Journal article

AMPK deficiency in cardiac muscle results in dilated cardiomyopathy in the absence of changes in energy metabolism

Miranda M Sung, Beshay N Zordoky, Adam L Bujak, James SV Lally, David Fung, Martin E Young, Sandrine Horman, Edward J Miller, Peter E Light, Bruce E Kemp, Gregory R Steinberg, Jason RB Dyck

Cardiovascular Research | OXFORD UNIV PRESS | Published : 2015

Abstract

AIMS: AMP-activated protein kinase (AMPK) is thought to be a central player in regulating myocardial metabolism and its activation has been shown to inhibit cardiac hypertrophy. Recently, mice with muscle-specific deletion of AMPK β1/β2 subunits (AMPKβ1β2-deficient mice, β1β2M-KO) have been generated and possess <10% of normal AMPK activity in muscle. However, how/if dramatic AMPK deficiency alters cardiac metabolism, function, or morphology has not been investigated. Therefore, the aim of this study was to determine whether a significant loss of AMPK activity alters cardiac function, metabolism, and hypertrophy, and whether this may play a role in the pathogenesis of heart failure. METHODS ..

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Grants

Awarded by NIH


Awarded by NATIONAL HEART, LUNG, AND BLOOD INSTITUTE


Funding Acknowledgements

This work was supported by grants from the Canadian Institute of Health Research to J.R.B.D. and G.R.S. B.E.K. and G.R.S. are supported by the National Health and Medical Research Council (NHMRC). B.E.K. is an NHMRC Fellow supported by the Australian Research Council and in part by the Victorian Government's Operational Infrastructure Support Program. G.R.S. is a Canada Research Chair in Metabolism and Obesity, and the J Bruce Duncan Chair in Metabolic Diseases. E.J.M. was supported by NIH grant HL109158. M.M.S. was supported by a fellowship from the Alberta Heart Failure Etiology and Research Team (HEART). B.N.Z. was supported by fellowships from Alberta Innovates-Health Solutions and the Canadian Institute of Health Research. D.F. was supported by a summer studentship from Alberta Innovates-Health Solutions.