Effect of eicosapentaenoic acid and pitavastatin on electrophysiology and anticoagulant gene expression in mice with rapid atrial pacing

Maoqing Tong, Jiewen Wang, Yunxin Ji, Xiaomin Chen, Jieru Wang, Shuangshuang Wang, Liemin Ruan, Hanbin Cui, Ying Zhou, Qingyu Zhang, Eiichi Watanabe

Research output: Contribution to journalArticle

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Abstract

Atrial remodeling is considered to be any persistent change in atrial structure or function, and is responsible for the development and perpetuation of atrial fibrillation (AF). Oxidative stress and intracellular pH regulation may also be linked to AF; however it remains unclear whether eicosapentaenoic acid (EPA) or statins have beneficial therapeutic effects. The aim of the present study was to investigate the effects of EPA and pitavastatin on the electrophysiology of and gene expressions in mice with rapidly-paced atria. Mice were treated with EPA (10 mg/g/day) or pitavastatin (30 ng/g/day) for 6 weeks, following which AF was simulated by 8-h atrial pacing at 1,800 bpm. The atrial electrophysiological properties and the expression of cardiac genes, potassium voltage-gated channel subfamily A member 5 (Kcna5), Kcn subfamily D member 2 (Kcnd2), Kv channel-interacting protein 2 (KChIP2), solute carrier family 9 member A1, thrombomodulin (TM) and tissue factor pathway inhibitor (TFPI) were examined using reverse transcription-quantitative polymerase chain reaction. In control mice, significant atrial electrical remodeling was observed (P<0.05); however, treatment with either EPA or pitavastatin ameliorated these electrophysiological changes (P>0.05). mRNA levels of Kcnd2, KChIP2 and Kcna5 were significantly upregulated in control mice (P<0.05), whereas treatment with EPA or pitavastatin attenuated this upregulation (P>0.05). Administration of pitavastatin significantly reduced the downregulation of both TFPI andTM (P<0.05). EPA treatment attenuated the TFPI downregulation compared with control mice (P>0.05), however no significant effect onTM expression was observed. In addition, both EPA (P>0.05) and pitavastatin (P<0.05) suppressed the overexpression of endothelial nitric oxide synthase. This was also exhibited in Ras-related C3 botulinum toxin substrate 1 genes (P<0.01 for both treatments). In conclusion, the results of the present study suggested that EPA and pitavastatin are able to prevent atrial electrical remodeling, thrombotic states and oxidative stress in rapidly-paced murine atria.

Original languageEnglish
Pages (from-to)2310-2316
Number of pages7
JournalExperimental and Therapeutic Medicine
Volume14
Issue number3
DOIs
Publication statusPublished - 01-01-2017

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Atrial Remodeling
Eicosapentaenoic Acid
Electrophysiology
Anticoagulants
Kv Channel-Interacting Proteins
Gene Expression
Atrial Fibrillation
rac1 GTP-Binding Protein
Oxidative Stress
Voltage-Gated Potassium Channels
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Thrombomodulin
Nitric Oxide Synthase Type III
Therapeutic Uses
Reverse Transcription
Down-Regulation
pitavastatin
Polymerase Chain Reaction
Messenger RNA
Genes

All Science Journal Classification (ASJC) codes

  • Immunology and Microbiology (miscellaneous)
  • Cancer Research

Cite this

Tong, Maoqing ; Wang, Jiewen ; Ji, Yunxin ; Chen, Xiaomin ; Wang, Jieru ; Wang, Shuangshuang ; Ruan, Liemin ; Cui, Hanbin ; Zhou, Ying ; Zhang, Qingyu ; Watanabe, Eiichi. / Effect of eicosapentaenoic acid and pitavastatin on electrophysiology and anticoagulant gene expression in mice with rapid atrial pacing. In: Experimental and Therapeutic Medicine. 2017 ; Vol. 14, No. 3. pp. 2310-2316.
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abstract = "Atrial remodeling is considered to be any persistent change in atrial structure or function, and is responsible for the development and perpetuation of atrial fibrillation (AF). Oxidative stress and intracellular pH regulation may also be linked to AF; however it remains unclear whether eicosapentaenoic acid (EPA) or statins have beneficial therapeutic effects. The aim of the present study was to investigate the effects of EPA and pitavastatin on the electrophysiology of and gene expressions in mice with rapidly-paced atria. Mice were treated with EPA (10 mg/g/day) or pitavastatin (30 ng/g/day) for 6 weeks, following which AF was simulated by 8-h atrial pacing at 1,800 bpm. The atrial electrophysiological properties and the expression of cardiac genes, potassium voltage-gated channel subfamily A member 5 (Kcna5), Kcn subfamily D member 2 (Kcnd2), Kv channel-interacting protein 2 (KChIP2), solute carrier family 9 member A1, thrombomodulin (TM) and tissue factor pathway inhibitor (TFPI) were examined using reverse transcription-quantitative polymerase chain reaction. In control mice, significant atrial electrical remodeling was observed (P<0.05); however, treatment with either EPA or pitavastatin ameliorated these electrophysiological changes (P>0.05). mRNA levels of Kcnd2, KChIP2 and Kcna5 were significantly upregulated in control mice (P<0.05), whereas treatment with EPA or pitavastatin attenuated this upregulation (P>0.05). Administration of pitavastatin significantly reduced the downregulation of both TFPI andTM (P<0.05). EPA treatment attenuated the TFPI downregulation compared with control mice (P>0.05), however no significant effect onTM expression was observed. In addition, both EPA (P>0.05) and pitavastatin (P<0.05) suppressed the overexpression of endothelial nitric oxide synthase. This was also exhibited in Ras-related C3 botulinum toxin substrate 1 genes (P<0.01 for both treatments). In conclusion, the results of the present study suggested that EPA and pitavastatin are able to prevent atrial electrical remodeling, thrombotic states and oxidative stress in rapidly-paced murine atria.",
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Effect of eicosapentaenoic acid and pitavastatin on electrophysiology and anticoagulant gene expression in mice with rapid atrial pacing. / Tong, Maoqing; Wang, Jiewen; Ji, Yunxin; Chen, Xiaomin; Wang, Jieru; Wang, Shuangshuang; Ruan, Liemin; Cui, Hanbin; Zhou, Ying; Zhang, Qingyu; Watanabe, Eiichi.

