Midkine promotes atherosclerotic plaque formation through its pro-inflammatory, angiogenic and anti-apoptotic functions in apolipoprotein E-knockout mice

Yoshio Takemoto, Mitsuru Horiba, Masahide Harada, Kazuma Sakamoto, Kyosuke Takeshita, Toyoaki Murohara, Kenji Kadomatsu, Kaichiro Kamiya

研究成果: Article

2 引用 (Scopus)

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Background: A recent study suggested that midkine (MK), a heparin-binding growth factor, is associated with atherosclerosis progression in patients with artery disease. It has previously been reported that MK plays a critical role in neointima formation in a restenosis model, whereas the role of MK in the development of atherosclerosis has not been investigated. The present study assessed the effect of MK administration on the process of atherosclerotic plaque formation in apolipoprotein E-knockout (ApoE −/− ) mice. Methods and Results: Using an osmotic pump, human recombinant MK protein was intraperitoneally administered for 12 weeks in C57BL/6 ApoE −/− (ApoE −/− -MK) and ApoE +/+ mice fed a high-fat diet. Saline was administered to the control groups of ApoE −/− (ApoE −/− -saline) and ApoE +/+ mice. The atherosclerotic lesion areas in longitudinal aortic sections were significantly larger in ApoE −/− -MK mice than in ApoE −/− -saline mice. The aortic mRNA levels of pro-inflammatory and angiogenic factors, and the percentage of macrophages in aortic root lesions, were significantly higher in ApoE −/− -MK mice than in ApoE −/− -saline mice, whereas the percentage of apoptotic cells was significantly lower in ApoE −/− -MK mice than in ApoE −/− -saline mice. Conclusions: The systemic administration of MK in ApoE −/− mice promoted atherosclerotic plaque formation through pro-inflammatory, angiogenic, and anti-apoptotic effects. MK may serve as a potential therapeutic target for the prevention of atherosclerosis under atherogenic conditions.

元の言語English
ページ(範囲)19-27
ページ数9
ジャーナルCirculation Journal
82
発行部数1
DOI
出版物ステータスPublished - 01-01-2018

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Apolipoproteins E
Atherosclerotic Plaques
Knockout Mice
Atherosclerosis
midkine
Neointima
Angiogenesis Inducing Agents
High Fat Diet
Recombinant Proteins
Heparin
Intercellular Signaling Peptides and Proteins
Arteries

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

これを引用

Takemoto, Yoshio ; Horiba, Mitsuru ; Harada, Masahide ; Sakamoto, Kazuma ; Takeshita, Kyosuke ; Murohara, Toyoaki ; Kadomatsu, Kenji ; Kamiya, Kaichiro. / Midkine promotes atherosclerotic plaque formation through its pro-inflammatory, angiogenic and anti-apoptotic functions in apolipoprotein E-knockout mice. :: Circulation Journal. 2018 ; 巻 82, 番号 1. pp. 19-27.
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title = "Midkine promotes atherosclerotic plaque formation through its pro-inflammatory, angiogenic and anti-apoptotic functions in apolipoprotein E-knockout mice",
abstract = "Background: A recent study suggested that midkine (MK), a heparin-binding growth factor, is associated with atherosclerosis progression in patients with artery disease. It has previously been reported that MK plays a critical role in neointima formation in a restenosis model, whereas the role of MK in the development of atherosclerosis has not been investigated. The present study assessed the effect of MK administration on the process of atherosclerotic plaque formation in apolipoprotein E-knockout (ApoE −/− ) mice. Methods and Results: Using an osmotic pump, human recombinant MK protein was intraperitoneally administered for 12 weeks in C57BL/6 ApoE −/− (ApoE −/− -MK) and ApoE +/+ mice fed a high-fat diet. Saline was administered to the control groups of ApoE −/− (ApoE −/− -saline) and ApoE +/+ mice. The atherosclerotic lesion areas in longitudinal aortic sections were significantly larger in ApoE −/− -MK mice than in ApoE −/− -saline mice. The aortic mRNA levels of pro-inflammatory and angiogenic factors, and the percentage of macrophages in aortic root lesions, were significantly higher in ApoE −/− -MK mice than in ApoE −/− -saline mice, whereas the percentage of apoptotic cells was significantly lower in ApoE −/− -MK mice than in ApoE −/− -saline mice. Conclusions: The systemic administration of MK in ApoE −/− mice promoted atherosclerotic plaque formation through pro-inflammatory, angiogenic, and anti-apoptotic effects. MK may serve as a potential therapeutic target for the prevention of atherosclerosis under atherogenic conditions.",
author = "Yoshio Takemoto and Mitsuru Horiba and Masahide Harada and Kazuma Sakamoto and Kyosuke Takeshita and Toyoaki Murohara and Kenji Kadomatsu and Kaichiro Kamiya",
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Midkine promotes atherosclerotic plaque formation through its pro-inflammatory, angiogenic and anti-apoptotic functions in apolipoprotein E-knockout mice. / Takemoto, Yoshio; Horiba, Mitsuru; Harada, Masahide; Sakamoto, Kazuma; Takeshita, Kyosuke; Murohara, Toyoaki; Kadomatsu, Kenji; Kamiya, Kaichiro.

