Post-Transcriptional Regulation of alpha-1-Antichymotrypsin by miR-137 in Chronic Heart Failure and Mechanical Support

Purpose Better understanding of remodeling is a major objective of heart failure (HF) research to stop/reverse its progression. Left ventricular assist devices (LVADs) may lead to partial reverse remodeling. In this study, proteomics identified significant changes in alpha-1-antichymotrypsin (ACT) levels during LVAD support. The role of ACT in reverse remodeling was studied in detail. Methods and Materials Heart tissue (n=15) of patients with non-ischemic dilated cardiomyopathy was obtained during LVAD implantation (pre) and compared with heart tissue obtained after heart transplantation (post). Plasma was taken pre and 1, 3, and 6 months after implantation (n=18) and analyzed by ACT ELISA. Heart tissue was used to investigate the amount of ACT mRNA by q-PCR and localization of ACT by immunohistochemistry and in situ hybridization. Since evidence implicates that microRNAs (miRs) are involved in myocardial disease processes, we investigated whether ACT is post-transcriptional regulated by miRs. Results Expression of ACT mRNA (Q-PCR) decreased significantly in post-LVAD myocardial tissue compared to pre-LVAD tissue (p Conclusions High ACT plasma levels in HF normalized during LVAD support, which coincides with decreased ACT mRNA in heart tissue, while miR-137 levels increased. MiR-137 directly targeted ACT, thereby indicating that ACT and miR-137 play a role in reverse remodeling and are potential therapeutic targets for HF.