The atrial and ventricular myocardial proteome of end-stage lamin heart disease

• Published in: Acta myologica 2023, Vol.42 (2-3), p.43-52
• Main Authors: Topriceanu, Constantin-Cristian, Alfarih, Mashael, Hughes, Alun D, Shiwani, Hunain, Chan, Fiona, Mohiddin, Saidi A., Moody, William, Steeds, Richard P., O’Brien, Benjamin, Vowinckel, Jakob, Syrris, Petros, Coats, Caroline, Pettit, Stephen, Arbustini, Eloisa, Moon, James C., Captur, Gabriella
• Format: Article
• Language: English
• Subjects: Original
• ISSN: 1128-2460; 2532-1900
• DOI: 10.36185/2532-1900-339

Lamins A/C (encoded by LMNA gene) can lead to dilated cardiomyopathy (DCM). This pilot study sought to explore the postgenomic phenotype of end-stage lamin heart disease. Consecutive patients with end-stage lamin heart disease (LMNA-group, n = 7) and ischaemic DCM (ICM-group, n = 7) undergoing heart transplantation were prospectively enrolled. Samples were obtained from left atrium (LA), left ventricle (LV), right atrium (RA), right ventricle (RV) and interventricular septum (IVS), avoiding the infarcted myocardial segments in the ICM-group. Samples were analysed using a discovery ‘shotgun’ proteomics approach. We found that 990 proteins were differentially abundant between LMNA and ICM samples with the LA being most perturbed (16-fold more than the LV). Abundance of lamin A/C protein was reduced, but lamin B increased in LMNA LA/RA tissue compared to ICM, but not in LV/RV. Carbonic anhydrase 3 (CA3) was over-abundant across all LMNA tissue samples (LA, LV, RA, RV, and IVS) when compared to ICM. Transthyretin was more abundant in the LV/RV of LMNA compared to ICM, while sarcomeric proteins such as titin and cardiac alpha-cardiac myosin heavy chain were generally less abundant in RA/LA of LMNA. Protein expression profiling and enrichment analysis pointed towards sarcopenia, extracellular matrix remodeling, deficient myocardial energetics, redox imbalances, and abnormal calcium handling in LMNA samples. Compared to ICM, end-stage lamin heart disease is a biventricular but especially a biatrial disease appearing to have an abundance of lamin B, CA3 and transthyretin, potentially hinting to compensatory responses.