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CRTC2 function in cardiac myocytes (699.5)
Author(s) -
Lai Ngai,
Tang Eric,
Deng Samuel,
Tang Tong,
Lew Wilbur
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.699.5
Subject(s) - medicine , myocyte , pressure overload , muscle hypertrophy , endocrinology , cardiac function curve , activator (genetics) , microbiology and biotechnology , biology , receptor , cardiac hypertrophy , heart failure
CRTC2 (cAMP‐regulated transcription co‐activator 2) is a transcription co‐factor which integrates signaling pathways activated by β‐adrenergic receptor (βAR) and Ca 2+ in metabolism. In this study, we tested the hypothesis that increased CRTC2 expression in cardiac myocytes would be equivalent to sustained βAR and Ca 2+ signaling, and could have a deleterious effect on the function of cardiac myocytes. To our surprise, decreased CRTC2 protein content was found in pressure overloaded hearts. CRTC2 expression in isolated cardiac myocytes was associated with blunted αAR‐stimulated hypertrophic growth without affecting cell proliferation. Expression of CRTC2 also blocked re‐activation of the fetal gene program, and altered expression of critical regulators of cardiac hypertrophy. Furthermore, CRTC2 affected expression of factors which are pivotal for Ca 2+ handling and apoptosis. The effects of nuclear‐targeted CRTC2 [ntCRTC2; i.e. CRTC2(S171A)] was more profound than CRTC2 itself. Using the newly generated ntCRTC2 transgenic mice, we found that ntCRTC2 expression attenuated LV hypertrophy and dysfunction in vivo in pressure overload. These results demonstrate the functional importance of CRTC2 in cardiac hypertrophy and function.