Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of mouse heart samples from individuals with homozygous or heterozygous mutant alleles of Lamin A (LMNA)

ABSTRACT: This SuperSeries is composed of the following subset Series:; GSE6397: Comparison between gene expression in heart from Lmna H222P heterozygous and control mice; GSE6398: Comparison between gene expression in heart from Lmna H222P homozygous and control mice Experiment Overall Design: Refer to individual Series

ORGANISM(S): Mus musculus

SUBMITTER: Antoine Muchir

PROVIDER: E-GEOD-8000 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Activation of MAPK pathways links LMNA mutations to cardiomyopathy in Emery-Dreifuss muscular dystrophy.

Muchir Antoine A Pavlidis Paul P Decostre Valérie V Herron Alan J AJ Arimura Takuro T Bonne Gisèle G Worman Howard J HJ

The Journal of clinical investigation 20070419 5

Mutations in LMNA, which encodes nuclear Lamins A and C cause diseases affecting various organs, including the heart. We have determined the effects of an Lmna H222P mutation on signaling pathways involved in the development of cardiomyopathy in a knockin mouse model of autosomal dominant Emery-Dreifuss muscular dystrophy. Analysis of genome-wide expression profiles in hearts using Affymetrix GeneChips showed statistically significant differences in expression of genes in the MAPK pathways at th ...[more]

PMID: 17446932

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Project description: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.

Dataset Information

Transcription profiling of mouse heart samples from individuals with homozygous or heterozygous mutant alleles of Lamin A (LMNA)

Publications

Activation of MAPK pathways links LMNA mutations to cardiomyopathy in Emery-Dreifuss muscular dystrophy.

Similar Datasets

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