Emerging Relationships of Sarcomeric Mutations and the Cardiomyocyte Transcriptome in the Setting of Familial Hypertrophic Cardiomyopathy
DOI:
https://doi.org/10.65539/s5hc6w24Keywords:
familial hypertrophic cardiomyopathy, sarcomeric mutations, MYH7, MYBPC3, cardiomyocyte transcriptomeAbstract
Familial hypertrophic cardiomyopathy (FHC) is the most common inherited cardiac disease and is largely driven by mutations in sarcomeric proteins, especially β-myosin heavy chain (MYH7) and myosin-binding protein C (MYBPC3). This review synthesizes emerging data on how these mutations alter cardiomyocyte mechanics and gene expression. MYH7 mutations reduce force generation and myofibrillar density, while MYBPC3 haploinsufficiency produces hypercontractile, energetically inefficient myocytes. Transcriptomic and microRNA profiling reveal early changes in stress-response, fibrosis, and electrical remodeling pathways. The article also highlights evolving therapies, including cardiac myosin inhibitors like mavacamten and experimental gene-editing approaches, that target upstream molecular drivers rather than downstream structural consequences.
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