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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/3289

Title: Suppressed Production of Soluble Fms-Like Tyrosine Kinase-1 Contributes to Myocardial Remodeling and Heart Failure.
Other Titles: 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
Authors: 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
Keywords: chronic kidney disease
heart failure
hypertrophy/remodeling
monocyte chemoattractant protein-1
placental growth factor
Issue Date: Sep-2016
Publisher: American Heart Association / Lippincott, Williams & Wilkins
Citation: Hypertension Vol.68 No.3 p.678-687 (2016 Sep)
Abstract: 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.
Description: 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 "
URI: http://hdl.handle.net/10564/3289
ISSN: 0194911X
Academic Degrees and number: 24601B1384
Degree-granting date: 2016-11-24
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2016年度

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01_乙1384本文の要旨.pdf乙1384本文の要旨240.98 kBAdobe PDFView/Open
02_乙1384審査要旨.pdf乙1384審査要旨670.37 kBAdobe PDFView/Open
03 乙1384本文.pdf乙1384本文656.46 kBAdobe PDFView/Open
04 乙1384Figure1-5.pdf乙1384Figure1-54.88 MBAdobe PDFView/Open
05 乙1384Supplementary data.pdf乙1384Supplementary data1.25 MBAdobe PDFView/Open

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