論文

基本情報

氏名 新井 しのぶ
氏名(カナ) アライ シノブ
氏名(英語) ARAI SHINOBU
所属 中村学園大学 教育学部 児童幼児教育学科
職名 講師

題名

Twinkle overexpression prevents cardiac rupture after myocardial infarction by alleviating impaired mitochondrial biogenesis

単著・共著の別

 

著者

Takahiro Inoue
Masataka Ikeda
Tomomi Ide
Takeo Fujino
Yuka Matsuo
Shinobu Arai
Keita Saku
Kenji Sunagawa

担当区分

 

概要

Cardiac rupture is a fatal complication after myocardial infarction (MI). However, the detailed mechanism underlying cardiac rupture after MI remains to be fully elucidated. In this study, we investigated the role of mitochondrial DNA (mtDNA) and mitochondria in the pathophysiology of cardiac rupture by analyzing Twinkle helicase overexpression mice (TW mice). Twinkle overexpression increased mtDNA copy number approximately twofold and ameliorated ischemic cardiomyopathy at day 28 after MI. Notably, Twinkle overexpression markedly prevented cardiac rupture and improved post-MI survival, accompanied by the suppression of MMP-2 and MMP-9 in the MI border area at day 5 after MI when cardiac rupture frequently occurs. Additionally, these cardioprotective effects of Twinkle overexpression were abolished in transgenic mice overexpressing mutant Twinkle with an in-frame duplication of amino acids 353-365, which resulted in no increases in mtDNA copy number. Furthermore, although apoptosis and oxidative stress were induced and mitochondria were damaged in the border area, these injuries were improved in TW mice. Further analysis revealed that mitochondrial biogenesis, including mtDNA copy number, transcription, and translation, was severely impaired in the border area at day 5. In contrast, Twinkle overexpression maintained mtDNA copy number and restored the impaired transcription and translation of mtDNA in the border area. These results demonstrated that Twinkle overexpression alleviated impaired mitochondrial biogenesis in the border area through maintained mtDNA copy number and thereby prevented cardiac rupture accompanied by the reduction of apoptosis and oxidative stress, and suppression of MMP activity.

発表雑誌等の名称

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY

出版者

AMER PHYSIOLOGICAL SOC

311

3

開始ページ

H509

終了ページ

H519

発行又は発表の年月

2016-09

査読の有無

有り

招待の有無

無し

記述言語

英語

掲載種別

研究論文(学術雑誌)

国際・国内誌

 

国際共著

 

ISSN

 

eISSN

 

DOI

10.1152/ajpheart.00044.2016

Cinii Articles ID

 

Cinii Books ID

 

Pubmed ID

 

PubMed Central 記事ID

 

形式

無償ダウンロード

JGlobalID

 

arXiv ID

 

ORCIDのPut Code

 

DBLP ID