CaMKII-δ9 Induces Cardiomyocyte Death to Promote Cardiomyopathy and Heart Failure

Heart failure is a syndrome in which the heart cannot pump enough blood to meet the body's needs, resulting from impaired ventricular filling or ejection of blood. Heart failure is still a global public health problem and remains a substantial unmet medical need. Therefore, it is crucial to identify new therapeutic targets for heart failure. Ca2+/calmodulin-dependent kinase II (CaMKII) is a serine/threonine protein kinase that modulates various cardiac diseases. CaMKII-delta 9 is the most abundant CaMKII-delta splice variant in the human heart and acts as a central mediator of DNA damage and cell death in cardiomyocytes. Here, we proved that CaMKII-delta 9 mediated cardiomyocyte death promotes cardiomyopathy and heart failure. However, CaMKII-delta 9 did not directly regulate cardiac hypertrophy. Furthermore, we also showed that CaMKII-delta 9 induced cell death in adult cardiomyocytes through impairing the UBE2T/DNA repair signaling. Finally, we demonstrated no gender difference in the expression of CaMKII-delta 9 in the hearts, together with its related cardiac pathology. These findings deepen our understanding of the role of CaMKII-delta 9 in cardiac pathology and provide new insights into the mechanisms and therapy of heart failure.

Automated summary

A study found that CaMKII-delta9-mediated cardiomyocyte death is a promoting factor in the development of cardiomyopathy and heart failure, but it does not directly regulate cardiac hypertrophy. Furthermore, CaMKII-delta9 induces cell death in adult cardiomyocytes by impairing the UBE2T/DNA repair signaling pathway. The study also revealed no gender difference in the expression of CaMKII-delta9 in the hearts.