Related Experiment Video
Updated: Sep 17, 2025

Optimization of Transesophageal Atrial Pacing to Assess Atrial Fibrillation Susceptibility in Mice
Published on: June 29, 2022
Atrial Fibroblasts-Derived Extracellular Vesicles Exacerbate Atrial Arrhythmogenesis
Yue Yuan1, Xinbo Zhao1, Xuejie Han1
1Department of Cardiology, The First Affiliated Hospital, Harbin Medical University, Harbin, 150001, China.
None:
Cardiac fibroblasts (CFs) secrete exosomes, and their cargo represents a new means of cellular communication in cardiovascular diseases, including atrial fibrillation (AF). We aimed to explore the contribution of atial CFs (ACFs)-derived exosomes to AF development. Cultured primary human ACFs (hACFs) and rat ACFs are treated with angiotensin II, and the secreted exosomes are transferred to rats. Action potential duration and L-type calcium current (ICa) are tested. Global microRNA-224-5p knock-in and fibroblast-specific microRNA-224-5p knock-in (FMKI) mice underwent an inducible AF test. Transferred exosomes of Ang II-induced hACFs and primary adult rat ACFs increased AF incidence and prolonged AF duration. The inhibitor of exosomes and knockdown of Dicer rescued the AF phenotype. MicroRNA array suggested upregulated microRNA-224-5p level in both primary adult rat ACFs and ACFs-secreted exosomes. microRNA-224-5p agonist shortened atrial effective refractory period (AERP) and promoted AF. Mechanistically, microRNA-224-5p bound to CACNA1C and inhibited its transcription. Moreover, global microRNA-224-5p knock-in and FMKI mice exhibited increased inducible AF incidence, accompanied by diminished ICa current in ACMs. Exosome microRNA-224-5p is enhanced in ACFs isolated from atria and plasma of AF patients, and positively correlated with recurrence after radiofrequency ablation. In summary, ACFs-derived exosome microRNA-224-5p contributes to AF by inhibiting CACNA1C to drive atrial electrical remodeling.
Related Concept Videos
ECG Interpretation of Arrhythmias II: Atrial, Junctional and Ventricular Arrhythmias
Mechanism of Cardiac Arrhythmias
Disturbances in Heart Rhythm
Arrhythmias are categorized by their speed, rhythm, and origin. A slow heart...
Heart Failure II: Pathophysiology
Rheumatic Heart Disease I: Introduction
Introduction to Fibroblasts

