دورية أكاديمية
Atrial proteomic profiling reveals a switch towards profibrotic gene expression program in CREM-IbΔC-X mice with persistent atrial fibrillation.
العنوان: | Atrial proteomic profiling reveals a switch towards profibrotic gene expression program in CREM-IbΔC-X mice with persistent atrial fibrillation. |
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المؤلفون: | Zhao S; Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX 77030, USA; Department of Integrative Physiology, Baylor College of Medicine, Houston, TX 77030, USA., Hulsurkar MM; Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX 77030, USA; Department of Integrative Physiology, Baylor College of Medicine, Houston, TX 77030, USA., Lahiri SK; Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX 77030, USA; Department of Integrative Physiology, Baylor College of Medicine, Houston, TX 77030, USA., Aguilar-Sanchez Y; Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX 77030, USA; Department of Integrative Physiology, Baylor College of Medicine, Houston, TX 77030, USA., Munivez E; Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX 77030, USA; Department of Integrative Physiology, Baylor College of Medicine, Houston, TX 77030, USA., Müller FU; Institute of Pharmacology and Toxicology, University of Münster, Münster, Germany., Jain A; Mass Spectrometry Proteomics Core, Baylor College of Medicine, Houston, TX, USA., Malovannaya A; Mass Spectrometry Proteomics Core, Baylor College of Medicine, Houston, TX, USA; Department of Biochemistry, Baylor College of Medicine, Houston, TX 77030, USA., Yiu CHK; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, British Heart Foundation Centre of Research Excellence, NIHR Oxford BRC, University of Oxford, John Radcliffe Hospital, Oxford, UK., Reilly S; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, British Heart Foundation Centre of Research Excellence, NIHR Oxford BRC, University of Oxford, John Radcliffe Hospital, Oxford, UK., Wehrens XHT; Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX 77030, USA; Department of Integrative Physiology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Medicine (in Cardiology), Baylor College of Medicine, Houston, TX 77030, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pediatrics (in Cardiology), Baylor College of Medicine, Houston, TX 77030, USA; Center for Space Medicine, Baylor College of Medicine, Houston, USA. Electronic address: wehrens@bcm.edu. |
المصدر: | Journal of molecular and cellular cardiology [J Mol Cell Cardiol] 2024 May; Vol. 190, pp. 1-12. Date of Electronic Publication: 2024 Mar 19. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Academic Press Country of Publication: England NLM ID: 0262322 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-8584 (Electronic) Linking ISSN: 00222828 NLM ISO Abbreviation: J Mol Cell Cardiol Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: London, New York, Academic Press. |
مواضيع طبية MeSH: | Atrial Fibrillation*/metabolism , Atrial Fibrillation*/genetics , Cyclic AMP Response Element Modulator*/metabolism , Cyclic AMP Response Element Modulator*/genetics , Proteomics*/methods , Heart Atria*/metabolism , Heart Atria*/pathology , Mice, Transgenic* , Fibrosis*, Animals ; Mice ; Gene Expression Regulation ; Protein Interaction Maps ; Proteome/metabolism ; Disease Models, Animal ; Gene Expression Profiling ; Extracellular Matrix/metabolism ; Male |
مستخلص: | 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 structural 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 reminiscent of those seen in 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. Competing Interests: Declaration of competing interest XHTW is a founding partner and shareholder of Elex Biotech Inc., a start-up company that developed drug molecules that target ryanodine receptors to treat cardiac arrhythmia disorders. Other authors have no conflict of interest to declare. (Copyright © 2024 Elsevier Ltd. All rights reserved.) |
التعليقات: | Update of: bioRxiv. 2024 Jan 12:2024.01.10.575097. doi: 10.1101/2024.01.10.575097. (PMID: 38260363) |
معلومات مُعتمدة: | FS/SBSRF/22/31033 United Kingdom BHF_ British Heart Foundation |
فهرسة مساهمة: | Keywords: Atrial fibrillation; Atrial fibrosis; Disease model; Extracellular matrix; Proteomics |
المشرفين على المادة: | 135844-64-3 (Cyclic AMP Response Element Modulator) 0 (Proteome) 0 (Crem protein, mouse) |
تواريخ الأحداث: | Date Created: 20240321 Date Completed: 20240430 Latest Revision: 20240724 |
رمز التحديث: | 20240725 |
DOI: | 10.1016/j.yjmcc.2024.03.003 |
PMID: | 38514002 |
قاعدة البيانات: | MEDLINE |
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