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
J Clin Invest. 2000;
105(4):489
doi:10.1172/JCI7208
Abstract |
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eointima 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.
