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From changes in local RAAS to structural remodeling of the left atrium

A beautiful cycle in atrial fibrillation

Von Veränderungen im lokalen RAAS zum strukturellen Remodeling des linken Vorhofs

Ein positiver Kreislauf bei Vorhofflimmern

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Abstract

Aims

In earlier studies, we reported structural remodeling was associated with atrial fibrillation (AF) and showed that the renin–angiotensin–aldosterone system (RAAS) was linked to AF. It is reasonable to hypothesize that there is a cycle, from RAAS to structural remodeling to AF.

Patients and methods

Our study group consisted of 80 patients scheduled for mitral valve replacement surgery. Tissue samples of the left atrial appendages were obtained. Masson’s trichrome staining and immunohistochemical staining were performed to assess the extent of fibrosis. Radioimmunoassay was carried out to investigate the expression levels of local RAAS. RAAS-related genes were analyzed by RT-PCR.

Results

There was a significantly increased degree of fibrosis in AF patients compared with sinus rhythm (SR) patients (p = 0.023). There were significant differences in the expression levels of local angiotensin (Ang) II between the SR and the AF groups (p = 0.002). The expression levels of local Ang II correlated with the duration of AF (r = 0.727851, p = 0.001) and with collagen type I (r = 0.672189, p = 0.032). In the AF group, the mRNA expressions of the AT1R and ACE genes were markedly up-regulated in comparison with the SR group (p = 0.021 and p = 0.037).

Conclusions

On the basis of this study, and in combination with results of our previous studies, we demonstrate for the first time that there is a cycle involving RAAS, structural remodeling, and AF. RAAS, structural remodeling, and AF are the principal aspects in this cycle.

Zusammenfassung

Ziele

In einer vorherigen Studie berichteten die Autoren über strukturelles Remodeling in Zusammenhang mit Vorhofflimmern (VF). In einer anderen Studie zeigten die Autoren, dass das Renin-Angiotensin-Aldosteron-System (RAAS) mit VF in Zusammenhang steht. Es ist begründet, die Hypothese aufzustellen, dass es einen Kreislauf vom RAAS über strukturelles Remodeling bis zum VF gebe.

Methoden

Die Studiengruppe bestand aus 80 Patienten, bei denen eine Operation zum Mitralklappenersatz vorgesehen war. Gewebeproben wurden aus dem linken Herzohr entnommen. Die Masson-Trichromfärbung und eine immunhistochemische Färbung wurden durchgeführt, um das Ausmaß der Fibrose zu ermitteln. Die Bestimmung der Expression des lokalen RAAS erfolgte mit einem Radioimmunoassay. Die RAAS-bezogenen Gene wurden mittels RT-PCR analysiert.

Ergebnisse

Das Ausmaß der Fibrose wies eine signifikante Zunahme bei VF-Patienten gegenüber Patienten mit Sinusrhythmus (SR) auf (p = 0,023). Es bestanden signifikante Unterschiede bei der Expression von lokalem Angiotensin II (Ang II) zwischen der Gruppe mit SR und der Gruppe mit VF (p = 0,002). Die Expression von lokalem Ang II korrelierte mit der Dauer des VF (r = 0,727851; p = 0,001) und mit Kollagen vom Typ I (r = 0,672189; p = 0,032). In der Gruppe mit VF war die mRNA-Expression des AT1R- und ACE-Gens deutlich hochreguliert im Vergleich zu der Gruppe mit SR (p = 0,021 bzw. p = 0,037).

Schlussfolgerungen

Gemäß der vorliegenden Studie und in Kombination mit den vorhergehenden Studien wurde hier erstmals gezeigt, dass es einen Kreislauf zwischen RAAS, strukturellem Remodeling und VF gibt. RAAS, strukturelles Remodeling und VF sind die grundlegenden, wesentlichen Aspekte dieses Kreislaufs.

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Acknowledgments

We thank all the personnel of the echocardiography department and the laboratory of experimental medicine for their collaboration throughout this study. The authors would like to thank Dr. Adam P. Allen for his editorial and review assistance. This work was supported by grants from the Specialized Research Fund for the Doctoral Program of Higher Education, PCR (Grant No. 20120181120041), and the Science and Technology Bureau of Chengdu, Sichuan Province, PRC (Grant No. 12PPYB192SF-002).

Compliance with ethical guidelines

Conflict of interest. Q. Yongjun, S. Huanzhang, Z. Wenxia, T. Hong, and X. Xijun state that there are no conflicts of interest. All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients included in studies.

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Authors and Affiliations

  1. Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, China

    Q. Yongjun, S. Huanzhang & X. Xijun

  2. Department of Critical Care Medicine, Henan Provincial People’s Hospital, Zhengzhou, China

    S. Huanzhang

  3. Department of Cardiology, West China Hospital, Sichuan University, 610041, Chengdu, China

    Z. Wenxia & T. Hong

Authors
  1. Q. Yongjun
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  2. S. Huanzhang
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  3. Z. Wenxia
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  4. T. Hong
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  5. X. Xijun
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Corresponding author

Correspondence to X. Xijun.

Additional information

Qian Yongjun and Shao Huanzhang contributed equally to this study.

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Yongjun, Q., Huanzhang, S., Wenxia, Z. et al. From changes in local RAAS to structural remodeling of the left atrium. Herz 40, 514–520 (2015). https://doi.org/10.1007/s00059-013-4032-7

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  • DOI: https://doi.org/10.1007/s00059-013-4032-7

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