TY - JOUR
AU - Xu, Yong
AB - Ischemic reperfusion (I/R) contributes to deleterious cardiac remodeling and heart failure. The deacetylase SIRT1 has been shown to protect the heart from I/R injury. We examined the mechanism whereby I/R injury represses SIRT1 transcription in the myocardium. There was accumulation of trimethylated histone H3K9 on the proximal SIRT1 promoter in the myocardium in mice following I/R injury and in cultured cardiomyocytes exposed to hypoxia–reoxygenation (H/R). In accordance, the H3K9 trimethyltransferase SUV39H1 bound to the SIRT1 promoter and repressed SIRT1 transcription. SUV39H1 expression was up-regulated in the myocardium in mice following I/R insults and in H/R-treated cardiomyocytes paralleling SIRT1 down-regulation. Silencing SUV39H1 expression or suppression of SUV39H1 activity erased H3K9Me3 from the SIRT1 promoter and normalized SIRT1 levels in cardiomyocytes. Meanwhile, SUV39H1 deficiency or inhibition attenuated I/R-induced infarction and improved heart function in mice likely through influencing ROS levels in a SIRT1-dependent manner. Therefore, our data uncover a novel mechanism for SIRT1 trans-repression during cardiac I/R injury and present SUV39H1 as a druggable target for the development of therapeutic strategies against ischemic heart disease.
TI - SUV39H1 mediated SIRT1 trans-repression contributes to cardiac ischemia–reperfusion injury
JF - Basic Research in Cardiology
DO - 10.1007/s00395-017-0608-3
DA - 2017-03-08
UR - https://www.deepdyve.com/lp/springer-journals/suv39h1-mediated-sirt1-trans-repression-contributes-to-cardiac-IAbJxaxIrF
SP - 1
EP - 14
VL - 112
IS - 3
DP - DeepDyve
ER -