Hypertrophic Cardiomyopathy, a Disease of Altered Cardiac Energetics

摘要: Hypertrophic cardiomyopathy (HCM) is a complex disease, the phenotypes of which are only partly explained by the biomechanical effects of individual genetic variants. At the cellular level, HCM sarcomeric mutations generally enhance maximal force production ultimately leading to higher energy demands. Despite significant advances in elucidating sarcomeric structure-function relationships, there is limited knowledge on the link between altered cardiac energetics and HCM phenotypes. In this work, we test the hypothesis that changes in cardiac energetics are a common pathway leading to the clinical pathophysiological phenotypes of HCM. We performed a comprehensive multi-omic study of the molecular, ultrastructural, and functional features of HCM energetics using septal myectomy samples from 27 HCM patients and 13 normal controls (donor hearts). Combined mass spectrometry and RNA-Seq revealed …