| First Author | Rowe GC | Year | 2017 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 312 |
| Issue | 4 | Pages | H662-H671 |
| PubMed ID | 28130335 | Mgi Jnum | J:241078 |
| Mgi Id | MGI:5897705 | Doi | 10.1152/ajpheart.00446.2016 |
| Citation | Rowe GC, et al. (2017) Development of dilated cardiomyopathy and impaired calcium homeostasis with cardiac-specific deletion of ESRRbeta. Am J Physiol Heart Circ Physiol 312(4):H662-H671 |
| abstractText | Mechanisms underlying the development of idiopathic dilated cardiomyopathy (DCM) remain poorly understood. Using transcription factor expression profiling, we identified estrogen-related receptor-beta (ESRRbeta), 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 ESRRbeta (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 ESRRbeta 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 ESRRbeta is a critical component in the onset of DCM by affecting contractility and calcium balance.NEW & NOTEWORTHY Estrogen-related receptor-beta (ESRRbeta) is highly expressed in the heart and cardiac-specific deletion results in the development of a dilated cardiomyopathy (DCM). ESRRbeta is mislocalized in human myocardium samples with DCM, suggesting a possible role for ESRRbeta in the pathogenesis of DCM in humans. |
