Endothelial cell-selective adhesion molecule modulates atherosclerosis through plaque angiogenesis and monocyte-endothelial interaction
Endothelial cell-selective adhesion molecule modulates atherosclerosis through plaque angiogenesis and monocyte-endothelial interaction
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DOI：
10.1016/j.mvr.2010.04.005
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发表时间：
2010-09-01
影响因子：
3.1
通讯作者：
Hirata, Ken-ichi
中科院分区：
文献类型：
--
作者：
Inoue, Michihiko;Ishida, Tatsuro;Hirata, Ken-ichi
内皮细胞选择性粘附分子（Endothelial - cell-selective adhesion molecule， ESAM）是免疫球蛋白超家族的新成员，在血管内皮细胞中表达。先前的研究表明，ESAM调节血管生成、内皮通透性和白细胞转运。然而，关于ESAM在动脉粥样硬化中的作用知之甚少。在这项研究中，我们评估了ESAM失活对小鼠动脉粥样硬化的影响。将ESAM-/-小鼠与apoE-/-小鼠杂交产生双敲除小鼠，并对apoE-/-和ESAM-/- apoE-/-小鼠主动脉病变大小进行组织学比较。虽然ESAM-/- apoE-/-小鼠血浆胆固醇水平较高，但病变大小明显小于apoE-/-小鼠。ESAM-/- apoE-/-小鼠血管壁血管血管和巨噬细胞数量减少。体外粘附实验显示，不表达ESAM的THP-1细胞与ESAM包被的培养板结合，表明ESAM可能与单核细胞上的嗜异性配体相互作用。此外，内皮单层siRNA下调ESAM可减少THP-1细胞的跨内皮迁移。综上所述，ESAM失活可以通过抑制斑块新生血管和巨噬细胞向动脉粥样硬化的浸润来降低动脉粥样硬化的易感性。(C) 2010爱思唯尔公司版权所有。
Endothelial cell-selective adhesion molecule (ESAM) is a new member of the immunoglobulin superfamily, which is expressed in vascular endothelial cells. Previous studies have demonstrated that ESAM regulates angiogenesis, endothelial permeability, and leukocyte transmigration. However, little is known concerning the role of ESAM in atherosclerosis. In this study, we assessed the effects of ESAM inactivation on atherosclerosis in mice. ESAM-/- mice were bred with apoE-/- mice to generate double knockout mice, and the aortic lesion size of apoE-/- and ESAM-/- apoE-/- mice was compared histologically. Although plasma cholesterol levels were higher in ESAM-/- apoE-/- mice, the lesion size was markedly smaller than in apoE-/- mice. ESAM-/- apoE-/- mice exhibited a decrease in the number of vasa vasorum and macrophages in the vessel wall. In vitro adhesion assays showed that THP-1 cells, which did not express ESAM, bound to the ESAM-coated culture plates, suggesting that ESAM may interact with heterophilic ligand(s) on monocytes. Moreover, downregulation of ESAM by siRNA in the endothelial monolayer diminished transendothelial migration of THP-1 cells. In conclusion, ESAM inactivation can reduce susceptibility to atherosclerosis by inhibiting plaque neovascularization and macrophage infiltration into the atheroma. (C) 2010 Elsevier Inc. All rights reserved.