Suppressed soluble Fms-like tyrosine kinase-1 production aggravates atherosclerosis in chronic kidney disease.

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.;博士(医学)・甲614号・平成26年3月17日;開始ページ : 393;終了ページ : 403;PubMed番号 : http://www.ncbi.nlm.nih.gov/pubmed/24048373

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書名 Suppressed soluble Fms-like tyrosine kinase-1 production aggravates atherosclerosis in chronic kidney disease.
著作者等 International Society of Nephrology
Iwano Masayuki
Kawakami Rika
Kawata Hiroyuki
Matsumoto Takaki
Morimoto Katsuhiko
Nakatani Kimihiko
Okayama Satoshi
Onoue Kenji
Saito Yoshihiko
Samejima Ken-ichi
Seno Ayako
Soeda Tsunenari
Somekawa Satoshi
Takeda Yukiji
Tsushima Hideo
Uemura Shiro
Matsui Masaru
書名別名 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
出版元 Nature
刊行年月 1974-2011
ページ数 v.
大きさ 28 cm
ISSN 00852538
NCID AA00711004
AA00710996
※クリックでCiNii Booksを表示
言語 英語
出版国 アメリカ合衆国
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