Adrenergic receptor blockade-induced regression of pressure-overload cardiac hypertrophy is associated with inhibition of the calcineurin/NFAT3/GATA4 pathway

  • Authors:
    • Dachun Yang
    • Shuangtao Ma
    • Yan Tan
    • De Li
    • Bing Tang
    • Jinsong Chen
    • Xiaohua Su
    • Gang Li
    • Xin Zhang
    • Yongjian Yang
  • Corresponding author:
  • View Affiliations

  • Published online on: Saturday, May 1, 2010
  • Pages: 497-501 DOI: 10.3892/mmr_00000287

Abstract

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.
Journal Cover

May 2010
Volume 3 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

2013 Impact Factor: 1.484
2014 I.F. (Expected) ≥ 1.757 Ranked #59/122 Medicine Research and Experimental
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APA
Yang, D., Ma, S., Tan, Y., Li, D., Tang, B., Chen, J. ... Yang, Y. (2010). Adrenergic receptor blockade-induced regression of pressure-overload cardiac hypertrophy is associated with inhibition of the calcineurin/NFAT3/GATA4 pathway. Molecular Medicine Reports, 3, 497-501. http://dx.doi.org/10.3892/mmr_00000287
MLA
Yang, D., Ma, S., Tan, Y., Li, D., Tang, B., Chen, J., Su, X., Li, G., Zhang, X., Yang, Y."Adrenergic receptor blockade-induced regression of pressure-overload cardiac hypertrophy is associated with inhibition of the calcineurin/NFAT3/GATA4 pathway". Molecular Medicine Reports 3.3 (2010): 497-501.
Chicago
Yang, D., Ma, S., Tan, Y., Li, D., Tang, B., Chen, J., Su, X., Li, G., Zhang, X., Yang, Y."Adrenergic receptor blockade-induced regression of pressure-overload cardiac hypertrophy is associated with inhibition of the calcineurin/NFAT3/GATA4 pathway". Molecular Medicine Reports 3, no. 3 (2010): 497-501. http://dx.doi.org/10.3892/mmr_00000287