Article Impact Level: HIGH Data Quality: STRONG Summary of Nature Cardiovascular Research, https://doi.org/10.1038/s44161-025-00721-2 Dr. Jonathan S. Achter et al.
Points
- The study developed a method for quantitative proteomics using formalin-fixed, paraffin-embedded cardiac specimens.
- Proteomic profiles in FFPE human heart tissue were well-preserved, allowing high-resolution quantitative analysis.
- Approximately 4,000 proteins were quantified per sample, effectively distinguishing disease states and subanatomical regions.
- The human sinoatrial node showed enrichment of collagen VI and G protein-coupled receptor signaling.
- Myocardial biopsies from arrhythmogenic cardiomyopathy patients exhibited fibrosis and metabolic/cytoskeletal derangements, differing from donor hearts.
Summary
This study demonstrates a robust method for quantitative proteomics of formalin-fixed, paraffin-embedded (FFPE) cardiac specimens, addressing the long-standing challenge of tissue accessibility in translational cardiac research. FFPE heart tissue, which is extensively preserved in pathology archives globally, represents a vast, underutilized resource for molecular profiling. The research confirmed that proteomic profiles within these archived human heart specimens are remarkably well-preserved and amenable to high-resolution, quantitative analysis, thus overcoming a significant technical barrier.
The methodology allowed for the quantification of approximately 4,000 proteins per sample. This comprehensive protein profiling effectively distinguished between various disease states and specific subanatomical regions within the heart, revealing distinct underlying protein signatures. For instance, the human sinoatrial node exhibited a notable enrichment of collagen VI and proteins associated with G protein-coupled receptor signaling, highlighting its specialized cellular composition.
Furthermore, the proteomic analysis of myocardial biopsies from patients diagnosed with arrhythmogenic cardiomyopathy showed clear characteristics of fibrosis and significant metabolic/cytoskeletal derangements. These findings distinctly separated them from donor heart biopsies, providing molecular insights into disease pathogenesis. This study conclusively establishes FFPE heart tissue as a robust and scalable resource for cardiac proteomics, paving the way for large-scale retrospective molecular profiling and accelerating disease discovery and precision cardiology initiatives using previously inaccessible archived specimens.
Link to the article: https://www.nature.com/articles/s44161-025-00721-2
References
Achter, J. S., Jensen, T. H. L., Pisano, P., Bundgaard, J. S., Raaschou-Oddershede, D., Rossing, K., Wierer, M., & Lundby, A. (2025). Quantitative proteomics of formalin-fixed, paraffin-embedded cardiac specimens uncovers protein signatures of specialized regions and patient groups. Nature Cardiovascular Research, 1–15. https://doi.org/10.1038/s44161-025-00721-2
