The role of AMPK in the control of cardiac hypertrophy

The development of cardiac hypertrophy in response to sustained cardiac stress causes considerable structural and metabolic remodeling of the heart that can have profound detrimental consequences. AMP-activated protein kinase (AMPK), a well-studied mediator of cellular energy homeostasis, has been shown to be a regulator of cardiac hypertrophy via its influence on several key signaling pathways involved in cardiomyocyte growth control. Although the ability of activated AMPK to inhibit protein synthesis has been a major focus of the anti-hypertrophic effects of AMPK, alterations in other cellular processes such as cardiac energy metabolism and cytoskeletal remodeling have also emerged as complimentary pathways by which AMPK is thought to inhibit the development of cardiac hypertrophy. Consistent with this, increasing evidence supports the use of pharmacological activators of AMPK to prevent the progression of cardiac hypertrophy. Despite these findings, this concept is not universally accepted as AMPK has also been shown to be elevated in hypertrophic hearts, suggesting that AMPK plays a role in promoting rather than inhibiting cardiomyocyte growth. This chapter reviews some of the published literature that focuses on the role of AMPK in the control of cardiomyocyte growth and discusses the potential benefits and pitfalls that may accompany the approach of pharmacologically activating AMPK to control the pathogenesis of cardiac hypertrophy.