Abstract:
:Hypertrophic cardiomyopathy (HCM) is a well-established risk factor for cardiovascular mortality worldwide. Although hypertrophy is traditionally regarded as an adaptive response to physiological or pathological stress, prolonged hypertrophy can lead to heart failure. Here we demonstrate that Prdm16 is dispensable for cardiac development. However, it is required in the adult heart to preserve mitochondrial function and inhibit hypertrophy with advanced age. Cardiac-specific deletion of Prdm16 results in cardiac hypertrophy, excessive ventricular fibrosis, mitochondrial dysfunction, and impaired metabolic flexibility, leading to heart failure. We demonstrate that Prdm16 and euchromatic histone-lysine N-methyltransferase factors (Ehmts) act together to reduce expression of fetal genes reactivated in pathological hypertrophy by inhibiting the functions of the pro-hypertrophic transcription factor Myc. Although young Prdm16 knockout mice show normal cardiac function, they are predisposed to develop heart failure in response to metabolic stress. Our study demonstrates that Prdm16 protects the heart against age-dependent cardiac hypertrophy and heart failure.
journal_name
Cell Repjournal_title
Cell reportsauthors
Cibi DM,Bi-Lin KW,Shekeran SG,Sandireddy R,Tee N,Singh A,Wu Y,Srinivasan DK,Kovalik JP,Ghosh S,Seale P,Singh MKdoi
10.1016/j.celrep.2020.108288subject
Has Abstractpub_date
2020-10-20 00:00:00pages
108288issue
3issn
2211-1247pii
S2211-1247(20)31277-8journal_volume
33pub_type
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