Monocyte chemotactic protein-1 expression is associated with the development of vein graft intimal hyperplasia
Monocyte chemotactic protein-1 expression is associated with the development of vein graft intimal hyperplasia
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DOI：
10.1161/01.atv.17.8.1614
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发表时间：
1997-08-01
影响因子：
8.7
通讯作者：
Hullett, DA
中科院分区：
文献类型：
--
作者：
Stark, VK;Hoch, JR;Hullett, DA
免疫活性细胞在移植静脉中的渗透伴随着内膜增生(IH)的发展，常常导致闭塞性狭窄和移植失败。以前的工作已经证明单核细胞和巨噬细胞在静脉筏中的存在时间较长。吸引这些巨噬细胞的a刺激因素仍未确定。单核细胞趋化蛋白-1(MCP-1)是一种高效、特异的单核/巨噬细胞趋化因子，由移植静脉中的平滑肌细胞、内皮细胞、成纤维细胞和白细胞分泌。本研究采用逆转录-聚合酶链式反应和免疫组织化学方法检测了大鼠移植静脉MCP-1基因表达的时间分布。在移植后的不同时间点，显微外科手术放置上腹部静脉-股动脉搭桥移植物，并采集移植物。组织学分析证实了IH的持续发展。用聚合酶链式反应和放射自显影测定MCP-1的相对水平。结果表明，移植后4小时，MCP-1基因表达水平增加28倍，1周后增加117倍。在这段时间之后，MCP-1mRNA水平下降；尽管如此，即使在移植后8周，消息水平仍然高于基线的7倍。各时间点均检测到免疫反应阳性的MCP-1蛋白和ED1+巨噬细胞，免疫染色程度与MCP-1mRNA水平呈正相关。我们的结果支持这样的假设，即静脉移植物中MCP-1基因表达上调导致单核细胞和组织巨噬细胞向静脉壁募集。单核/巨噬细胞浸润与IH的相关性提示这些细胞在IH的发生发展中起着关键作用。
Infiltration of immunologically active cells into vein grafts is concomitant with the development of intimal hyperplasia (IH) and often leads to obliterative stenosis and graft failure. Previous work has demonstrated the prolonged presence of monocytes and macrophages in vein rafts. The a stimuli attracting these macrophages remain unidentified. Monocyte chemotactic protein-1 (MCP-1), a potent and specific chemokine for monocytes/macrophages, is secreted by smooth muscle cells, endothelial cells, fibroblasts, and leukocytes, all of which are present in grafted veins. In this study, we examined the temporal profile of MCP-1 gene expression in rat vein grafts by using reverse transcription-polymerase chain reaction (PCR) and immunohistochemistry. Epigastric vein-to-femoral artery bypass grafts were microsurgically placed and harvested at various time points after grafting. Histological analysis confirmed the consistent development of IH. PCR was performed and relative levels of MCP-1 quantified by autoradiography. Our results show that MCP-1 mRNA levels in creased 28-fold by 4 hours after grafting and up to 117-fold by 1 week. After this time MCP-1 mRNA levels decreased; nonetheless, even at 8 weeks after grafting, message levels remained elevated 7-fold above baseline. Immunoreactive MCP-1 protein and ED1+ macrophages were detected at all time points; the degree of immunostaining correlated with MCP-1 mRNA levels. Our results support the hypothesis that upregulation of MCP-1 gene expression in vein grafts results in the recruitment of monocytes and tissue macrophages to the vein wall. which leads to M. The correlation between monocyte/macrophage infiltration and IH suggests a critical role for these cells in IH development.