The δA Isoform of Calmodulin Kinase II Mediates Pathological Cardiac Hypertrophy by Interfering with the HDAC4-MEF2 Signaling Pathway

Overview

Journal Biochem Biophys Res Commun

Publisher Elsevier

Specialty Biochemistry

Date 2011 May 11

PMID 21554860

Citations 15

Authors

Changlin Li

Xiangyu Cai

Haili Sun

Ting Bai

Xilong Zheng

Xing Wang Zhou

Xiongwen Chen

Donald L Gill

Jing Li

Xiang D Tang

Affiliations

Soon will be listed here.

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.

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