Language
English
Publication Date
1-12-2024
Journal
bioRxiv
DOI
10.1101/2024.01.10.575097
PMID
38260363
PMCID
PMC10802622
PubMedCentral® Posted Date
1-12-2024
PubMedCentral® Full Text Version
Pre-Print
Abstract
Background: Overexpression of the CREM (cAMP response element-binding modulator) isoform CREM-IbΔC-X in transgenic mice (CREM-Tg) causes the age-dependent development of spontaneous AF.
Purpose: To identify key proteome signatures and biological processes accompanying the development of persistent AF through integrated proteomics and bioinformatics analysis.
Methods: Atrial tissue samples from three CREM-Tg mice and three wild-type littermates were subjected to unbiased mass spectrometry-based quantitative proteomics, differential expression and pathway enrichment analysis, and protein-protein interaction (PPI) network analysis.
Results: A total of 98 differentially expressed proteins were identified. Gene ontology analysis revealed enrichment for biological processes regulating actin cytoskeleton organization and extracellular matrix (ECM) dynamics. Changes in ITGAV, FBLN5, and LCP1 were identified as being relevant to atrial fibrosis and remodeling based on expression changes, co-expression patterns, and PPI network analysis. Comparative analysis with previously published datasets revealed a shift in protein expression patterns from ion-channel and metabolic regulators in young CREM-Tg mice to profibrotic remodeling factors in older CREM-Tg mice. Furthermore, older CREM-Tg mice exhibited protein expression patterns that resembled those of humans with persistent AF.
Conclusions: This study uncovered distinct temporal changes in atrial protein expression patterns with age in CREM-Tg mice consistent with the progressive evolution of AF. Future studies into the role of the key differentially abundant proteins identified in this study in AF progression may open new therapeutic avenues to control atrial fibrosis and substrate development in AF.
Keywords
Atrial fibrillation, atrial fibrosis, extracellular matrix, disease model, proteomics, atrial remodeling, fibrosis
Published Open-Access
yes
Recommended Citation
Zhao, Shuai; Hulsurkar, Mohit M; Lahiri, Satadru K; et al., "Atrial Proteomic Profiling Reveals a Switch Towards Profibrotic Gene Expression Program in CREM-IbΔC-X Mice with Persistent Atrial Fibrillation" (2024). Faculty, Staff and Students Publications. 8149.
https://digitalcommons.library.tmc.edu/baylor_docs/8149
Comments
Updated version available: A peer-reviewed version of this article, "Atrial proteomic profiling reveals a switch towards profibrotic gene expression program in CREM-IbΔC-X mice with persistent atrial fibrillation.", has been published in J Mol Cell Cardiol.