:: Circulation Journal, 巻 82, 番号 1, 01.01.2018, p. 19-27.

研究成果: Article

TY - JOUR

T1 - Midkine promotes atherosclerotic plaque formation through its pro-inflammatory, angiogenic and anti-apoptotic functions in apolipoprotein E-knockout mice

AU - Takemoto, Yoshio

AU - Horiba, Mitsuru

AU - Harada, Masahide

AU - Sakamoto, Kazuma

AU - Takeshita, Kyosuke

AU - Murohara, Toyoaki

AU - Kadomatsu, Kenji

AU - Kamiya, Kaichiro

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: A recent study suggested that midkine (MK), a heparin-binding growth factor, is associated with atherosclerosis progression in patients with artery disease. It has previously been reported that MK plays a critical role in neointima formation in a restenosis model, whereas the role of MK in the development of atherosclerosis has not been investigated. The present study assessed the effect of MK administration on the process of atherosclerotic plaque formation in apolipoprotein E-knockout (ApoE −/− ) mice. Methods and Results: Using an osmotic pump, human recombinant MK protein was intraperitoneally administered for 12 weeks in C57BL/6 ApoE −/− (ApoE −/− -MK) and ApoE +/+ mice fed a high-fat diet. Saline was administered to the control groups of ApoE −/− (ApoE −/− -saline) and ApoE +/+ mice. The atherosclerotic lesion areas in longitudinal aortic sections were significantly larger in ApoE −/− -MK mice than in ApoE −/− -saline mice. The aortic mRNA levels of pro-inflammatory and angiogenic factors, and the percentage of macrophages in aortic root lesions, were significantly higher in ApoE −/− -MK mice than in ApoE −/− -saline mice, whereas the percentage of apoptotic cells was significantly lower in ApoE −/− -MK mice than in ApoE −/− -saline mice. Conclusions: The systemic administration of MK in ApoE −/− mice promoted atherosclerotic plaque formation through pro-inflammatory, angiogenic, and anti-apoptotic effects. MK may serve as a potential therapeutic target for the prevention of atherosclerosis under atherogenic conditions.

AB - Background: A recent study suggested that midkine (MK), a heparin-binding growth factor, is associated with atherosclerosis progression in patients with artery disease. It has previously been reported that MK plays a critical role in neointima formation in a restenosis model, whereas the role of MK in the development of atherosclerosis has not been investigated. The present study assessed the effect of MK administration on the process of atherosclerotic plaque formation in apolipoprotein E-knockout (ApoE −/− ) mice. Methods and Results: Using an osmotic pump, human recombinant MK protein was intraperitoneally administered for 12 weeks in C57BL/6 ApoE −/− (ApoE −/− -MK) and ApoE +/+ mice fed a high-fat diet. Saline was administered to the control groups of ApoE −/− (ApoE −/− -saline) and ApoE +/+ mice. The atherosclerotic lesion areas in longitudinal aortic sections were significantly larger in ApoE −/− -MK mice than in ApoE −/− -saline mice. The aortic mRNA levels of pro-inflammatory and angiogenic factors, and the percentage of macrophages in aortic root lesions, were significantly higher in ApoE −/− -MK mice than in ApoE −/− -saline mice, whereas the percentage of apoptotic cells was significantly lower in ApoE −/− -MK mice than in ApoE −/− -saline mice. Conclusions: The systemic administration of MK in ApoE −/− mice promoted atherosclerotic plaque formation through pro-inflammatory, angiogenic, and anti-apoptotic effects. MK may serve as a potential therapeutic target for the prevention of atherosclerosis under atherogenic conditions.

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