Familial hypertrophic cardiomyopathy: functional variance among individual cardiomyocytes as a trigger of FHC-phenotype development

摘要: Familial hypertrophic cardiomyopathy (FHC) is the most frequent inherited cardiac disease. It has been related to numerous mutations in many sarcomeric and even some non-sarcomeric proteins. So far, however, no common mechanism identified by which different proteins trigger development of FHC phenotype. Here we show for MYH7 variance force pCa-relations from normal highly abnormal as a feature all studied, while direct functional effects FHC-mutations, e.g., on generation, ATPase or calcium sensitivity contractile system, can be quite different. The variation among individual M. soleus fibers FHC-patients accompanied large mutant vs. wildtype β-MyHC-mRNA. Preliminary results similar β-MyHC-mRNA cardiomyocytes. We discuss our previously proposed concept how β-MyHC possibly other may initiate an FHC-phenotype cardiomyocytes that structural distortions within myocardium, leading cellular myofibrillar disarray. In addition, activate stretch-sensitive signalling non-myocyte cells known induce remodelling with interstitial fibrosis hypertrophy. Such will have major implications therapeutic strategies prevent FHC-development, reducing imbalances inhibition their triggering paths initiating remodelling. Targeting increased decreased function would require selective targeting protein reduce imbalances.