Pioglitazone Attenuates Inflammatory Atrial Fibrosis and Vulnerability to Atrial Fibrillation Induced by Pressure Overload in Rats
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- Kume Osamu
- Department of Internal Medicine 1, Oita University
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- Takahashi Naohiko
- Department of Laboratory Examination and Diagnostics, Oita University
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- Wakisaka Osamu
- Department of Internal Medicine 1, Oita University
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- Nagano-Torigoe Yasuko
- Department of Laboratory Examination and Diagnostics, Oita University
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- Teshima Yasushi
- Department of Laboratory Examination and Diagnostics, Oita University
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- Nakagawa Mikiko
- Department of Laboratory Examination and Diagnostics, Oita University
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- Yufu Kunio
- Department of Laboratory Examination and Diagnostics, Oita University
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- Hara Masahide
- Department of Internal Medicine 1, Oita University
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- Saikawa Tetsunori
- Department of Laboratory Examination and Diagnostics, Oita University
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- Yoshimatsu Hironobu
- Department of Internal Medicine 1, Oita University
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Background: Inflammatory processes are involved in the pathogenesis of atrial fibrillation (AF).<BR>Objective: The purpose of this study was to test the hypothesis that atrial fibrosis and enhanced vulnerability to AF evoked by pressure overload can be attenuated by pioglitazone, a peroxisome proliferator-activated receptor-γ agonist, via suppression of inflammatory profibrotic signals.<BR>Methods: Male Sprague-Dawley rats were subjected to abdominal aortic constriction (AAC). Pioglitazone 3 mg/kg/day or vehicle was orally administered for 4 weeks.<BR>Results: Western blot analysis revealed that AAC enhanced expression of monocyte chemoattractant protein (MCP)-1, transforming growth factor-β1 and α-smooth muscle actin in the left atrium (LA), which was suppressed by pioglitazone. Messenger RNA expression of collagen type 1 and atrial natriuretic peptide in the LA was increased by AAC, which was suppressed by pioglitazone. Gelatin zymography demonstrated that activity of matrix metalloproteinase-9 was increased by AAC, which was suppressed by pioglitazone. Pioglitazone attenuated AAC-induced LA fibrosis. In isolated-perfused heart experiments, AAC did not alter the refractory period of the LA or the right atrium (RA), but it did prolong the interatrial conduction time. Programmed extrastimuli from the RA induced AF in all of the AAC-treated rats (8/8 [100%]). This was suppressed by pioglitazone (2/8 [25%], P<.05) with normalization to interatrial conduction time.<BR>Conclusion: The results of this study suggest that inflammatory profibrotic mechanisms are involved in this pressure-overloaded AF model. The results also suggest that pioglitazone is effective at attenuating atrial fibrosis, possibly via suppression of MCP-1-mediated inflammatory profibrotic processes.
収録刊行物
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- Journal of Arrhythmia
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Journal of Arrhythmia 27 (Supplement), JAAC_1-, 2011
日本不整脈学会
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詳細情報 詳細情報について
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- CRID
- 1390001205246175360
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- NII論文ID
- 130002130407
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- ISSN
- 18832148
- 18804276
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- Crossref
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可