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  1. 050 医学部, 大学院医学系研究科
  2. 0501 学術論文

LOX-1 Plays an Important Role in Ischemia-Induced Angiogenesis of Limbs

http://hdl.handle.net/10091/00020848
887da08c-062b-4b8e-8197-a0b6dd0e88a6
名前 / ファイル ライセンス アクション
25293063_15.pdf 25293063_15.pdf (731.5 kB)
Item type 学術雑誌論文 / Journal Article(1)
公開日 2018-09-12
タイトル
言語 en
タイトル LOX-1 Plays an Important Role in Ischemia-Induced Angiogenesis of Limbs
言語
言語 eng
資源タイプ
資源 http://purl.org/coar/resource_type/c_6501
タイプ journal article
著者 Shiraki, T

× Shiraki, T

WEKO 106215

en Shiraki, T

Search repository
Aoyama, T

× Aoyama, T

WEKO 106216

en Aoyama, T

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Yokoyama, C

× Yokoyama, C

WEKO 106217

en Yokoyama, C

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Hayakawa, Y

× Hayakawa, Y

WEKO 106218

en Hayakawa, Y

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Tanaka, T

× Tanaka, T

WEKO 106219

en Tanaka, T

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Nishigaki, K

× Nishigaki, K

WEKO 106220

en Nishigaki, K

Search repository
Sawamura, T

× Sawamura, T

WEKO 106221

en Sawamura, T

Search repository
Minatoguchi, S

× Minatoguchi, S

WEKO 106222

en Minatoguchi, S

Search repository
信州大学研究者総覧へのリンク
氏名 Sawamura, Tatsuya
URL http://soar-rd.shinshu-u.ac.jp/profile/ja.HafpjeAF.html
出版者
出版者 PUBLIC LIBRARY SCIENCE
引用
内容記述タイプ Other
内容記述 PLOS ONE.9(12):e114542(2014)
書誌情報 PLOS ONE

巻 9, 号 12, p. e114542, 発行日 2014-12-16
抄録
内容記述タイプ Abstract
内容記述 LOX-1, lectin-like oxidized low-density lipoprotein (LDL) receptor-1, is a single transmembrane receptor mainly expressed on endothelial cells. LOX-1 mediates the uptake of oxidized LDL, an early step in atherosclerosis; however, little is known about whether LOX-1 is involved in angiogenesis during tissue ischemia. Therefore, we examined the role of LOX-1 in ischemia-induced angiogenesis in the hindlimbs of LOX-1 knockout (KO) mice. Angiogenesis was evaluated in a surgically induced hindlimb ischemia model using laser Doppler blood flowmetry (LDBF) and histological capillary density (CD) and arteriole density (AD). After right hindlimb ischemia, the ischemic/nonischemic hindlimb blood flow ratio was persistently lower in LOX-1 KO mice than in wild-type (WT) mice. CD and AD were significantly smaller in LOX-1 KO mice than in WT mice on postoperative day 14. Immunohistochemical analysis revealed that the number of macrophages infiltrating ischemic tissues was significantly smaller in LOX-1 KO mice than in WT mice. The number of infiltrated macrophages expressing VEGF was also significantly smaller in LOX-1 KO mice than in WT mice. Western blot analysis and ROS production assay revealed that LOX- KO mice show significant decrease in Nox2 expression, ROS production and HIF-1α expression, the phosphorylation of p38 MAPK and NF-κB p65 subunit as well as expression of redox-sensitive vascular cell adhesion molecule-1 (VCAM-1) and LOX-1 itself in ischemic muscles, which is supposed to be required for macrophage infiltration expressing angiogenic factor VEGF. Reduction of VEGF expression successively suppressed the phosphorylation of Akt and eNOS, which accelerated angiogenesis, in the ischemic leg of LOX-1 KO mice. Our findings indicate that LOX-1 plays an important role in ischemia-induced angiogenesis by 1) Nox2-ROS-NF-κB activation, 2) upregulated expression of adhesion molecules: VCAM-1 and LOX-1 and 3) promoting macrophage infiltration, which expresses angiogenic factor VEGF.
資源タイプ(コンテンツの種類)
内容記述タイプ Other
内容記述 Article
ISSN
収録物識別子タイプ PISSN
収録物識別子 1932-6203
PubMed
関連識別子
識別子タイプ PMID
関連識別子 https://www.ncbi.nlm.nih.gov/pubmed/25514797
関連名称
関連名称 25514797
DOI
関連識別子
識別子タイプ DOI
関連識別子 https://doi.org/10.1371/journal.pone.0114542
関連名称
関連名称 10.1371/journal.pone.0114542
権利
権利情報 © 2014 Shiraki et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
出版タイプ
出版タイプ VoR
出版タイプResource http://purl.org/coar/version/c_970fb48d4fbd8a85
WoS
表示名 Web of Science
URL http://gateway.isiknowledge.com/gateway/Gateway.cgi?&GWVersion=6&SrcAuth=ShinshuUniv&SrcApp=ShinshuUniv&DestLinkType=FullRecord&DestApp=WOS&KeyUT=000349146300014
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