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Development of dilated cardiomyopathy and impaired calcium homeostasis with cardiac-specific deletion of ESRRβ.

Rowe, GC; Asimaki, A; Graham, EL; Martin, KD; Margulies, KB; Das, S; Saffitz, J; Arany, Z (2017) Development of dilated cardiomyopathy and impaired calcium homeostasis with cardiac-specific deletion of ESRRβ. Am J Physiol Heart Circ Physiol, 312 (4). H662-H671. ISSN 1522-1539 https://doi.org/10.1152/ajpheart.00446.2016
SGUL Authors: Asimaki, Angeliki

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Abstract

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.

Item Type: Article
Additional Information: Copyright © 2017 the American Physiological Society
Keywords: calcium handling, dilated cardiomyopathy, estrogen-related receptor, Cardiovascular System & Hematology, 0606 Physiology, 1116 Medical Physiology
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: Am J Physiol Heart Circ Physiol
ISSN: 1522-1539
Language: eng
Dates:
DateEvent
1 April 2017Published
27 January 2017Published Online
23 January 2017Accepted
Publisher License: Publisher's own licence
Projects:
Project IDFunderFunder ID
K01 AR062128NIAMS NIH HHSUNSPECIFIED
P30 DK079626NIDDK NIH HHSUNSPECIFIED
P60 DK079626NIDDK NIH HHSUNSPECIFIED
R01 HL122547NHLBI NIH HHSUNSPECIFIED
PubMed ID: 28130335
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/108940
Publisher's version: https://doi.org/10.1152/ajpheart.00446.2016

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