The harm of heart failure mainly causes patients to develop dyspnea, fatigue, fluid retention, and other symptoms, which impair patients’ activity tolerance and lead to a dramatic decrease in patients’ quality of life. The purpose of this study was to verify whether metoprolol regulates AKAP5 expression and test the role of AKAP5 postinjury in mitigating cardiac infarction-associated tissue remodeling and fibrosis. Sprague-Dawley (SD) rats underwent coronary artery ligation (CAL), which was followed immediately with metoprolol daily. And western blot and coimmunoprecipitation experiments were performed to detect the expression of related proteins in the sham-operated group, model group, and drug-treated group. HW/BW ratio and cardiac expression of COL1 and COL3 were increased in rats following CAL compared with shams. Treatment with metoprolol postinjury was associated with a decrease in HW/BW ratio and COL1/COL3 expression compared to uncontrolled 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. In summary, we know that metoprolol alleviates ischemic cardiac remodeling and fibrosis, and the mechanism of alleviating remodeling may improve cardiac AKAP5 expression and AKAP5-PP2B interaction.

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A-kinase anchoring protein (AKAP) 5 has a variety of biological activities. This study explored whether AKAP5 is involved in cardiomyocyte apoptosis induced by H/R and its possible mechanism. H9C2 cells were used to construct an H/R model in vitro, followed by overexpression of AKAP5 in the cells. Flow cytometry was used to detect the rate of cardiomyocyte apoptosis. The expression of phospholamban (PLN) phosphorylation, SERCA2a and apoptosis-related proteins were determined by western blot. Immunofluorescence staining and immunoprecipitation were used to detect the distribution of and interaction between AKAP5, PKA, and PLN. After H/R induction, H9C2 cells had significantly reduced expression of AKAP5 protein. Upregulation of AKAP5 promoted cell survival and significantly reduced LDH level and apoptosis rate of H9C2 cells. In addition, the overexpression of AKAP5 was accompanied by the activation of the PLN/SERCA2a signaling pathway and a reduction in apoptosis. Immunofluorescence staining and immunoprecipitation revealed that AKAP5 colocalized and interacted with PLN and PKA.Interestingly,St-Ht31 inhibited the effect of AKAP5 overexpression on H/R-induced apoptosis in H9C2 cardiomyocytes. AKAP5 overexpression alleviated H/R-induced cardiomyocyte apoptosis, possibly through anchoring to PKA to mediate the PLN/SERCA pathway, suggesting that AKAP5 is a potential therapeutic target for the prevention and treatment of ischemia-reperfusion injury.