Suppressed Production of Soluble Fms-Like Tyrosine Kinase-1 Contributes to Myocardial Remodeling and Heart Failure.

• Material Type: 博士論文
• Title: Suppressed Production of Soluble Fms-Like Tyrosine Kinase-1 Contributes to Myocardial Remodeling and Heart Failure.
• Author/Editor: Seno, Ayako; Takeda, Yukiji; Matsui, Masaru; Okuda, Aya; Nakano, Tomoya; Nakada, Yasuki; Kumazawa, Takuya; Nakagawa, Hitoshi; Nishida, Taku; Onoue, Kenji; Somekawa, Satoshi; Watanabe, Makoto; Kawata, Hiroyuki; Kawakami, Rika; Okura, Hiroyuki; Uemura, Shiro; Saito, Yoshihiko
• Author Heading: Seno, Ayako; Takeda, Yukiji; Matsui, Masaru; Okuda, Aya; Nakano, Tomoya; Nakada, Yasuki; Kumazawa, Takuya; Nakagawa, Hitoshi; Nishida, Taku; Onoue, Kenji; Somekawa, Satoshi; Watanabe, Makoto; Kawata, Hiroyuki; Kawakami, Rika; Okura, Hiroyuki; Uemura, Shiro; Saito, Yoshihiko
• Publication, Distribution, etc.: American Heart Association / Lippincott, Williams & Wilkins
• Publication Date: 2016-09
• Publication Date (W3CDTF): 2016-09
• Alternative Title: 可溶性Flt-1産生低下は、心筋リモデリングおよび心不全増悪に寄与する
• Periodical title: Hypertension
• No. or year of volume/issue: 68 3
• Volume: 68
• Issue: 3
• Pages: 678-687
• ISSN (Periodical Title): ISSN : 0194-911X
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2016-11-24
• Dissertation Number: 乙第1384号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: chronic kidney disease; heart failure; hypertrophy/remodeling; monocyte chemoattractant protein-1; placental growth factor
• Target Audience: 一般
• Note (General): type:Thesis; Soluble fms-like tyrosine kinase-1 (sFlt-1), an endogenous inhibitor of vascular endothelial growth factor and placental growth factor, is involved in the pathogenesis of cardiovascular disease. However, the significance of sFlt-1 in heart failure has not been fully elucidated. We found that sFlt-1 is decreased in renal failure and serves as a key molecule in atherosclerosis. In this study, we aimed to investigate the role of the decreased sFlt-1 production in heart failure, using sFlt-1 knockout mice. sFlt-1 knockout mice and wild-type mice were subjected to transverse aortic constriction and evaluated after 7 days. The sFlt-1 knockout mice had significantly higher mortality (52% versus 15%; P=0.0002) attributable to heart failure and showed greater cardiac hypertrophy (heart weight to body weight ratio, 8.95±0.45 mg/g in sFlt-1 knockout mice versus 6.60±0.32 mg/g in wild-type mice; P<0.0001) and cardiac dysfunction, which was accompanied by a significant increase in macrophage infiltration and cardiac fibrosis, than wild-type mice after transverse aortic constriction. An anti–placental growth factor–neutralizing antibody prevented pressure overload–induced cardiac hypertrophy, fibrosis, and cardiac dysfunction. Moreover, monocyte chemoattractant protein-1 expression was significantly increased in the hypertrophied hearts of sFlt-1 knockout mice compared with wild-type mice. Monocyte chemoattractant protein-1 inhibition with neutralizing antibody ameliorated maladaptive cardiac remodeling in sFlt-1 knockout mice after transverse aortic constriction. In conclusion, decreased sFlt-1 production plays a key role in the aggravation of cardiac hypertrophy and heart failure through upregulation of monocyte chemoattractant protein-1 expression in pressure-overloaded heart.; 博士（医学）・乙第1384号・平成28年11月24日; © 2016 American Heart Association, Inc.; The definitive version is available at " https://doi.org/10.1161/HYPERTENSIONAHA.116.07371 "; identifier:Hypertension Vol.68 No.3 p.678-687 (2016 Sep); identifier:0194911X; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3289; identifier:Hypertension, 68(3): 678-687
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1161/HYPERTENSIONAHA.116.07371
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU

Table of Contents

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3289/1/01_%e4%b9%991384%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3289/2/02_%e4%b9%991384%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3289/10/03%20%e4%b9%991384%e6%9c%ac%e6%96%87.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3289/11/04%20%e4%b9%991384Figure1-5.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3289/12/05%20%e4%b9%991384Supplementary%20data.pdf fulltext