Role of non-myocytes activation in pathogenesis of hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a common, serious, genetic heart muscle disorder. The biophysical mechanisms by which HCM mutations in sarcomeric proteins disrupt cardiomyocyte function are largely understood, but the cellular and molecular pathways leading to the complex, variable and adverse remodelling of the non-myocyte compartment are unexplained. We reported infiltrative immune cells and inflammatory responses in individuals with HCM using imaging and single nucleus RNA seq data. We found a similar response in a translationally faithful mouse model (i.e., Actc1[E99K]), which recapitulates features in HCM patients carrying the same mutation. A longitudinal study was performed to characterise temporal changes in cardiac and immune phenotyping. Bulk heart tissue RNA seq was part of the characterisation of enriched inflammatory gene signatures in HCM.