Key Points
- This research aims to explore how different genetic variants in hypertrophic cardiomyopathy lead to similar changes in protein forms within the heart.
- Used top-down proteomics to analyze sarcomeric proteoforms in hypertrophic cardiomyopathy.
- Assessed alterations in protein profiles following septal myectomy in patients.
- Evaluated the effect of post-translational modifications and alternative splicing on myofilament proteins.
- Identified significant decreases in phosphorylation of key myofilament and Z-disk proteins (P<0.05).
- Found consistent sarcomeric proteoform alterations across patients with different HCM-causing mutations.
- Highlighted the cross-talk in post-translational modifications suggesting dysregulated protein kinase A pathways in HCM.
Structured PICO
PPopulationHypertrophic cardiomyopathy (HCM) patients undergoing septal myectomy (n=16)
OOutcomeSarcomeric proteoform profiles and alterationssurrogate
Severe hypertrophic cardiomyopathy coalesces at the proteoform level despite distinct genotypes, suggesting potential for broad-spectrum treatments.