Early growth response protein 1 promotes restenosis by upregulating intercellular adhesion molecule-1 in vein graft.

Early growth response protein 1 promotes restenosis by upregulating intercellular adhesion molecule-1 in vein graft.
复制标题

早期生长反应蛋白 1 通过上调静脉移植物中的细胞间粘附分子 1 促进再狭窄。

DOI:
10.1155/2013/432409
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发表时间:
2013
影响因子:
--
通讯作者:
Du J
Du J
中科院分区:
生物学2区
文献类型:
--
作者:
Zhang K;Cao J;Dong R;Du J

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目标.目的探讨Egr-1与移植静脉再狭窄的关系及相关机制。方法.在Egr-1敲除(KO)和野生型(WT)小鼠中建立小鼠静脉移植物模型。取移植静脉进行病理学检查和免疫组化分析。内皮细胞(EC)的刺激,通过使用一个计算机控制的循环应力单元。BrdU染色检测ECs增殖活性,PCR检测Egr-1和ICAM-1 mRNA表达。Western-blot检测Egr-1和细胞间粘附分子-1(ICAM-1)蛋白的表达。结果Egr-1基因敲除小鼠移植静脉的管腔比野生型小鼠宽。Egr-1基因敲除可抑制机械牵张刺激后的ECs增殖(P < 0.05)。机械牵张刺激后,移植静脉和内皮细胞Egr-1和ICAM-1的mRNA和蛋白表达均增加(P < 0.05)。Egr-1基因敲除小鼠内皮细胞ICAM-1表达明显降低(P < 0.05)。结论. Egr-1可能通过上调ICAM-1的表达而促进内皮细胞增殖,导致移植静脉再狭窄。作为静脉移植物再狭窄的关键因素,它可能成为预防CABG术后再狭窄的靶点。
Objectives. To verify the relationship between Egr-1 and vein graft restenosis and investigate the related mechanisms. Methods. Mouse vein graft models were established in Egr-1 knockout (KO) and wild-type (WT) mice. The vein grafts in the mice were taken for pathological examination and immunohistochemical analysis. The endothelial cells (ECs) were stimulated by using a computer-controlled cyclic stress unit. BrdU staining and PCR were used to detect ECs proliferation activity and Egr-1 and ICAM-1 mRNA expression, respectively. Western-blot analysis was also used to detect expression of Egr-1 and intercellular adhesion molecule-1 (ICAM-1) proteins. Results. The lumens of vein grafts in Egr-1 KO mice were wider than in WT mice. ECs proliferation after mechanical stretch stimulation was suppressed by Egr-1 knockout (P < 0.05). Both in vein grafts and ECs from WT mice after mechanical stretch stimulation, mRNA expression and protein of Egr-1 and ICAM-1 showed increases (P < 0.05). However, ICAM-1 expression was significantly suppressed in ECs from Egr-1 knockout mice (P < 0.05). Conclusions. Egr-1 may promote ECs proliferation and result in vein graft restenosis by upregulating the expression of ICAM-1. As a key factor of vein graft restenosis, it could be a target for the prevention of restenosis after CABG surgery.
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