The molecular landscape of hypertrophic cardiomyopathy across disease stages and genotypes.

Single-nucleus RNA sequencing reveals genotype-specific cellular remodeling in hypertrophic cardiomyopathy across disease stages, with a 20-fold increase in proarrhythmogenic cardiomyocyte states.

• Why it matters: Understanding the molecular and cellular mechanisms underlying HCM progression and genotype differences is crucial for developing targeted therapies and improving patient outcomes, as current knowledge gaps hinder personalized treatment.
• What they did: Researchers analyzed cardiac tissues from 47 HCM patients at various stages using single-nucleus RNA sequencing, identifying transcriptional programs linked to hypertrophy, fibrosis, and vascular changes, and validated key genes like PRR16.
• The result: Findings highlight widespread genotype-driven remodeling, including cardiomyocyte hypertrophy, fibrosis, and microvascular dysfunction, enabling improved prediction of disease progression and potential therapeutic targets.