Proteomic Characterisation of Heart Failure Reveals a Unique Molecular Phenotype for Hypertrophic Cardiomyopathy
Abstract
:1. Introduction
2. Materials and Methods
2.1. Sample Cohort
2.2. Sample Preparation
2.3. Mass Spectrometry Analysis
2.4. Data Analysis
3. Results
3.1. Proteomic Characterisation of Heart Failure
3.2. Differential Protein Expression between Heart Failure and Non-Failing Heart Tissue
3.3. Differential Protein Expression in Obstructive HCM Reveals Unique Pathology of Disease
3.4. Differential Protein Expression between Obstructive HCM and Other Heart Failure Subtypes
3.5. In Silico Validation of HCM-Associated Proteins
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Protein Name (Gene ID) | Median (NF, DCM, ISCM, oHCM) | p | p.adj | log2ratio | Clinical Correlations (r) | |
---|---|---|---|---|---|---|
Unique oHCM + validated | Apolipoprotein A-IV (APOA4) * | 1067.9 | 6.00 × 10−7 | 0.004 | 1.299 | |
N(G),N(G)-dimethylarginine dimethylaminohydrolase 1 (DDAH1) * | 132.4 | 4.00 × 10−5 | 0.027 | 1.116 | LVEDV: r = −0.9048, p = 0.0046 | |
LVEF: r = −0.7197, p = 0.0344 | ||||||
LVESV: r = 0.7167, p = 0.0369 | ||||||
Fructose-bisphosphate aldolase A (ALDOA) | 36,406.44 | 1.00 × 10−4 | 0.045 | −0.235 | LVEDV: r = 0.8333, p = 0.0154 | |
Ubiquitin domain-containing protein UBFD1 (UBFD1) | 182.3 | 1.00 × 10−4 | 0.045 | −0.487 | ||
Serine/threonine-protein kinase PAK 2 (PAK2) | 197.35 | 2.00 × 10−4 | 0.047 | −0.289 | ||
Beta-enolase (ENO3) | 12,210.88 | 2.00 × 10−4 | 0.047 | −0.419 | ||
Large ribosomal subunit protein uL15 (RPL27A) | 739.05 | 2.00 × 10−4 | 0.047 | 0.56 | ||
Myocardial zonula adherens protein (MYZAP) | 1227.59 | 2.00 × 10−4 | 0.047 | 0.514 | ||
Palladin (PALLD) | 1687.3 | 3.00 × 10−4 | 0.048 | −0.326 | ||
Supervillin (SVIL) | 903.31 | 3.00 × 10−4 | 0.049 | 0.411 | Septal thickness: r = 0.8452, p = 0.0062 |
Protein Name (Gene) | %CV | p adj DCM v oHCM | log2ratio DCM/oHCM | p adj ISCM v oHCM | log2ratio ISCM/oHCM | Clinical Correlations |
---|---|---|---|---|---|---|
Cytochrome c oxidase subunit 7A-related protein, mitochondrial (COX7A2L) | 5.6 | 0.001 | 0.091 | 0.004 | −0.476 | RVSP: r = −0.7381; p = 0.0458 |
Complement C1q subcomponent subunit A (C1QA) | 6.1 | 0.044 | −0.243 | 0.010 | 0.766 | LV Mass: r = 0.8333; p = 0.0154 |
Complement C2 (C2) | 3.1 | 0.023 | 0.444 | 0.007 | 0.838 | LV Mass: r = 0.7857, p = 0.0279 |
Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial (PDAH1) | 2.4 | 0.033 | 0.047 | 0.017 | −0.280 | LVEDV: r = 0.7667, p = 0.0214 |
Complement component C7 (C7) | 6.1 | 0.004 | −0.374 | 0.007 | 1.184 | LVEDD: r = 0.7888, p = 0.0036 |
Collagen alpha-2(VI) chain (COL6A2) | 2.6 | 0.046 | −0.118 | 0.001 | 1.045 | LVEF: r = 0.7224, p = 0.0098 |