In: Experimental and Therapeutic Medicine, Vol. 14, No. 3, 01.01.2017, p. 2310-2316.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effect of eicosapentaenoic acid and pitavastatin on electrophysiology and anticoagulant gene expression in mice with rapid atrial pacing

AU - Tong, Maoqing

AU - Wang, Jiewen

AU - Ji, Yunxin

AU - Chen, Xiaomin

AU - Wang, Jieru

AU - Wang, Shuangshuang

AU - Ruan, Liemin

AU - Cui, Hanbin

AU - Zhou, Ying

AU - Zhang, Qingyu

AU - Watanabe, Eiichi

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Atrial remodeling is considered to be any persistent change in atrial structure or function, and is responsible for the development and perpetuation of atrial fibrillation (AF). Oxidative stress and intracellular pH regulation may also be linked to AF; however it remains unclear whether eicosapentaenoic acid (EPA) or statins have beneficial therapeutic effects. The aim of the present study was to investigate the effects of EPA and pitavastatin on the electrophysiology of and gene expressions in mice with rapidly-paced atria. Mice were treated with EPA (10 mg/g/day) or pitavastatin (30 ng/g/day) for 6 weeks, following which AF was simulated by 8-h atrial pacing at 1,800 bpm. The atrial electrophysiological properties and the expression of cardiac genes, potassium voltage-gated channel subfamily A member 5 (Kcna5), Kcn subfamily D member 2 (Kcnd2), Kv channel-interacting protein 2 (KChIP2), solute carrier family 9 member A1, thrombomodulin (TM) and tissue factor pathway inhibitor (TFPI) were examined using reverse transcription-quantitative polymerase chain reaction. In control mice, significant atrial electrical remodeling was observed (P<0.05); however, treatment with either EPA or pitavastatin ameliorated these electrophysiological changes (P>0.05). mRNA levels of Kcnd2, KChIP2 and Kcna5 were significantly upregulated in control mice (P<0.05), whereas treatment with EPA or pitavastatin attenuated this upregulation (P>0.05). Administration of pitavastatin significantly reduced the downregulation of both TFPI andTM (P<0.05). EPA treatment attenuated the TFPI downregulation compared with control mice (P>0.05), however no significant effect onTM expression was observed. In addition, both EPA (P>0.05) and pitavastatin (P<0.05) suppressed the overexpression of endothelial nitric oxide synthase. This was also exhibited in Ras-related C3 botulinum toxin substrate 1 genes (P<0.01 for both treatments). In conclusion, the results of the present study suggested that EPA and pitavastatin are able to prevent atrial electrical remodeling, thrombotic states and oxidative stress in rapidly-paced murine atria.

AB - Atrial remodeling is considered to be any persistent change in atrial structure or function, and is responsible for the development and perpetuation of atrial fibrillation (AF). Oxidative stress and intracellular pH regulation may also be linked to AF; however it remains unclear whether eicosapentaenoic acid (EPA) or statins have beneficial therapeutic effects. The aim of the present study was to investigate the effects of EPA and pitavastatin on the electrophysiology of and gene expressions in mice with rapidly-paced atria. Mice were treated with EPA (10 mg/g/day) or pitavastatin (30 ng/g/day) for 6 weeks, following which AF was simulated by 8-h atrial pacing at 1,800 bpm. The atrial electrophysiological properties and the expression of cardiac genes, potassium voltage-gated channel subfamily A member 5 (Kcna5), Kcn subfamily D member 2 (Kcnd2), Kv channel-interacting protein 2 (KChIP2), solute carrier family 9 member A1, thrombomodulin (TM) and tissue factor pathway inhibitor (TFPI) were examined using reverse transcription-quantitative polymerase chain reaction. In control mice, significant atrial electrical remodeling was observed (P<0.05); however, treatment with either EPA or pitavastatin ameliorated these electrophysiological changes (P>0.05). mRNA levels of Kcnd2, KChIP2 and Kcna5 were significantly upregulated in control mice (P<0.05), whereas treatment with EPA or pitavastatin attenuated this upregulation (P>0.05). Administration of pitavastatin significantly reduced the downregulation of both TFPI andTM (P<0.05). EPA treatment attenuated the TFPI downregulation compared with control mice (P>0.05), however no significant effect onTM expression was observed. In addition, both EPA (P>0.05) and pitavastatin (P<0.05) suppressed the overexpression of endothelial nitric oxide synthase. This was also exhibited in Ras-related C3 botulinum toxin substrate 1 genes (P<0.01 for both treatments). In conclusion, the results of the present study suggested that EPA and pitavastatin are able to prevent atrial electrical remodeling, thrombotic states and oxidative stress in rapidly-paced murine atria.

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