Abstract
BackgroundHistone deacetylases (HDACs) play a critical role in modulating myocardial protection and cardiomyocyte survivals. However, Specific HDAC isoforms in mediating myocardial ischemia/reperfusion injury remain currently unknown.We used cardiomyocyte-specific overexpression of active HDAC4 to determine the functional role of activated HDAC4 in regulating myocardial ischemia and reperfusion in isovolumetric perfused hearts.MethodsIn this study, we created myocyte-specific active HDAC4 transgenic mice to examine the functional role of active HDAC4 in mediating myocardial I/R injury. Ventricular function was determined in the isovolumetric heart, and infarct size was determined using tetrazolium chloride staining.ResultsMyocyte-specific overexpressing activated HDAC4 in mice promoted myocardial I/R injury, as indicated by the increases in infarct size and reduction of ventricular functional recovery following I/R injury. Notably, active HDAC4 overexpression led to an increase in LC-3 and active caspase 3 and decrease in SOD-1 in myocardium. Delivery of chemical HDAC inhibitor attenuated the detrimental effects of active HDAC4 on I/R injury, revealing the pivotal role of active HDAC4 in response to myocardial I/R injury.ConclusionsTaken together, these findings are the first to define that activated HDAC4 as a crucial regulator for myocardial ischemia and reperfusion injury.
Highlights
Histone deacetylases (HDACs) play a critical role in modulating myocardial protection and cardiomyocyte survivals
Echocardiographic measurements show no differences in cardiac function as indicated by LVIDs, LVIDd, ejection fraction (EF), and fractional shortening (FS) at two-month of age between wild type and MHC-Histone deacetylase4 (HDAC4) mice (Fig. 2)
Salient findings In this study, we demonstrated that: 1) This is the first study to identify that overexpression of activated HDAC4, a major class II HDAC isoform in the heart exacerbates myocardial Ischemia and reperfusion injury (I/R) injury, as indicated by the increase in infarct size and the reduction of myocardial function; 2) Over-expression of HDAC4-induced I/R injury was attenuated by delivery of HDAC inhibitor, TSA; 3) activated HDAC4 promoted I/R injury was associated with increased in autophagy, apoptosis and decreased Superoxide dismutase-1 (SOD-1)
Summary
Histone deacetylases (HDACs) play a critical role in modulating myocardial protection and cardiomyocyte survivals. Specific HDAC isoforms in mediating myocardial ischemia/reperfusion injury remain currently unknown. We used cardiomyocyte-specific overexpression of active HDAC4 to determine the functional role of activated HDAC4 in regulating myocardial ischemia and reperfusion in isovolumetric perfused hearts. Histone deacetylases (HDACs) are a group of enzymes that regulate gene expression by the modulation of their interactions with chromatin through the deacetylation of histones. The acetylation and deacetylation of chromatin histones are considered to be critical in the regulation of transcription in in the biological responses. Histone deacetylase result in deacetylation and transcriptional repression (Turner 2000; McKinsey 2012). Class III HDACs were identified on the basis of sequence similarity with Sir, which includes SIRT1–7 and Sir
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
