Key result
Cardiac-specific deletion of ESRRβ in mice led to dilated cardiomyopathy and sudden death at ~10 months, and ESRRβ was found to be mislocalized in human myocardium samples with DCM.
ESRRβ plays a critical role in the pathogenesis of dilated cardiomyopathy by regulating cardiomyocyte contractility and calcium balance.
ESRRβ deletion precipitates DCM and sudden death in mice; hypothesis-generating for its role in human cardiomyopathy.
Mechanisms underlying the development of idiopathic dilated cardiomyopathy (DCM) remain poorly understood. Using transcription factor expression profiling, we identified estrogen-related receptor-β (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 DCM and sudden death at ~10 mo 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 DCM by affecting contractility and calcium balance. NEW & NOTEWORTHY Estrogen-related receptor-β (ESRRβ) is highly expressed in the heart and cardiac-specific deletion results in the development of a dilated cardiomyopathy (DCM). ESRRβ is mislocalized in human myocardium samples with DCM, suggesting a possible role for ESRRβ in the pathogenesis of DCM in humans.
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Rowe et al. (2017) studied Idiopathic dilated cardiomyopathy (DCM). Cardiac-specific deletion of ESRRβ vs. Wild-type / other cardiomyopathies was evaluated on Development of dilated cardiomyopathy and sudden death. Cardiac-specific deletion of ESRRβ in mice led to dilated cardiomyopathy and sudden death at ~10 months, and ESRRβ was found to be mislocalized in human myocardium samples with DCM.
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