Hdac inhibition protects cardiomyocytes by modulating expression of opioid receptor and inducing pro-survival autophagy by inhibiting class I HDACs during cardiac ischemia/reperfusion

The 20th century sees a revolution of translational medicine. By combining the genetics and bimolecular studies, many new drugs have been developed to treat infection, hypertension, heart failure and cancer. The use of percutaneous coronary intervention reduced the mortality and morbidity of acute coronary syndrome dramatically. However, there is no standard therapy available that can mitigate cardiac reperfusion injury, which contribute to around half of the infarct size. Prior studies showed that the activation of opioid receptors (OPRs), which are G protein-coupled receptors, induces cardioprotection both in vitro and in vivo. The exact mechanism of this protection is not clear yet. In addition, an FDA approved Histone deacetylase inhibitors (HDACi), SAHA, reduces infarct size significantly in a rabbit ischemia/reperfusion (I/R) injury through autophagy when it is given at the time of the reperfusion. We will test whether opiate receptors protect myocardium through activating autophagy and whether HDAC inhibition regulates opiate receptor expressions.