Long-term activation of adenosine monophosphate-activated protein kinase attenuates pressure-overload-induced cardiac hypertrophy

Hong Liang Li, Ran Yin, Dandan Chen, Dan Liu, Dong Wang, Qinglin Yang, Yu Gang Dong

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

Recent in vitro studies suggest that adenosine monophosphate (AMP)-activated protein kinase (AMPK) exerts inhibitory effects on cardiac hypertrophy. However, it is unclear whether long-term activation of AMPK will affect cardiac hypertrophy in vivo. In these reports, we investigate the in vivo effects of long-term AMPK activation on cardiac hypertrophy and the related molecular mechanisms. To examine the effects of AMPK activation in the development of pressure overload-induced cardiac hypertrophy, we administered 5-aminoimidazole 1 carboxamide ribonucleoside (AICAR, 0.5 mg/g body wt), a specific activator of AMPK, to rats with transaortic constriction (TAC) for 7 weeks. We found that long-term AMPK activation attenuated cardiac hypertrophy, and improved cardiac function in rats subjected to TAC. Furthermore, long-term AMPK activation attenuated protein synthesis, diminished calcineurin-nuclear factor of activated T cells (NFAT) and nuclear factor κB (NF-κB) signaling in pressure overload-induced hypertrophic hearts. Our in vitro experiments further proved that activation of AMPK by infection of AdAMPK blocked cardiac hypertrophy and NFAT, NF-κB, and MAPK signal pathways. The present study demonstrates for the first time that pharmacological activation of AMPK inhibits cardiac hypertrophy in through blocking signaling transduction pathways that are involved in cardiac growth. It presents a potential therapy strategy to inhibit pathological cardiac hypertrophy by increasing the activity of AMPK.

Original languageEnglish (US)
Pages (from-to)1086-1099
Number of pages14
JournalJournal of Cellular Biochemistry
Volume100
Issue number5
DOIs
StatePublished - Apr 1 2007

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AMP-Activated Protein Kinases
Cardiomegaly
Adenosine Monophosphate
Protein Kinases
Chemical activation
Pressure
NFATC Transcription Factors
TCF Transcription Factors
Constriction
Rats
Ribonucleosides
Calcineurin
Signal Transduction
Pharmacology

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Long-term activation of adenosine monophosphate-activated protein kinase attenuates pressure-overload-induced cardiac hypertrophy. / Li, Hong Liang; Yin, Ran; Chen, Dandan; Liu, Dan; Wang, Dong; Yang, Qinglin; Dong, Yu Gang.

In: Journal of Cellular Biochemistry, Vol. 100, No. 5, 01.04.2007, p. 1086-1099.

Research output: Contribution to journalArticle

Li, Hong Liang ; Yin, Ran ; Chen, Dandan ; Liu, Dan ; Wang, Dong ; Yang, Qinglin ; Dong, Yu Gang. / Long-term activation of adenosine monophosphate-activated protein kinase attenuates pressure-overload-induced cardiac hypertrophy. In: Journal of Cellular Biochemistry. 2007 ; Vol. 100, No. 5. pp. 1086-1099.
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