EFFECTS OF MIDKINE ON NEOINTIMA FORMATION IN A RESTENOSIS MODEL

Research Project

Project/Area Number	10670643
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Circulatory organs internal medicine
Research Institution	NAGOYA UNIVERSITY
Principal Investigator	HIRAKI Makoto SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 講師 (90242875)
Co-Investigator(Kenkyū-buntansha)	KADOMATSU Kenji SCHOOL OF MEDICINE, Associate Professor, 医学部, 助教授 (80204519) MURAMATSU Takashi SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (00030891)
Project Period (FY)	1998 – 1999
Project Status	Completed (Fiscal Year 1999)
Budget Amount *help	¥3,200,000 (Direct Cost: ¥3,200,000) Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000) Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywords	atherosclerosis / chemotaxis / growth substances / inflammation / knockout mice / ミッドカイン(MK) / 新生内膜増殖 / PTN
Research Abstract	Neointimal 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 mic 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 due to its ability to mediate leukocyte recruitment.