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J Mol Cell Cardiol. 2011 Oct;51(4):548-53. doi: 10.1016/j.yjmcc.2010.12.004. Epub 2010 Dec 13.

Targeting AMPK for cardiac protection: opportunities and challenges.

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Mitochondria and Metabolism Center, Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA.


AMP-activated protein kinase (AMPK) regulates cellular energy homeostasis and multiple biological processes in cell growth and survival, hence an attractive drug target. AMPK is a heterotrimeric protein consisting of α catalytic, β and γ regulatory subunits; two isoforms of each subunit are present in the heart. Studies using both genetic and pharmacological approaches have demonstrated important roles of AMPK in protecting the heart during ischemia/reperfusion injury as well as in pathological hypertrophy and failure. There is also emerging evidence suggesting isoform-specific function of AMPK, e.g. mutations of the γ2 subunit cause human cardiomyopathy. Thus, strategies avoiding the undesirable effects of altering γ2-AMPK activity, such as isoform selective activation of AMPK may lead to cardioprotective therapies with greater efficacy and safety. This article is part of a special issue entitled "Key Signaling Molecules in Hypertrophy and Heart Failure."

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