Atrial fibrillation in human patients is associated with increased collagen type V and TGFbeta1

Sawa Kostin; Manfred Richter; Natalia Ganceva; Benjamin Sasko; Theodoros Giannakopoulos; Oliver Ritter; Zoltan Szalay; Nikolaos Pagonas

doi:10.1016/j.ijcha.2023.101327

Atrial fibrillation in human patients is associated with increased collagen type V and TGFbeta1

Int J Cardiol Heart Vasc. 2023 Dec 27:50:101327. doi: 10.1016/j.ijcha.2023.101327. eCollection 2024 Feb.

Authors

Sawa Kostin¹, Manfred Richter², Natalia Ganceva³, Benjamin Sasko⁴, Theodoros Giannakopoulos⁵, Oliver Ritter^{1

5}, Zoltan Szalay², Nikolaos Pagonas^{1

6}

Affiliations

¹ Faculty of Health Sciences Brandenburg, Brandenburg Medical School Theodor Fontane, Neuruppin, Germany.
² Department of Cardiac Surgery, Kerckhoff-Clinic, Bad Nauheim, Germany.
³ Department of Anesthesiology and Intensive Care, Kerckoff-Clinic, Bad Nauheim, Germany.
⁴ Medical Department II, Marien Hospital Herne, Ruhr-University of Bochum, Germany.
⁵ Department of Cardiology, University Hospital Brandenburg, Brandenburg an der Havel, Germany.
⁶ Department of Internal Medicine, University Hospital Ruppin-Brandenburg, Neuruppin, Germany.

Abstract

Background and aim: Atrial fibrosis is an important factor in initiating and maintaining atrial fibrillation (AF). Collagen V belongs to fibrillar collagens. There are, however no data on collagen V in AF. The aim of this work was to study the quantity of collagen V and its relationship with the number of fibroblasts and TGF- b 1 expression in patients in sinus rhythm (SR) and in patients with atrial fibrillation (AF).

Methods: We used quantitative immuhistochemistry to study collagen V in right and left atrial biopsies obtained from 35 patients in SR, 35 patients with paroxysmal AF (pAF) and 27 patients with chronic, long-standing persistent AF (cAF). In addition, we have quantified the number of vimentin-positive fibroblasts and expression levels of TGF-β1.

Results: Compared to patients in SR, collagen V was increased 1.8- and 3.1-fold in patients with pAF and cAF, respectively. In comparison with SR patients, the number of vimentin-positive cells increased significantly 1.46- and 1.8-fold in pAF and cAF patients, respectively.Compared to SR patients, expression levels of TGF-ß1, expressed as fluorescence units per tissue area, was significantly increased by 77 % and 300 % in patients with pAF and cAF, respectively. Similar to intensity measurements, the number of TGFß1-positive cells per 1 mm² atrial tissue increased significantly from 35.5 ± 5.5 cells in SR patients to 61.9 ± 12.4 cells in pAF and 131.5 ± 23.5 cells in cAF. In both types of measurements, there was a statistically significant difference between pAF and cAF groups.

Conclusions: This is the first study to show that AF is associated with increased expression levels of collagen V and TGF-ß1indicating its role in the pathogenesis of atrial fibrosis. In addition, increases in collagen V correlate with increased number of fibroblasts and TGF-β1 and are more pronounced in cAF patients than those in pAF patients.

Keywords: Atrial fibrillation; Collagen V; Fibroblasts; Fibrosis; TGF-β1; Vimentin.