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Reinstallation of Glucocorticoid Receptor (GR) in the Heart Rescues Left Ventricular Systolic Function of Cardiac GR Knockout mice
Author(s) -
He Bo,
Oakley Robert H.,
Myers Page H,
Cidlowski John A
Publication year - 2017
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.31.1_supplement.687.17
Subject(s) - ejection fraction , glucocorticoid receptor , medicine , knockout mouse , cardiac function curve , endocrinology , heart failure , glucocorticoid , receptor , systole , biology , cardiology , diastole , blood pressure
Glucocorticoidsare primary stress hormones necessary for life. In recent years, stress isincreasingly associated with cardiovasculardiseases. We have previously demonstrated that adeficiencyin glucocorticoid receptor (GR) signaling in cardiomyocytes resulted in cardiachypertrophy, left ventricular (LV) systolic dysfunction, and heart failure. This suggested a crucial role for cardiomyocyte GR signaling in the function of the heart. In order to rescue the phenotypes of cardiomyocyte‐specific GR Knockout mice (cardioGRKO), we recently created an Adeno‐Associated Virus (AAV) to express mouse GR under the control of the cardiac‐specific troponin T(TnT) promoter to achieve cardiomyocytes‐specific GR expression (AAV‐GFP was used as a control). Our approach successfully achieved GR expression in the heart of 1‐month‐old CardioGRKO mice. We found that reinstallation of GR by AAV‐mediated gene transfer in cardiomyocytes completely rescued cardiovascular function in CardioGRKO mice. Specifically, ejection fraction (EF) and fractional shortening (FS) are significantly increased in the CardioGRKO treated with AAV‐mGRα compared to vector backbone (AAV‐GFP)‐treated control, suggesting the improvement of systolic function. In addition, left ventricular end‐systolic dimension (LVESD) and volume in systole (LV VolS) are significantly increased and restored to normal level compared to wild‐type controls. Further studies will be focused on the gene expression changes in genome wide expression analysis. In summary, the AAV‐mediated gene delivery system has allowed us to reinstall mGRα in cardioGRKO heart and thus to study the significance of GR signaling in heart diseases. Support or Funding Information NIH