title: The δA isoform of calmodulin kinase II mediates pathological cardiac hypertrophy by interfering with the HDAC4-MEF2 signaling pathway.
abstract: Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is a new promising target for prevention and treatment of cardiac hypertrophy and heart failure. There are three δ isoforms of CaMKII in the heart and previous studies focused primarily on δB and δC types. Here we report the δA isoform of CaMKII is also critically involved in cardiac hypertrophy. We found that δA was significantly upregulated in pathological cardiac hypertrophy in both neonatal and adult models. Upregulation of δA was accompanied by cell enlargement, sarcomere reorganization and reactivation of various hypertrophic cardiac genes including atrial natriuretic factor (ANF) and β-myocin heavy chain (β-MHC). Studies further indicated the pathological changes were largely blunted by silencing the δA gene and an underlying mechanism indicated selective interference with the HDAC4-MEF2 signaling pathway. These results provide new evidence for selective interfering cardiac hypertrophy and heart failure when CaMKII is considered as a therapeutic target.
authors.affiliation: Department of Pharmacology, Nankai University School of Medicine, Tianjin, China.
authors.forename: Changlin
authors.initials: C
authors.lastname: Li
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Cai
authors.forename: Haili
authors.initials: H
authors.lastname: Sun
authors.forename: Ting
authors.initials: T
authors.lastname: Bai
authors.forename: Xilong
authors.initials: X
authors.lastname: Zheng
authors.forename: Xing Wang
authors.initials: XW
authors.lastname: Zhou
authors.forename: Xiongwen
authors.initials: X
authors.lastname: Chen
authors.forename: Donald L
authors.initials: DL
authors.lastname: Gill
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Xiang D
authors.initials: XD
authors.lastname: Tang
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000096:biosynthesis* / Q000235:genetics; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020868:Gene Silencing; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D026161:MADS Domain Proteins / Q000378:metabolism*; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D007527:Isoenzymes; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; C578037:MEF2A protein, rat; D018006:Myogenic Regulatory Factors; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C517677:Camk2d protein, rat; C559944:HDAC4 protein, rat; D006655:Histone Deacetylases