ArticleJournal of the American College of Cardiology2014
Coxsackie and adenovirus receptor is a modifier of cardiac conduction and arrhythmia vulnerability in the setting of myocardial ischemia.
Article in Journal of the American College of Cardiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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32 citing papers in PubMed, 64 citations in OpenAlex.
- Single-cell RNA sequencing identifies CXADR as a fate determinant of the placental exchange surface.Nature communications · 2025Article
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- Genetics of Sudden Cardiac Arrest: Overview of Genetic Risk Factors and Aetiologies.Arrhythmia & electrophysiology review · 2025Review
- Microtubule plus-end tracking proteins: novel modulators of cardiac sodium channels and arrhythmogenesis.Cardiovascular research · 2023Article
- The intercalated disc: a unique organelle for electromechanical synchrony in cardiomyocytes.Physiological reviews · 2023Review
- CAR links hypoxia signaling to improved survival after myocardial infarction.Experimental & molecular medicine · 2023Article
- CXADR: From an Essential Structural Component to a Vital Signaling Mediator in Spermatogenesis.International journal of molecular sciences · 2023Review
- Circulating virome and inflammatory proteome in patients with ST-elevation myocardial infarction and primary ventricular fibrillation.Scientific reports · 2022Article
- Human Coxsackie- and adenovirus receptor is a putative target of neutrophil elastase-mediated shedding.Molecular biology reports · 2022Article
- Understanding the molecular basis of cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2022Review
- Genomic and Non-Genomic Regulatory Mechanisms of the Cardiac Sodium Channel in Cardiac Arrhythmias.International journal of molecular sciences · 2022Review
- Targeting the Microtubule EB1-CLASP2 Complex Modulates NaCirculation research · 2021Article
- Structural and Functional Characterization of a NaCirculation research · 2021Article
- Small G-protein RhoA is a potential inhibitor of cardiac fast sodium current.Journal of physiology and biochemistry · 2021Article
- FAT10 protects against ischemia-induced ventricular arrhythmia by decreasing Nedd4-2/Nav1.5 complex formation.Cell death & disease · 2021Article
- Coxsackievirus and Adenovirus Receptor (CXADR): Recent Findings and Its Role and Regulation in Spermatogenesis.Advances in experimental medicine and biology · 2021Review
- The sodium channel NaActa physiologica (Oxford, England) · 2020Article
- Heritable arrhythmia syndromes associated with abnormal cardiac sodium channel function: ionic and non-ionic mechanisms.Cardiovascular research · 2020Review
- Seasonality of ventricular fibrillation at first myocardial infarction and association with viral exposure.PloS one · 2020Article
- From Genome-Wide Association Studies to Cardiac Electrophysiology: Through the Maze of Biological Complexity.Frontiers in physiology · 2020Review
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21 authors at 8 institutions in 5 countries.
Funding
Abstract
objectivesThe aim of this study was to investigate the modulatory effect of the coxsackie and adenovirus receptor (CAR) on ventricular conduction and arrhythmia vulnerability in the setting of myocardial ischemia.
backgroundA heritable component in the risk of ventricular fibrillation during myocardial infarction has been well established. A recent genome-wide association study of ventricular fibrillation during acute myocardial infarction led to the identification of a locus on chromosome 21q21 (rs2824292) in the vicinity of the CXADR gene. CXADR encodes the CAR, a cell adhesion molecule predominantly located at the intercalated disks of the cardiomyocyte.
methodsThe correlation between CAR transcript levels and rs2824292 genotype was investigated in human left ventricular samples. Electrophysiological studies and molecular analyses were performed using CAR haploinsufficient (CAR⁺/⁻) mice.
resultsIn human left ventricular samples, the risk allele at the chr21q21 genome-wide association study locus was associated with lower CXADR messenger ribonucleic acid levels, suggesting that decreased cardiac levels of CAR predispose to ischemia-induced ventricular fibrillation. Hearts from CAR⁺/⁻ mice displayed slowing of ventricular conduction in addition to an earlier onset of ventricular arrhythmias during the early phase of acute myocardial ischemia after ligation of the left anterior descending artery. Expression and distribution of connexin 43 were unaffected, but CAR⁺/⁻ hearts displayed increased arrhythmia susceptibility on pharmacological electrical uncoupling. Patch-clamp analysis of isolated CAR⁺/⁻ myocytes showed reduced sodium current magnitude specifically at the intercalated disk. Moreover, CAR coprecipitated with NaV1.5 in vitro, suggesting that CAR affects sodium channel function through a physical interaction with NaV1.5.
conclusionsCAR is a novel modifier of ventricular conduction and arrhythmia vulnerability in the setting of myocardial ischemia. Genetic determinants of arrhythmia susceptibility (such as CAR) may constitute future targets for risk stratification of potentially lethal ventricular arrhythmias in patients with coronary artery disease.
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