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International journal of cardiology. Heart & vasculature2021; 35; 100842; doi: 10.1016/j.ijcha.2021.100842

Increased fibroblast accumulation in the equine heart following persistent atrial fibrillation.

Abstract: 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. 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. Conclusions: 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.
© 2021 The Authors.
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Publication Date: 2021-07-20 PubMed ID: 34355058PubMed Central: PMC8322305DOI: 10.1016/j.ijcha.2021.100842Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article investigates the structural changes and the role of fibroblasts, a type of cell that synthesizes the extracellular matrix, in equine hearts following persistent atrial fibrillation (AF), a common type of abnormal heart rhythm. Notably, the research emphasizes on the potential of fibroblast proliferation and differentiation as a novel therapeutic target for mitigating structural remodeling associated with AF.

Methods

  • The researchers used an equine model and subjected eleven horses to atrial tachypacing until they developed self-sustained atrial fibrillation (AF); these horses were kept in this AF state for six weeks.
  • Horses in sinus rhythm (SR) served as control subjects.
  • In terminal open-chest experiments, conduction velocity, which measures the speed at which the heart’s electrical signals travel, was evaluated.
  • Tissue samples were collected and stained from selected areas. An automated image analysis was then conducted to assess fibrosis (tissue scarring), fibroblasts (cells responsible for producing the extracellular matrix), capillaries, and various cardiomyocyte (heart muscle cell) characteristics.

Results

  • Control horses in sinus rhythm demonstrated a rate-dependent slowing of the conduction velocity. However, this rate-dependency was entirely abolished in horses with persistent atrial fibrillation.
  • While overall and interstitial amounts of fibrosis remained unchanged, an increased count of fibroblasts was noted in specific areas of the heart such as the left atrial appendage, Bachmann’s bundle, intraatrial septum, and pulmonary veins in horses with persistent AF.
  • The percentage of α-SMA expressing fibroblasts was the same between both groups.

Conclusions

  • Persistent atrial fibrillation led to an accumulation of fibroblasts in several regions of the heart, primarily in the left atrial appendage.
  • The study suggests that the increased number of fibroblasts could influence the altered electrophysiology observed during AF.
  • Therefore, the researchers proposed that targeting fibroblast proliferation and differentiation, through new therapeutic strategies, could potentially slow down the structural changes associated with AF.

Cite This Article

APA
Saljic A, Friederike Fenner M, Winters J, Flethøj M, Eggert Eggertsen C, Carstensen H, Dalgas Nissen S, Melis Hesselkilde E, van Hunnik A, Schotten U, Sørensen U, Jespersen T, Verheule S, Buhl R. (2021). Increased fibroblast accumulation in the equine heart following persistent atrial fibrillation. Int J Cardiol Heart Vasc, 35, 100842. https://doi.org/10.1016/j.ijcha.2021.100842

Publication

International journal of cardiology. Heart & vasculature
ISSN: 2352-9067
NlmUniqueID: 101649525
Country: Ireland
Language: English
Volume: 35
Pages: 100842

Researcher Affiliations

Saljic, Arnela
  • Laboratory of Cardiac Physiology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark.
Friederike Fenner, Merle
  • Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Agrovej 8, DK-2630 Taastrup, Denmark.
  • Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Grønnegårdsvej 7, 1870 Frederiksberg, Denmark.
Winters, Joris
  • Department of Physiology, Maastricht University, Maastricht, Netherlands.
Flethøj, Mette
  • Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Agrovej 8, DK-2630 Taastrup, Denmark.
Eggert Eggertsen, Caroline
  • Laboratory of Cardiac Physiology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark.
Carstensen, Helena
  • Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Agrovej 8, DK-2630 Taastrup, Denmark.
Dalgas Nissen, Sarah
  • Laboratory of Cardiac Physiology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark.
Melis Hesselkilde, Eva
  • Laboratory of Cardiac Physiology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark.
van Hunnik, Arne
  • Department of Physiology, Maastricht University, Maastricht, Netherlands.
Schotten, Ulrich
  • Department of Physiology, Maastricht University, Maastricht, Netherlands.
Sørensen, Ulrik
  • Acesion Pharma ApS, Copenhagen, Denmark.
Jespersen, Thomas
  • Laboratory of Cardiac Physiology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark.
Verheule, Sander
  • Department of Physiology, Maastricht University, Maastricht, Netherlands.
Buhl, Rikke
  • Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Agrovej 8, DK-2630 Taastrup, Denmark.

Conflict of Interest Statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Citations

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