Increased fibroblast accumulation in the equine heart following persistent atrial fibrillation

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Background: Fibroblasts maintain the extracellular matrix homeostasis and may couple to cardiomyocytes through gap junctions and thereby increase the susceptibility to slow conduction and cardiac arrhythmias, such as atrial fibrillation (AF). In this study, we used an equine model of persistent AF to characterize structural changes and the role of fibroblasts in the development of an arrhythmogenic substrate for AF. Material and methods: Eleven horses were subjected to atrial tachypacing until self-sustained AF developed and were kept in AF for six weeks. Horses in sinus rhythm (SR) served as control. In terminal open-chest experiments conduction velocity (CV) was measured. Tissue was harvested and stained from selected sites. Automated image analysis was performed to assess fibrosis, fibroblasts, capillaries and various cardiomyocyte characteristics. Results: Horses in SR showed a rate-dependent slowing of CV, while in horses with persistent AF this rate-dependency was completely abolished (CV•basic cycle length relation p = 0.0295). Overall and interstitial amounts of fibrosis were unchanged, but an increased fibroblast count was found in left atrial appendage, Bachmann's bundle, intraatrial septum and pulmonary veins (p < 0.05 for all) in horses with persistent AF. The percentage of α-SMA expressing fibroblasts remained the same between the groups. Conclusion: Persistent AF resulted in fibroblast accumulation in several regions, particularly in the left atrial appendage. The increased number of fibroblasts could be a mediator of altered electrophysiology during AF. Targeting the fibroblast proliferation and differentiation could potentially serve as a novel therapeutic target slowing down the structural remodeling associated with AF.

TidsskriftIJC Heart and Vasculature
StatusUdgivet - 2021

Bibliografisk note

Funding Information:
We acknowledge the assistance and facilities provided by the Core Facility for Integrated Microscopy (CFIM) at the Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.

Funding Information:
The study was funded by the European Union’s Horizon 2020 MSCA ITN under Grant Agreement No. 675351, The Independent Research Fund Denmark, DFF-7017–00050, The Kustos Foundation of 1881, Kirsten og Freddy Johansens Fond and Svenningsens Fond.

Publisher Copyright:
© 2021 The Authors

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