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Adrenergic receptor blockade-induced regression of pressure-overload cardiac hypertrophy is associated with inhibition of the calcineurin/NFAT3/GATA4 pathway.
MedLine Citation:
PMID:  21472269     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Abstract/OtherAbstract:
Calcineurin and its downstream effectors nuclear factor of activated T-cells 3 (NFAT3) and zinc finger-containing transcription factor (GATA4) have been implicated in the development of cardiac hypertrophy. The aims of the present study were to investigate alterations in the calcineurin/NFAT3/GATA4 pathway in pressure-overload hypertrophy, and to determine whether adrenergic receptor blockade affects this signaling pathway. In aorta-banded rats compared with sham-operated rats, a significant increase in the phosphorylation levels of calcineurin and GATA4 was observed (both p<0.05), while the NFAT3 phosphorylation level was markedly decreased (p<0.05). Oral administration of either the non-selective β blocker/α-1 blocker carvedilol or the selective β-1 blocker metoprolol, but not the selective α-1 blocker terazosin, significantly suppressed the activated calcineurin/NFAT3/GATA4 pathway (all p<0.05) in addition to inducing a regression of cardiac hypertrophy. Pressure overload-induced up-regulation of c-myc was markedly attenuated by treatment with either carvedilol or metoprolol (both p<0.05). The present findings may expand our understanding of the correlation between sympathetic activity and the calcineurin/NFAT3/GATA4 pathway, and highlight these signal transducers as effective targets in the management of pressure overload-induced cardiac hypertrophy.
Authors:
Dachun Yang; Shuangtao Ma; Yan Tan; De Li; Bing Tang; Jinsong Chen; Xiaohua Su; Gang Li; Xin Zhang; Yongjian Yang
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Molecular medicine reports     Volume:  3     ISSN:  1791-3004     ISO Abbreviation:  Mol Med Rep     Publication Date:    2010 May-Jun
Date Detail:
Created Date:  2011-04-07     Completed Date:  2012-10-02     Revised Date:  2013-02-22    
Medline Journal Info:
Nlm Unique ID:  101475259     Medline TA:  Mol Med Rep     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  497-501     Citation Subset:  -    
Affiliation:
Department of Cardiology, General Hospital of PLA Chengdu Military Area Command, Chengdu, Sichuan 610083, P.R. China.
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