E-selectin blockade decreases adventitial inflammation and attenuates intimal hyperplasia in rat carotid arteries after balloon injury

E-selectin blockade decreases adventitial inflammation and attenuates intimal hyperplasia in rat carotid arteries after balloon injury
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DOI:
10.1161/01.atv.0000145942.31404.20
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发表时间:
2004-11-01
影响因子:
8.7
通讯作者:
Isobe, M
Isobe, M
中科院分区:
医学1区
文献类型:
--
作者:
Gotoh, R;Suzuki, J;Isobe, M

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目的-炎症是血管损伤后的最初修复过程之一。E-选择素促进白细胞粘附于炎症部位的血管内皮。由于E-选择素在这个过程中的作用还没有完全了解,我们研究了E-选择素在血管损伤的作用与流动室模型和大鼠模型的颈动脉injure.Methods和结果-我们建立了大鼠主动脉内皮细胞(RAEC)培养系统从成年雄性大鼠的腹主动脉。当大鼠骨髓单核细胞悬浮在流动室,滚动和粘附脂多糖(LPS)刺激的RAECs观察。加入抗E-选择素单克隆抗体(mAb)后,细胞滚动和粘附明显减少。然后,我们诱导大鼠左颈动脉球囊损伤。损伤后7天,外膜小血管内皮细胞E-选择素表达增强。用抗E-选择素单克隆抗体腹腔注射球囊损伤大鼠8天。在损伤后第7天,通过抗E-选择素mAb治疗外膜处的炎性细胞浸润减少。这种减少与用mAb处理的大鼠中内膜增生的减弱有关。结论-这些数据表明E-选择素通过白细胞粘附调节外膜炎症,并促进球囊损伤后内膜增生的过程。
Objective - Inflammation is one of the initial repair processes after vascular injury. E-selectin facilitates adherence of leukocytes to vascular endothelium at the site of inflammation. Because the role of E-selectin in this process is not fully understood, we studied the role of E-selectin in vascular injury with a flow chamber model and a rat model of carotid artery injury.Methods and Results - We established a rat aortic endothelial cell (RAEC) culture system from the aortas of adult male rats. When rat myelomonocytes were suspended in a flow chamber, rolling and adhesion to lipopolysaccharide (LPS)-stimulated RAECs were observed. Cell rolling and adhesion were greatly reduced by addition of anti - E-selectin monoclonal antibody (mAb). We then induced balloon injury in the left carotid arteries of rats. E-selectin expression was enhanced in endothelial cells at adventitial small vessels 7 days after injury. Rats with balloon injury were injected intraperitoneally with anti-E-selectin mAb for 8 days. Inflammatory cell infiltration was reduced by anti-E-selectin mAb treatment at the adventitia at 7 days after injury. This reduction was associated with attenuation of intimal hyperplasia in the rats treated with the mAb.Conclusions - These data suggest that E-selectin regulates adventitial inflammation through leukocyte adhesion and contributes to the process of intimal hyperplasia after balloon injury.