Published online before print October 6, 2008, doi: 10.1161/HYPERTENSIONAHA.108.121244
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(Hypertension. 2008;52:813.)
© 2008 American Heart Association, Inc.
Editorial Commentaries |
AMP Activated Protein Kinase 2 Protection During Hypertension-Induced Hypertrophy
A Common Mediator in the Signaling Crossroads
From the Division of Cardiology, Department of Medicine, University of Texas Health Science Center, San Antonio.
Correspondence to Merry L. Lindsey, Medicine/Cardiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229-3900. E-mail lindseym@uthscsa.edu
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Hypertension-induced pressure overload causes concentric left ventricular hypertrophy, which may induce arrhythmias or ultimately lead to congestive heart failure.1 Indeed, hypertension is a leading cause of heart failure in the United States.2 The cardiac response to pressure loading involves the intersection of multiple hypertrophic and metabolic signaling pathways. In cardiac myocytes, the major energy sensor is AMP activated protein kinase (AMPK), which is activated by increased ratios of AMP to ATP to turn off protein synthesis and to turn on the energy conservation mode. In this issue of Hypertension, Zhang et al3 examine the role of AMPK
2 in mediating cardiac hypertrophy. Using AMPK2 null mice, they demonstrate that pressure overload (induced by 3 weeks of transverse aortic constriction) amplified the hypertrophic and fibrotic responses and further depressed cardiac function when compared with wild-type controls.
Although AMPK is ubiquitously expressed, concentrations of it are highest in skeletal and cardiac muscle. In cardiac myocytes, AMPK2 is the dominant catalytic subunit that complexes with 2 regulatory subunits (β and 
) to form the AMPK trimer. AMPK regulates fatty acid synthesis by phosphorylation of acetyl coenzyme A carboxylase to block malonyl-coenzyme A production. In addition, AMPK acts as a metabolic stress sensor in response to factors that limit fuel source, including hypoxia. Previous work has shown the following: (1) AMPK activity increases in pressure overload hypertrophy4; (2) long-term activation of AMPK attenuates cardiac hypertrophy induced by aortic banding5; (3) AMPK activation inhibits protein synthesis and hypertrophy in vitro
Related Article:
2 Deficiency Exacerbates Pressure-Overload–Induced Left Ventricular Hypertrophy and Dysfunction in Mice
Hypertension 2008 52: 918-924.