Metabolic perturbations in the pathogenesis of hypertrophic cardiomyopathy
Ashrafian H., Watkins H.
Hypertrophic cardiomyopathy (HCM) has been informative as a genetic model of cardiac hypertrophy. Unexpectedly, analysis of the diverse sarcomeric mutations that typically cause HCM has implicated energetic compromise in pathogenesis. Mutations in a regulatory subunit of AMP-activated protein kinase (AMPK) also cause HCM, an effect mediated by glycogen accumulation leading to suppression of total AMPK activity and thus increased protein synthesis. These observations demonstrate the central role of energy homeostasis in cardiac growth and suggest important new treatment strategies. © 2005 Elsevier Ltd. All rights reserved.