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The study aimed to identify the hypertrophy pathways responsible for hypertrophic cardiomyopathy (HCM) to develop new therapeutics to prevent or halt the disease. The study involved a comprehensive multi-omic characterization of hypertrophy pathways in HCM patients undergoing surgical myectomy using RNA sequencing, mass spectrometry, and phosphoproteomic assessment. The results showed transcriptional dysregulation with downregulation of 10 hypertrophy pathways and upregulation of 7, mainly involving the RAS-MAPK signaling cascade. The proteomic analysis revealed widespread upregulation and activation of hypertrophy pathways, regardless of genotype, with counterregulatory downregulation of the same pathways. The study suggests that RAS-MAPK activation plays a crucial role in HCM hypertrophy.
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