Midkine Promotes Atherosclerotic Plaque Formation Through Its Pro-Inflammatory, Angiogenic and Anti-Apoptotic Functions in Apolipoprotein E-Knockout Mice

DOI Web Site Web Site PubMed 1 Citations 42 References
  • Takemoto Yoshio
    Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital
  • Horiba Mitsuru
    Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University Department of Biochemistry, Nagoya University Graduate School of Medicine Suizawa Hospital
  • Harada Masahide
    Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University Department of Cardiology, Fujita Health University
  • Sakamoto Kazuma
    Department of Biochemistry, Nagoya University Graduate School of Medicine
  • Takeshita Kyosuke
    Department of Cardiology, Nagoya University Graduate School of Medicine
  • Murohara Toyoaki
    Department of Cardiology, Nagoya University Graduate School of Medicine
  • Kadomatsu Kenji
    Department of Biochemistry, Nagoya University Graduate School of Medicine
  • Kamiya Kaichiro
    Department of Cardiovascular Research, Research Institute of Environmental Medicine, Nagoya University

Search this article

Description

<p>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.</p><p>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.</p><p>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.</p>

Journal

Citations (1)*help

See more

References(42)*help

See more

Related Projects

See more

Keywords

Details 詳細情報について

Report a problem

Back to top