دورية أكاديمية
Cardiac-specific overexpression of CREM-IbΔC-X via CRISPR/Cas9 in mice presents a new model of atrial cardiomyopathy with spontaneous atrial fibrillation.
| العنوان: | Cardiac-specific overexpression of CREM-IbΔC-X via CRISPR/Cas9 in mice presents a new model of atrial cardiomyopathy with spontaneous atrial fibrillation. |
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| المؤلفون: | Chen J; Division of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 300# Guangzhou Road, Nanjing 210029, China., Qin H; Division of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 300# Guangzhou Road, Nanjing 210029, China., Hao J; Division of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 300# Guangzhou Road, Nanjing 210029, China., Wang Q; Division of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 300# Guangzhou Road, Nanjing 210029, China., Chen S; Division of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 300# Guangzhou Road, Nanjing 210029, China., Yang G; Division of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 300# Guangzhou Road, Nanjing 210029, China., Li M; Division of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 300# Guangzhou Road, Nanjing 210029, China., Zhu X; Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China., Wang D; Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China., Chen H; Division of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 300# Guangzhou Road, Nanjing 210029, China. Electronic address: chenhongwu@njmu.edu.cn., Cui C; Division of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 300# Guangzhou Road, Nanjing 210029, China. Electronic address: cuichang@njmu.edu.cn., Chen M; Division of Cardiology, The First Affiliated Hospital of Nanjing Medical University, 300# Guangzhou Road, Nanjing 210029, China. |
| المصدر: | Translational research : the journal of laboratory and clinical medicine [Transl Res] 2024 May; Vol. 267, pp. 54-66. Date of Electronic Publication: 2024 Jan 08. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 101280339 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1810 (Electronic) Linking ISSN: 18781810 NLM ISO Abbreviation: Transl Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: New York, N.Y. : Elsevier, [2006]- |
| مواضيع طبية MeSH: | Atrial Fibrillation* , Cardiomyopathies*/genetics, Mice ; Humans ; Animals ; CRISPR-Cas Systems/genetics ; Mice, Transgenic ; Heart Atria/pathology ; Cyclic AMP Response Element Modulator/genetics ; Cyclic AMP Response Element Modulator/metabolism |
| مستخلص: | Atrial cardiomyopathy (ACM) forms the substrate for atrial fibrillation (AF) and underlies the potential for atrial thrombus formation and subsequent stroke. However, generating stable animal models that accurately replicate the entire progression of atrial lesions, particularly the onset of AF, presents significant challenges. In the present study, we found that the isoform of CRE-binding protein modulator (CREM-IbΔC-X), which is involved in the regulation of cardiac development and atrial rhythm, was highly expressed in atrial biopsies from patients with AF. Building upon this finding, we employed CRISPR/Cas9 technology to create a mouse model with cardiac-specific overexpression of CREM-IbΔC-X (referred to as CS-CREM mice). This animal model effectively illustrated the development of ACM through electrophysiological and structural remodelings over time. Proteomics and Chip-qPCR analysis of atrial samples revealed significant upregulation of cell-matrix adhesion and extracellular matrix structural components, alongside significant downregulation of genes related to atrial functions in the CS-CREM mice. Furthermore, the corresponding responses to anti-arrhythmia drugs, i.e., amiodarone and propafenone, suggested that CS-CREM mice could serve as an ideal in vivo model for drug testing. Our study introduced a novel ACM model with spontaneous AF by cardiac-specifically overexpressing CREM-IbΔC-X in mice, providing valuable insights into the mechanisms and therapeutic targets of ACM. Competing Interests: Declaration of competing interest The authors declare that there are no competing interests. (Copyright © 2024 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Atrial cardiomyopathy; Atrial fibrillation; Atrial fibrosis; CRISPR/Cas9; Proteomics |
| المشرفين على المادة: | 0 (CREM protein, human) 135844-64-3 (Cyclic AMP Response Element Modulator) |
| تواريخ الأحداث: | Date Created: 20240110 Date Completed: 20240410 Latest Revision: 20240410 |
| رمز التحديث: | 20240410 |
| DOI: | 10.1016/j.trsl.2024.01.001 |
| PMID: | 38199433 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1878-1810 |
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| DOI: | 10.1016/j.trsl.2024.01.001 |