Targeting AMPK for cardiac protection: opportunities and challenges.

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."