult heart to stress and its reexpression in the adult may be useful in cardioprotection therapy. This project was supported by NIH R01 CA92440 & AHA 0855543D (MMM), ARRA NIH R01 HL091171 (MW), NIH R01s HL73315 & HL86935 (X.Y.)