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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/2699

Title: Suppressed soluble Fms-like tyrosine kinase-1 production aggravates atherosclerosis in chronic kidney disease.
Other Titles: 慢性腎臓病では血中可溶型fms様チロシンキナーゼ-1産生の減少が動脈硬化症を悪化させる
Authors: Matsui, Masaru
Takeda, Yukiji
Uemura, Shiro
Matsumoto, Takaki
Seno, Ayako
Onoue, Kenji
Tsushima, Hideo
Morimoto, Katsuhiko
Soeda, Tsunenari
Okayama, Satoshi
Somekawa, Satoshi
Samejima, Ken-ichi
Kawata, Hiroyuki
Kawakami, Rika
Nakatani, Kimihiko
Iwano, Masayuki
Saito, Yoshihiko
Keywords: atherosclerosis
chronic kidney disease
placental growth factor
soluble fms-like
tyrosine kinase-1
Issue Date: Feb-2014
Publisher: Nature Publishing
Citation: Kidney international Vol.85 No.2 p.393-403
Abstract: Patients with chronic kidney disease (CKD) die of cardiovascular diseases for unknown reasons. Blood vessel formation in plaques and its relationship with plaque stability could be involved with signaling through the Flt-1 receptor and its ligands, vascular endothelial growth factor, and the closely related placental growth factor (PlGF). Flt-1 also exists as a circulating regulatory splice variant short-inhibitory form (sFlt-1) that serves as a decoy receptor, thereby inactivating PlGF. Heparin releases sFlt-1 by displacing the sFlt-1 heparin-binding site from heparin sulfate proteoglycans. Heparin could provide diagnostic inference or could also induce an antiangiogenic state. In the present study, postheparin sFlt-1 levels were lower in CKD patients than in control subjects. More importantly, sFlt-1 levels were inversely related to atherosclerosis in CKD patients, and this correlation was more robust after heparin injection, as verified by subsequent cardiovascular events. Knockout of apolipoprotein E (ApoE) and/or sFlt-1 showed that the absence of sFlt-1 worsened atherogenesis in ApoE-deficient mice. Thus, the relationship between atherosclerosis and PlGF signaling, as regulated by sFlt-1, underscores the underappreciated role of heparin in sFlt-1 release. These clinical and experimental data suggest that novel avenues into CKD-dependent atherosclerosis and its detection are warranted.
Description: 博士(医学)・甲614号・平成26年3月17日
URI: http://hdl.handle.net/10564/2699
ISSN: 00852538
Academic Degrees and number: 24601A614
Degree-granting date: 2014-03-17
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2013年度

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