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(Hypertension. 2008;52:918.)
© 2008 American Heart Association, Inc.

Original Articles

AMP Activated Protein Kinase-2 Deficiency Exacerbates Pressure-Overload–Induced Left Ventricular Hypertrophy and Dysfunction in Mice

Ping Zhang; Xinli Hu; Xin Xu; John Fassett; Guangshuo Zhu; Benoit Viollet; Wayne Xu; Brian Wiczer; David A. Bernlohr; Robert J. Bache; Yingjie Chen

From the Cardiovascular Division (P.Z., X.H., X.X., J.F., G.Z., R.J.B., Y.C.) and Center for Vascular Biology (X.H., X.X., G.Z., Y.C.), Department of Medicine, Supercomputing Institute (W.X.), and Department of Biochemistry, Molecular Biology, and Biophysics (B.W., D.A.B.), University of Minnesota, Minneapolis; and the Institut Cochin (B.V.), Université René Descartes, Centre National de la Recherche Scientifique (UMR 8104), Paris, France; and Institut National de la Santé et de la Recherche Medicale U567 (B.V.), Paris, France.

Correspondence to Yingjie Chen, University of Minnesota, Mayo Mail Code 508, 420 Delaware St SE, Minneapolis, MN 55455. E-mail chenx106{at}umn.edu

AMP activated protein kinase (AMPK) plays an important role in regulating myocardial metabolism and protein synthesis. Activation of AMPK attenuates hypertrophy in cultured cardiac myocytes, but the role of AMPK in regulating the development of myocardial hypertrophy in response to chronic pressure overload is not known. To test the hypothesis that AMPK2 protects the heart against systolic overload–induced ventricular hypertrophy and dysfunction, we studied the response of AMPK2 gene deficient (knockout [KO]) mice and wild-type mice subjected to 3 weeks of transverse aortic constriction (TAC). Although AMPK2 KO had no effect on ventricular structure or function under control conditions, AMPK2 KO significantly increased TAC-induced ventricular hypertrophy (ventricular mass increased 46% in wild-type mice compared with 65% in KO mice) while decreased left ventricular ejection fraction (ejection fraction decreased 14% in wild-type mice compared with a 43% decrease in KO mice). AMPK2 KO also significantly exacerbated the TAC-induced increases of atrial natriuretic peptide, myocardial fibrosis, and cardiac myocyte size. AMPK2 KO had no effect on total S6 ribosomal protein (S6), p70 S6 kinase, eukaryotic initiation factor 4E, and 4E binding protein-1 or their phosphorylation under basal conditions but significantly augmented the TAC-induced increases of p-p70 S6 kinase^Thr389, p-S6^Ser235, and p-eukaryotic initiation factor 4E^Ser209. AMPK2 KO also enhanced the TAC-induced increase of p-4E binding protein-1^Thr46 to a small degree and augmented the TAC-induced increase of p-Akt^Ser473. These data indicate that AMPK2 exerts a cardiac protective effect against pressure-overload–induced ventricular hypertrophy and dysfunction.

Key Words: hypertrophy • congestive heart failure • mTOR

Related Article:

AMP Activated Protein Kinase 2 Protection During Hypertension-Induced Hypertrophy: A Common Mediator in the Signaling Crossroads

Rogelio Zamilpa and Merry L. Lindsey
Hypertension 2008 52: 813-815. [Extract] [Full Text] [PDF]

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