Neointima formation in a restenosis model is suppressed in midkine- deficient mice

Mitsuru Horiba, Kenji Kadomatsu, Eishin Nakamura, Hisako Muramatsu, Shinya Ikematsu, Sadatoshi Sakuma, Kenji Hayashi, Yukio Yuzawa, Seiichi Matsuo, Masafumi Kuzuya, Tadashi Kaname, Makoto Hirai, Hidehiko Saito, Takashi Muramatsu

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171 Citations (Scopus)


Neointima formation is a common feature of atherosclerosis and restenosis after balloon angioplasty. To find a new target to suppress neointima formation, we investigated the possible role of midkine (MK), a heparin-binding growth factor with neurotrophic and chemotactic activities, in neointima formation. MK expression increased during neointima formation caused by intraluminal balloon injury of the rat carotid artery. Neointima formation in a restenosis model was strongly suppressed in MK-deficient mice. Continuous administration of MK protein to MK-deficient mice restored neointima formation. Leukocyte recruitment to the vascular walls after injury was markedly decreased in MK-deficient mice. Soluble MK as well as that bound to the substratum induced migration of macrophages in vitro. These results indicate that MK plays a critical role in neointima formation at least in part owing to its ability to mediate leukocyte recruitment.

Original languageEnglish
Pages (from-to)489-495
Number of pages7
JournalJournal of Clinical Investigation
Issue number4
Publication statusPublished - 02-2000
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Medicine(all)


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