Hic-5 deficiency enhances mechanosensitive apoptosis and modulates vascular remodeling
Hic-5 deficiency enhances mechanosensitive apoptosis and modulates vascular remodeling
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DOI：
10.1016/j.yjmcc.2010.09.024
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发表时间：
2011-01-01
影响因子：
5
通讯作者：
Nose, Kiyoshi
中科院分区：
文献类型：
--
作者：
Kim-Kaneyama, Joo-ri;Takeda, Naoki;Nose, Kiyoshi
与血流相关的力量不仅对血管发育至关重要，而且对血管病理的调节也是至关重要的。虽然已经有许多研究描述了对机械刺激的反应，但将生物反应与机械力联系起来的分子机制仍不清楚。HIC-5(过氧化氢诱导的克隆-5)是一种粘着斑适配器蛋白，被认为是一种机械信号转导的候选介体。在本研究中，我们通过定向突变产生了Hic-5缺陷小鼠。缺乏Hic-5的小鼠可以存活和生育，并且没有表现出明显的组织学异常，包括血管形成。然而，Hic-5基因缺陷小鼠股动脉钢丝损伤后，由于血管壁细胞凋亡增加，动脉中层组织学恢复延迟，而新生内膜形成增加。体外培养的Hic-5基因缺陷小鼠血管平滑肌细胞(VSMC)经牵张诱导的细胞凋亡增强。机械应力还引起细胞内纽蛋白分布的改变，从局部粘连到整个细胞质。免疫电子显微镜观察发现，在Hic-5基因缺陷小鼠，纽蛋白主要分布在胞核和胞浆中，而在野生型小鼠中，纽蛋白主要分布在亚质膜区。我们的研究结果表明，Hic-5可能在机械敏感性血管重塑中发挥关键调节作用。(C)2010爱思唯尔有限公司。保留所有权利。
Forces associated with blood flow are crucial not only for blood vessel development but also for regulation of vascular pathology. Although there have been many studies characterizing the responses to mechanical stimuli, molecular mechanisms linking biological responses to mechanical forces remain unclear. Hic-5 (hydrogen peroxide-inducible clone-5) is a focal adhesion adaptor protein proposed as a candidate for a mediator of mechanotransduction. In the present study, we generated Hic-5-deficient mice by targeted mutation. Mice lacking Hic-5 are viable and fertile, and show no obvious histological abnormalities including vasculature. However, after wire injury of the femoral artery in Hic-5 deficient mice, histological recovery of arterial media was delayed due to enhanced apoptosis of vascular wall cells, whereas neointima formation was enhanced. Stretch-induced apoptosis was enhanced in cultured vascular smooth muscle cells (vascular SMCs) from Hic-5 deficient mice. Mechanical stress also induced the alteration of intracellular distribution of vinculin from focal adhesions to the whole cytoplasm in SMCs. Immunoelectron microscopic study of vascular SMCs from a wire-injured artery demonstrated that vinculin was dispersed in the nucleus and the cytoplasm in Hic-5-deficient mice whereas vinculin was localized mainly in the sub-plasma membrane region in wild type mice. Our findings indicate that Hic-5 may serve as a key regulator in mechanosensitive vascular remodeling. (C) 2010 Elsevier Ltd. All rights reserved.