TY - JOUR

T1 - Increased fibroblast accumulation in the equine heart following persistent atrial fibrillation

AU - Saljic, Arnela

AU - Friederike Fenner, Merle

AU - Winters, Joris

AU - Flethøj, Mette

AU - Eggert Eggertsen, Caroline

AU - Carstensen, Helena

AU - Dalgas Nissen, Sarah

AU - Melis Hesselkilde, Eva

AU - van Hunnik, Arne

AU - Schotten, Ulrich

AU - Sørensen, Ulrik

AU - Jespersen, Thomas

AU - Verheule, Sander

AU - Buhl, Rikke

N1 - Publisher Copyright: © 2021 The Authors

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - Atrial fibrillation

KW - Equine

KW - Fibroblast

KW - Structural remodeling

U2 - 10.1016/j.ijcha.2021.100842

DO - 10.1016/j.ijcha.2021.100842

M3 - Journal article

C2 - 34355058

AN - SCOPUS:85110752063

VL - 35

JO - IJC Heart and Vasculature

JF - IJC Heart and Vasculature

SN - 2352-9067

M1 - 100842

ER -