Neointima formation in a restenosis model is suppressed in midkine-deficient mice.
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.
Horiba
M
M
Department of Biochemistry, Nagoya University School of Medicine, Nagoya 466-8550, Japan. tmurama@tsuru.med.nagoya-u.ac.jp
Kadomatsu
K
K
Nakamura
E
E
Muramatsu
H
H
Ikematsu
S
S
Sakuma
S
S
Hayashi
K
K
Yuzawa
Y
Y
Matsuo
S
S
Kuzuya
M
M
Kaname
T
T
Hirai
M
M
Saito
H
H
Muramatsu
T
T
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000628:therapy*; D001161:Arteriosclerosis / Q000628:therapy; D001167:Arteritis / Q000628:therapy; D016893:Carotid Stenosis / Q000628:therapy; D002352:Carrier Proteins / Q000235:genetics*; D002465:Cell Movement; D002478:Cells, Cultured; D016207:Cytokines; D015870:Gene Expression; D008264:Macrophages / Q000166:cytology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D000078792:Midkine; D009131:Muscle, Smooth, Vascular; D009414:Nerve Growth Factors / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017539:Tunica Intima / Q000473:pathology*
D002352:Carrier Proteins; D016207:Cytokines; D009414:Nerve Growth Factors; D000078792:Midkine