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

被引:4
作者
Zhang, Mao [1 ,2 ]
Zhang, Junxia [1 ]
Zhang, Wenjia [3 ]
Hu, Qingmei [1 ]
Jin, Li [1 ]
Xie, Peng [1 ]
Zheng, Wen [1 ]
Shang, Haibao [1 ]
Zhang, Yan [1 ,3 ,4 ]
机构
[1] Peking Univ, Inst Mol Med, Coll Future Technol, State Key Lab Membrane Biol, Beijing, Peoples R China
[2] Stanford Univ, Sch Med, Stanford Cardiovasc Inst, Stanford, CA 94305 USA
[3] Peking Univ, Hlth Sci Ctr, Key Lab Mol Cardiovasc Sci, Sch Basic Med Sci,Inst Cardiovasc Sci,Minist Educ, Beijing, Peoples R China
[4] Beijing Key Lab Cardiovasc Receptors Res, Beijing, Peoples R China
基金
国家重点研发计划; 中国国家自然科学基金;
关键词
CaMKII; CaMKII-delta; 9; cardiomyocyte death; cardiomyopathy; heart failure; hypertrophy; PROTEIN-KINASE-II; CARDIAC-HYPERTROPHY; MYOCARDIAL ISCHEMIA/REPERFUSION; INHIBITION PROTECTS; CELL-DEATH; INDEPENDENT ACTIVATION; OXIDATIVE ACTIVATION; CAMKII INHIBITION; ER STRESS; DELTA-B;
D O I
10.3389/fcvm.2021.820416
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
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页数:11
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