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

• Published in: The Journal of clinical investigation Vol. 105; no. 4; pp. 489 - 495
• Main Authors: Horiba, M, Kadomatsu, K, Nakamura, E, Muramatsu, H, Ikematsu, S, Sakuma, S, Hayashi, K, Yuzawa, Y, Matsuo, S, Kuzuya, M, Kaname, T, Hirai, M, Saito, H, Muramatsu, T
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 15.02.2000
• Subjects: Angioplasty, Balloon - adverse effects; Animals; Arterial Occlusive Diseases - therapy; Arteriosclerosis - therapy; Arteritis - therapy; Carotid Stenosis - therapy; Carrier Proteins - genetics; Cell Movement; Cells, Cultured; Cytokines; Gene Expression; Macrophages - cytology; Male; Mice; Mice, Mutant Strains; Muscle, Smooth, Vascular; Nerve Growth Factors - genetics; Rats; Rats, Sprague-Dawley; Tunica Intima - pathology
• ISSN: 0021-9738
• DOI: 10.1172/jci7208

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.