Metoprolol Mitigates Ischemic Heart Remodeling and Fibrosis by Increasing the Expression of akap5 in Ischemic Heart

Background The purpose of this study was to verify whether metoprolol regulates AKAP5 expression and test the role of AKAP5 post-injury in mitigating cardiac infarction-associated tissue remodeling and fibrosis. Methods and results Sprague-Dawley (SD) rats underwent coronary artery ligation (CAL), which was followed immediately with metoprolol daily. HW/BW ratio and cardiac expression of COL1 and COL3 were increased in rats following CAL compared with shams. Treatment with metoprolol post-injury was associated with a decrease in HW/BW ratio and COL1/COL3 expression compared to uncontrol rats. CAL resulted in decreased cardiac AKAP5 expression compared to the control group, while metoprolol treatment restored levels compared to baseline shams. Cardiac expression levels of NFATc3/p-NFATc3 and GATA4 were modest at baseline and increased with injury, whereas metoprolol suppressed gene expression to below injury-associated changes. Immunoprecipitation indicated that AKAP5 could bind and regulate PP2B. Conclusions The results indicate that metoprolol mitigates ischemic cardia remodeling and fibrosis, which mechanism of mitigating remodeling likely to improve cardiac AKAP5 expression and AKAP5-PP2B interaction.