Enoyl-CoA hydratase domain-containing protein 2, mitochondrial (ECHDC2) | 6.1 | 0.037 | −0.310 | 0.010 | −0.415 | BNP: r = 0–1.000, p = 0.0167 |
Zinc finger protein 397 (ZNF397) | 20.7 | 0.041 | 0.256 | 0.013 | −0.444 | LVEDV: r = 0.8833, p = 0.0031 |
Complement factor D (CFD) | 9.9 | 0.034 | 0.358 | 0.008 | 1.255 | LV Mass: r = 0.7619; p = 0.0368 Septal thickness: r = 0.7197, p = 0.0338 |
Complement C1q subcomponent subunit C (C1QC) | 6.0 | 0.026 | −0.260 | 0.008 | 0.928 | LVEDD: r = 0.6991, p = 0.0143 Post-amyl LVOT gradient: r = 0.8214, p = 0.0341 |
Complement component C9 (C9) | 5.0 | 0.009 | −0.129 | 0.008 | 0.998 | LVEDV: r = −0.7381, p = 0.0458 RVSP: r = 0.8571, p = 0.0107 |
C4b-binding protein alpha chain (C4BPA) | 4.5 | 0.031 | 0.000 | 0.005 | 0.991 | LVEDD: r = 0.5988, p = 0.0431 |
Attractin (ATRN) | 7.4 | 0.016 | −0.009 | 0.015 | 0.433 | LV Mass: r = 0.9048, p = 0.0046 |
Ceruloplasmin (CP) | 6.1 | 0.005 | 0.259 | 0.020 | 0.854 | |
Alpha-1-antitrypsin (SERPINA1) | 2.9 | 0.004 | −0.426 | 0.005 | 0.932 | |
Alpha-1-antichymotrypsin (SERPINA3) | 4.5 | 0.019 | −1.031 | 0.046 | 0.877 | |
Complement C3 (C3) | 2.8 | 0.038 | 0.287 | 0.036 | 0.615 | |
Plasma protease C1 inhibitor (SERPING1) | 5.1 | 0.007 | −0.295 | 0.008 | 0.791 | |
Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) | 1.4 | 0.012 | 0.295 | 0.021 | 0.641 | |
Homeodomain-interacting protein kinase 2 (HIPK2) | 21.7 | 0.001 | −0.009 | 0.000 | −0.648 |
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Tonry, C.; Linden, K.; Collier, P.; Ledwidge, M.; McDonald, K.; Collins, B.C.; Watson, C.J. Proteomic Characterisation of Heart Failure Reveals a Unique Molecular Phenotype for Hypertrophic Cardiomyopathy. Biomedicines 2024, 12, 1712. https://doi.org/10.3390/biomedicines12081712
Tonry C, Linden K, Collier P, Ledwidge M, McDonald K, Collins BC, Watson CJ. Proteomic Characterisation of Heart Failure Reveals a Unique Molecular Phenotype for Hypertrophic Cardiomyopathy. Biomedicines. 2024; 12(8):1712. https://doi.org/10.3390/biomedicines12081712
Chicago/Turabian StyleTonry, Claire, Katie Linden, Patrick Collier, Mark Ledwidge, Ken McDonald, Ben C. Collins, and Chris J. Watson. 2024. "Proteomic Characterisation of Heart Failure Reveals a Unique Molecular Phenotype for Hypertrophic Cardiomyopathy" Biomedicines 12, no. 8: 1712. https://doi.org/10.3390/biomedicines12081712
APA StyleTonry, C., Linden, K., Collier, P., Ledwidge, M., McDonald, K., Collins, B. C., & Watson, C. J. (2024). Proteomic Characterisation of Heart Failure Reveals a Unique Molecular Phenotype for Hypertrophic Cardiomyopathy. Biomedicines, 12(8), 1712. https://doi.org/10.3390/biomedicines12081712