Related Experiment Video
Updated: Jul 5, 2025
08:05
Optimization of Transesophageal Atrial Pacing to Assess Atrial Fibrillation Susceptibility in Mice
Published on: June 29, 2022
2.8K
Interleukin-33/ST2 axis involvement in atrial remodeling and arrhythmogenesis
Tzu-Yu Cheng1, Yao-Chang Chen2, Shao-Jung Li3
1Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan; Division of Cardiovascular Surgery, Department of Surgery, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan.
Summary
Interleukin-33 (IL-33) signaling promotes atrial remodeling and arrhythmia by activating suppression of tumorigenicity 2 (ST2). Blocking this IL-33/ST2 axis may offer a novel therapeutic strategy for atrial fibrillation.
Area of Science:
- Cardiology
- Immunology
- Molecular Biology
Background:
- Interleukin-33 (IL-33) is a cytokine implicated in immune responses.
- Elevated IL-33 levels are observed in atrial fibrillation (AF).
- The specific role of IL-33/ST2 signaling in atrial arrhythmia remains unclear.
Purpose of the Study:
- To investigate the pathological effects of the IL-33/ST2 axis on atrial remodeling and arrhythmogenesis.
- To explore the potential therapeutic implications of targeting the IL-33/ST2 pathway.
Main Methods:
- Utilized HL-1 atrial myocytes treated with IL-33 and/or anti-ST2 antibodies.
- Performed patch clamping, confocal microscopy, and Western blotting to assess cellular electrophysiology and protein activity.
- Conducted in vivo studies in mice using telemetric ECG, Masson's trichrome staining, and immunohistochemistry.
Main Results:
- IL-33 treatment in myocytes reduced action potential duration, L-type Ca2+ current, and increased sarcoplasmic reticulum Ca2+ content, NCX current, and intracellular calcium transients.
- IL-33 activated CaMKII/RyR2 and NF-κB/NLRP3 signaling pathways, increasing expression of Nav1.5, Kv1.5, NCX, and NLRP3.
- In mice, IL-33 induced atrial ectopic beats, AF episodes, atrial fibrosis, and elevated NF-κB/NLRP3 signaling, effects attenuated by anti-ST2 antibody pretreatment.
Conclusions:
- IL-33 promotes atrial remodeling and arrhythmogenesis via ST2 signaling.
- The IL-33/ST2 axis plays a significant role in the pathophysiology of atrial arrhythmia.
- Inhibition of the IL-33/ST2 axis presents a potential therapeutic strategy for atrial arrhythmia, particularly in patients with elevated IL-33.
Related Concept Videos
01:17Intracellular Signaling Affects Focal Adhesions
2.7K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.7K
01:28Mechanism of Cardiac Arrhythmias
922
Arrhythmias are irregular heart rhythms occurring when the heart's electrical impulses become abnormal. These disturbances can lead to various symptoms, depending on their severity and the underlying cause. Some common factors contributing to arrhythmias include hypoxia, ischemia, electrolyte imbalances, excessive catecholamine exposure, drug toxicity, and muscle overstretching. Arrhythmias can be classified into two main types based on the rate and site of origin of abnormal heart rhythms.
922
01:24T Cell Types and Functions
1.0K
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
1.0K
01:24Antiarrhythmic Drugs: Class II Agents as β-Adrenergic Blockers
746
Adrenergic stimulation generally impacts cardiac rate and rhythm. Specifically, stimulation of the β-adrenoceptors triggers an increase in intracellular calcium ion influx and pacemaker currents, which may cause arrhythmias. Catecholamines like adrenaline also demonstrate β2-adrenoceptor-mediated hypokalemia, impacting cardiac action potential and disrupting the normal cardiac rhythm. Class II antiarrhythmic drugs are β-adrenoceptor antagonists or β-blockers, which...
746
01:12Antiarrhythmic Drugs: Class III Agents as Potassium Channel Blockers
1.0K
Class III antiarrhythmic drugs are a group of medications that can prolong action potentials in the heart. They achieve this by blocking potassium channels or enhancing inward currents from sodium channels. However, these drugs have a unique property of "reverse use-dependence," which is most pronounced at slower heart rates and can lead to torsades de pointes—a specific type of arrhythmia. However, it is essential to note that excessive QT interval prolongation—a measure of...
1.0K