Neointima formation in a restenosis model is suppressed in midkine-deficient mice
Neointima formation in a restenosis model is suppressed in midkine-deficient mice
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DOI：
10.1172/jci7208
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发表时间：
2000-02-01
影响因子：
15.9
通讯作者：
Muramatsu, T
中科院分区：
文献类型：
--
作者：
Horiba, M;Kadomatsu, K;Muramatsu, T
新内膜形成是球囊血管成形术后动脉粥样硬化和再狭窄的共同特征。为了找到抑制新内膜形成的新靶点，我们研究了中期因子 (MK)（一种具有神经营养和趋化活性的肝素结合生长因子）在新内膜形成中的可能作用。大鼠颈动脉腔内球囊损伤引起的新内膜形成过程中 MK 表达增加。在 MK 缺陷小鼠中，再狭窄模型中的新内膜形成受到强烈抑制。对 MK 缺陷小鼠连续施用 MK 蛋白可恢复新内膜形成。在 MK 缺陷小鼠中，受伤后向血管壁募集的白细胞明显减少。可溶性 MK 以及与培养基结合的 MK 可诱导巨噬细胞体外迁移。这些结果表明 MK 在新内膜形成中起关键作用，至少部分归因于其介导白细胞募集的能力。
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.