Mechanisms underlying the development of Idiopathic Dilated Cardiomyopathy (DCM) remain poorly understood. Using transcription factor expression profiling, we identified estrogen-related receptor beta (ESRRβ), a member of the nuclear receptor family of transcription factors, as highly expressed in murine hearts and other highly oxidative striated muscle beds. Mice bearing cardiac-specific deletion of ESRRβ (MHC-ERRB KO) develop dilated cardiomyopathy and sudden death at approximately 10 months of age. Isolated adult cardiomyocytes from the MHC-ERRB KO mice showed an increase in calcium sensitivity and impaired cardiomyocyte contractility, which preceded echocardiographic cardiac remodeling and dysfunction by several months. Histological analyses of myocardial biopsies from patients with various cardiomyopathies revealed that ESRRβ protein is absent from the nucleus of cardiomyocytes from patients with DCM, but not other forms of cardiomyopathy (ischemic, hypertrophic and arrhythmogenic right ventricular cardiomyopathy). Taken together these observations suggest that ESRRβ is a critical component in the onset of dilated cardiomyopathy by affecting contractility and calcium balance.
- estrogen-related receptor
- dilated cardiomyopathy
- calcium handling
- Copyright © 2016, American Journal of Physiology-Heart and Circulatory Physiology