Accelerated fibrosis and apoptosis with ageing and in atrial fibrillation: Adaptive responses with maladaptive consequences

Xu,Guo-Jun; Gan,Tian-Yi; Tang,Bao-Peng; Chen,Zu-Heng; Mahemuti,Ailiman; Jiang,Tao; Song,Jian-Guo; Guo,Xia; Li,Yao-Dong; Miao,Hai-Jun; Zhou,Xian-Hui; Zhang,Yu; Li,Jin-Xin

doi:10.3892/etm.2013.899

Accelerated fibrosis and apoptosis with ageing and in atrial fibrillation: Adaptive responses with maladaptive consequences

Authors:
- Guo-Jun Xu
- Tian-Yi Gan
- Bao-Peng Tang
- Zu-Heng Chen
- Ailiman Mahemuti
- Tao Jiang
- Jian-Guo Song
- Xia Guo
- Yao-Dong Li
- Hai-Jun Miao
- Xian-Hui Zhou
- Yu Zhang
- Jin-Xin Li
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Affiliations: Department of Cardiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China, Department of Animal Experiment, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China, Department of Electrophysiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China, Department of Molecular Biology, Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China
Published online on: January 16, 2013 https://doi.org/10.3892/etm.2013.899
Pages: 723-729

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Abstract

The aim of this study was to investigate whether abnormal expression of matrix metalloproteinase (MMP)-9/tissue inhibitors of MMPs (TIMP)-1 and B cell lymphoma 2 (BCL-2)/BCL-2-associated X protein (BAX) are correlated with the characteristic accelerated fibrosis and apoptosis during ageing and in atrial fibrillation (AF). Four groups of dogs were studied: adult dogs in sinus rhythm (SR), aged dogs in SR, adult dogs with AF induced by rapid atrial pacing and aged dogs with AF induced by rapid atrial pacing. The mRNA and protein expression levels of the target gene in the left atrium were measured by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis. Pathohistological and ultrastructural changes were assessed by light and electron microscopy. The apoptotic indices of myocytes were detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL). The mRNA and protein expression levels of MMP-9 and BAX and those of TIMP-1 and BCL-2 were significantly upregulated and downregulated, respectively, in the aged groups compared with the adult groups. Compared with the control groups, the adult and aged groups with AF exhibited significantly increased mRNA and protein expression levels of MMP-9 and BAX and decreased expression levels of TIMP-1 and BCL-2. Samples of atrial tissue demonstrated abnormal pathohistological and ultrastructural changes, accelerated fibrosis and apoptosis. MMP-9/TIMP-1 and BCL-2/BAX hold potential for use as substrates conducive to AF and their abnormal expression plays a major role in structural remodeling of the atrium.

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