Clinical Research Papers:

Gender differences in fibrosis remodeling in patients with long-standing persistent atrial fibrillation

Zhi Li, Zengwei Wang, Zongtao Yin, Yuji Zhang, Xiaodong Xue, Jinsong Han, Yan Zhu, Jian Zhang, Maximilian Y. Emmert and Huishan Wang _

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Oncotarget. 2017; 8:53714-53729. https://doi.org/10.18632/oncotarget.16342

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Zhi Li1, Zengwei Wang1, Zongtao Yin1, Yuji Zhang1, Xiaodong Xue1, Jinsong Han1, Yan Zhu1, Jian Zhang1, Maximilian Y. Emmert2 and Huishan Wang1

1 Department of Cardiovascular Surgery, Shenyang Northern Hospital, Shenyang, China

2 Clinic for Cardiovascular Surgery, University Hospital Zurich, Rämistrasse, Zürich, Switzerland

Correspondence to:

Huishan Wang, email:

Maximilian Y. Emmert, email:

Keywords: gender differences; atrial fibrillation; remodeling; mitral valve; pulmonary vein

Received: November 07, 2016 Accepted: February 06, 2017 Published: March 17, 2017


The success rate of catheter ablation in atrial fibrillation (AF) is known to be lower in females than in males. However, while the exact mechanism for this phenomenon remains to be elucidated, tissue fibrosis may play an important role in this regard. It has been shown that fibrosis promotes AF and its recurrence, thereby substantially reducing the efficacy of catheter ablation in AF patients. Thus, we hypothesized that fibrosis may contribute to gender differences in the outcomes of AF catheter ablation.

Here we systematically assessed pulmonary vein sleeves obtained from 166 patients with and without long-standing persistent-AF (LSP-AF) in order to identify gender-specific mechanistic differences in fibrosis remodeling of AF patients.

Histological analysis revealed that the female LSP-AF group, rather than its male counterpart, had a higher degree of fibrosis when compared to the NON-AF group. Further analysis using microarray, immunohistochemistry and Western Blot displayed that gender differences in fibrosis remodeling of LSP-AF were mainly due to the inherent differential expression of fibrosis-related genes (n=32) and proteins (n=6). Especially, those related to the TGFβ/Smad3 pathway appeared to be up-regulated in the female LSP-AF group thus promoting an aggravation of fibrosis remodeling. In summary, our data suggest that the aggravation of fibrosis remodeling in women may be an important reason for the low success rate of AF catheter ablation when compared to men. Therefore, inhibiting the TGFβ/Smad3 pathway-mediated fibrosis could represent an interesting target for future therapeutic concepts to improve the success rate of AF catheter ablation in women.

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