Abstract 20587: Myocyte-Specific Over-Expression of Hdac4 Promotes Myocardial Ischemia and Reperfusion Injury
Background: Histone deacetylases (HDACs) have been recently demonstrated to play a critical role in modulating myocardial protection and cardiomyocyte survival. However, the specific HDAC in mediating myocardial ischemia/reperfusion injury is currently unknown.
Objective: The goal of this study is sought to define whether cardiac specific over-expression of HDAC4 would exacerbate myocardial ischemia and reperfusion injury.
Methods: We created myocyte-specific HDAC4 transgenic mice, in which cDNA encoding HDAC4 was cloned into an expression vector encoding alpha-myosine heavy chain (the α-MHC promoter). Langendorff isovolumetrically perfused hearts from wild type (WT) control (n=5) and α-MHC-HDAC4 mice (n=5) were subjected to 30 minutes of ischemia followed by 30 minutes of reperfusion. Infarct size was measured by triphenyl tetrazolium chloride staining. HDAC4 protein and activity in myocardium were determined.
Results: The HDAC4 protein levels in the hearts of α-MHC-HDAC4 mice were significantly higher than those of control wild type. HDAC activity was elevated in MHC-HDAC4 mice as compared with wild type mice. In adult mice, there was no significant difference in the heart weight-body weight ratio between α-MHC-HDAC and wild-type mice. As compared to wild type mice, myocyte-specific over-expression of HDAC4 resulted in an elevation of left ventricular end-diastolic pressure (LVEDP) and reduction in the recovery of rate and pressure products (RPP) at the end of reperfusion. Furthermore, over-expression of HDAC4 increased myocardial infarct size as compared to wild type mice.
Conclusions: These findings indicate that specific over-expression of HDAC4 exacerbates myocardial ischemia and reperfusion injury.
Author Disclosures: L. Zhang: None. J. Du: None. Y. Zhao: None. T.C. Zhao: None.
This research has received full or partial funding support from the American Heart Association.
- © 2014 by American Heart Association, Inc.