Mouse model of transplant arteriosclerosis - Role of intercellular adhesion molecule-1
Mouse model of transplant arteriosclerosis - Role of intercellular adhesion molecule-1
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DOI：
10.1161/01.atv.20.2.343
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发表时间：
2000-02-01
影响因子：
8.7
通讯作者：
Xu, QB
中科院分区：
文献类型：
--
作者：
Dietrich, H;Hu, YH;Xu, QB
冠状动脉移植加速动脉硬化是心脏移植患者长期生存的主要限制。这种疾病的发病机制尚不完全清楚。在此，我们描述了小鼠动脉同种异体移植的简化模型，该模型使我们能够利用转基因、敲除或突变动物，将颈总动脉或主动脉血管端对端同种异体移植到 C57BL/6J 和 BALB/c 小鼠之间的颈动脉中。早在术后 2 周就观察到新内膜病变，并在术后 4 周和 6 周时出现进展。移植后4周，由于新内膜增生，移植动脉管腔明显变窄。利用该模型，我们研究了细胞间粘附分子 1 (ICAM-1) 在 ICAM-1 缺陷小鼠移植动脉硬化发展中的作用。与野生型对照相比，ICAM-1 -/- C57BL/6J 至 BALB/c 小鼠的动脉移植物的新内膜病变减少了 60%，通过 enface 免疫荧光检测发现，ICAM-1 -/- 动脉移植物表面粘附的 MAC-1 (CD11b/18) 阳性细胞明显减少，并且这些阳性细胞在野生型小鼠动脉移植物的内膜病变中更为丰富。此外，术后4周新生内膜病变的主要细胞成分被发现是α-肌动蛋白阳性平滑肌细胞，其在ICAM-1 -/- 动脉移植物的病变中显着减少。因此，该模型已被证明有助于理解移植动脉硬化的机制。我们的研究结果表明，ICAM-1 通过介导白细胞粘附和浸润血管壁，在同种异体移植物动脉硬化的发展中发挥关键作用。
Transplant-accelerated arteriosclerosis in coronary arteries is the major limitation to long-term survival of patients with heart transplantation. The pathogenesis of this disease is not fully understood. Herein, we describe a simplified model of artery allografts in the mouse that allows us to take advantage of transgenic, knockout, or mutant animals, Common carotid arteries or aortic vessels were end-to-end allografted into carotid arteries between C57BL/6J and BALB/c mice. Neointimal lesions were observed as early as 2 weeks after surgery and had progressed at 4 and 6 weeks postoperatively. The lumen of grafted arteries was significantly narrowed due to neointima hyperplasia 4 weeks after transplantation. Using this model, we studied the role of intercellular adhesion molecule-1 (ICAM-1) in the development of transplant arteriosclerosis in ICAM-1-deficient mice. Neointimal lesions of artery grafts from ICAM-1 -/- C57BL/6J to BALB/c mice were reduced up to 60% compared with wild-type controls, MAC-1 (CD11b/18)-positive cells adhering to the surface of ICAM-1 -/- artery grafts were significantly less as identified by en face immunofluorescence, and these positive cells were more abundant in intimal lesions of artery grafts in wild-type mice. Furthermore, the major cell component of neointimal lesions 4 weeks after surgery was found to be alpha-actin-positive smooth muscle cells, which were significantly reduced in lesions of ICAM-1 -/- artery grafts. Thus, this model has been proven to be useful for understanding the mechanism of transplant arteriosclerosis. Our findings demonstrate that ICAM-1 is critical in the development of allograft arteriosclerosis via mediation of leukocyte adhesion to, and infiltration into, the vessel wall.