Journal article
CIB2 Is a Novel Endogenous Repressor of Atrial Remodeling
Circulation (New York, N.Y.), Vol.147(23), pp.1758-1776
06/06/2023
DOI: 10.1161/CIRCULATIONAHA.122.062660
PMID: 37128899
Abstract
BACKGROUND Atrial fibrillation (AF) is a highly prevalent condition that can cause or exacerbate heart failure, is an important risk factor for stroke, and is associated with pronounced morbidity and mortality. Genes uniquely expressed in the atria are known to be essential for maintaining atrial structure and function. Atrial tissue remodeling contributes to arrhythmia recurrence and maintenance. However, the mechanism underlying atrial remodeling remains poorly understood. This study was designed to investigate whether other uncharacterized atrial specific genes play important roles in atrial physiology and arrhythmogenesis. METHODS RNA-sequencing analysis was used to identify atrial myocyte specific and angiotensin II-responsive genes. Genetically modified, cardiomyocyte-specific mouse models (knockout and overexpression) were generated. In vivo and in vitro electrophysiological, histology, and biochemical analyses were performed to determine the consequences of CIB2 (calcium and integrin binding family member 2 protein) gain and loss of function in the atrium. RESULTS Using RNA-sequencing analysis, we identified CIB2 as an atrial-enriched protein that is significantly downregulated in the left atria of patients with AF and mouse models of AF from angiotensin II infusion or pressure overload. Using cardiomyocyte-specific Cib2 knockout (Cib2-/-) and atrial myocyte-specific Cib2-overexpressing mouse models, we found that loss of Cib2 enhances AF occurrence, prolongs AF duration, and correlates with a significant increase in atrial fibrosis under stress. Conversely, Cib2 overexpression mitigates AF occurrence and atrial fibrosis triggered by angiotensin II stress. Mechanistically, we revealed that CIB2 competes with and inhibits CIB1-mediated calcineurin activation, thereby negating stress-induced structural remodeling and AF. CONCLUSIONS Our data suggest that CIB2 represents a novel endogenous and atrial-enriched regulator that protects against atrial remodeling and AF under stress conditions. Therefore, CIB2 may represent a new potential target for treating AF.
Details
- Title: Subtitle
- CIB2 Is a Novel Endogenous Repressor of Atrial Remodeling
- Creators
- Yihui Wang - Shanghai First People's HospitalJizheng Wang - State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (Y.W., Jizheng Wang, X.C., C.C., K.Y., M.L., L.Z., F.L., L.S., S.Z.).Ling ShiXiuyu Chen - State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (Y.W., Jizheng Wang, X.C., C.C., K.Y., M.L., L.Z., F.L., L.S., S.Z.).Desheng Li - Ministry of Education of the People's Republic of ChinaChen Cui - State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (Y.W., Jizheng Wang, X.C., C.C., K.Y., M.L., L.Z., F.L., L.S., S.Z.).Kai Yang - State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (Y.W., Jizheng Wang, X.C., C.C., K.Y., M.L., L.Z., F.L., L.S., S.Z.).Minjie Lu - State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (Y.W., Jizheng Wang, X.C., C.C., K.Y., M.L., L.Z., F.L., L.S., S.Z.).Jinhua Huang - Union HospitalLei Zhang - State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (Y.W., Jizheng Wang, X.C., C.C., K.Y., M.L., L.Z., F.L., L.S., S.Z.).Fei Li - State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (Y.W., Jizheng Wang, X.C., C.C., K.Y., M.L., L.Z., F.L., L.S., S.Z.).Jinxi Wang - University of IowaBiyi Chen - University of IowaBin Wang - First Affiliated Hospital of Shantou University Medical CollegeDuane D Hall - University of IowaZhenwei Pan - Harbin Medical UniversityJiang Hong - Shanghai First People's HospitalLong-Sheng Song - University of IowaLei Song - Ministry of Education of the People's Republic of ChinaShihua Zhao - State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (Y.W., Jizheng Wang, X.C., C.C., K.Y., M.L., L.Z., F.L., L.S., S.Z.).
- Resource Type
- Journal article
- Publication Details
- Circulation (New York, N.Y.), Vol.147(23), pp.1758-1776
- DOI
- 10.1161/CIRCULATIONAHA.122.062660
- PMID
- 37128899
- NLM abbreviation
- Circulation
- eISSN
- 1524-4539
- Language
- English
- Electronic publication date
- 05/02/2023
- Date published
- 06/06/2023
- Academic Unit
- Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9984400758002771
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