Hypertrophic cardiomyopathy:a paradigm for myocardial energy depletion.
Genetic analysis of hypertrophic cardiomyopathy (HCM), a mendelian form of cardiac hypertrophy, indicates that the primary defect is in sarcomeric function. However, the initial proposal that depressed myocardial contraction leads to a 'compensatory' hypertrophy has proven inconsistent with laboratory and clinical evidence. Drawing on observations of mutant contractile protein function, together with mouse models and clinical studies, we propose that sarcomeric HCM mutations lead to inefficient ATP utilization. The suggestion that energy depletion underlies HCM is supported by the HCM-like phenotype found with mutations in a variety of metabolic genes. A central role for compromised energetics would also help explain the unresolved clinical observations of delayed onset and asymmetrical hypertrophy in HCM, and would have implications for therapy in HCM and, potentially, in more-common forms of cardiac hypertrophy and failure.
Ashrafian
Houman
H
Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Redwood
Charles
C
Blair
Edward
E
Watkins
Hugh
H
D000255:Adenosine Triphosphate / Q000378:metabolism; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics* / Q000378:metabolism; D004734:Energy Metabolism; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D009154:Mutation; D009206:Myocardium / Q000378:metabolism*
D005819:Genetic Markers; D000255:Adenosine Triphosphate