Dataset Information

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

ABSTRACT: Background: Lamins A/C (encoded by the LMNA gene) can lead to dilated cardiomyopathy (DCM). Objectives: This study sought to undertake proteomic analysis of myocardial tissue to explore the postgenomic phenotype of end-stage lamin heart disease. Methods: Consecutive patients with end-stage lamin heart disease (LMNA-group, n=7) and ischaemic DCM (ICM-group, n=7) undergoing heart transplantation were enrolled. Samples were obtained from left atrium(LA), left ventricle(LV), right atrium(RA), right ventricle(RV) and interventricular septum(IVS). Liquid chromatography combined with mass-spectrometry was used for protein quantification. We compared protein concentrations in cardiac samples between LMNA and ICM groups. Proteins were considered differentially abundant if the quantitative difference was 1.5-fold and corrected p-value <0.05 at a false discovery rate of 0.01. Gene ontology(GO) enrichment analysis explored the related biological processes. Results: 4,247 proteins were identified in LMNA and ICM samples, of which 633 were differentially abundant in LA, 39 in LV, 181 in RA, 52 in RV, and 85 in IVS. Abundance of lamin A/C was reduced but lamin B (LMNB) increased in LMNA LA/RA tissue compared to ICM, but not in LV/RV. Transthyretin was more abundant in the LV/RV of LMNA compared to ICM while sarcomeric proteins such as titin and cardiac myosin heavy chain were generally reduced in RA/LA of LMNA. Protein expression profiling and GO enrichment analysis revealed sarcopenia, extracellular matrix(ECM) remodeling, deficient myocardial energetics, redox imbalances, and abnormal calcium handling in LMNA samples. Conclusion: Lamin heart disease is a biventricular and biatrial disease, characterized by sarcopenia, aberrant metabolism, and ECM remodeling. LMNB and transthyretin were unexpectedly abundant in the atria and ventricles respectively of patients with end-stage lamin heart disease potentially hinting to the possibility of compensatory responses.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Heart

DISEASE(S): Myocardial Ischemia

SUBMITTER: Gabriella Captur

LAB HEAD: Gabriella Captur

PROVIDER: PXD040488 | Pride | 2024-01-26

REPOSITORIES: Pride

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			Action	DRS
	2649-UCL-R01.kit	Other
	2649-UCL-R11_Report.xls	Xls
	G_D210329_MDDA_P2649_SExp01-F1_R01.raw	Raw
	G_D210329_MDDA_P2649_SExp01-F2_R01.raw	Raw
	G_D210329_MDDA_P2649_SExp01-F3_R01.raw	Raw

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

Topriceanu Constantin-Cristian CC Alfarih Mashael M Hughes Alun D AD Shiwani Hunain H Chan Fiona F Mohiddin Saidi A SA Moody William W Steeds Richard P RP O'Brien Benjamin B Vowinckel Jakob J Syrris Petros P Coats Caroline C Pettit Stephen S Arbustini Eloisa E Moon James C JC Captur Gabriella G

Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology 20230930 2-3

Lamins A/C (encoded by <i>LMNA</i> 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), avoidi ...[more]

PMID: 38090549

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