Schepers A, Eefting D, Bonta P I, Grimbergen J M, de Vries M R, van Weel V, de Vries C J, Egashira K, van Bockel J H, Quax P H A
Gaubius Laboratory, TNO-Quality of Life, Leiden, The Netherlands.
Arterioscler Thromb Vasc Biol. 2006 Sep;26(9):2063-9. doi: 10.1161/01.ATV.0000235694.69719.e2. Epub 2006 Jul 6.
Because late vein graft failure is caused by intimal hyperplasia (IH) and accelerated atherosclerosis, and these processes are thought to be inflammation driven, influx of monocytes is one of the first phenomena seen in IH, we would like to provide direct evidence for a role of the MCP-1 pathway in the development of vein graft disease.
MCP-1 expression is demonstrated in various stages of vein graft disease in a murine model in which venous interpositions are placed in the carotid arteries of hypercholesterolemic ApoE3Leiden mice and in cultured human saphenous vein (HSV) segments in which IH occurs. The functional involvement of MCP-1 in vein graft remodeling is demonstrated by blocking the MCP-1 receptor CCR-2 using 7ND-MCP-1. 7ND-MCP1 gene transfer resulted in 51% reduction in IH in the mouse model, when compared with controls. In HSV cultures neointima formation was inhibited by 53%. In addition, we demonstrate a direct inhibitory effect of 7ND-MCP-1 on the proliferation of smooth muscle cell (SMC) in HSV cultures and in SMC cell cultures.
These data, for the first time, prove that MCP-1 has a pivotal role in vein graft thickening due to intimal hyperplasia and accelerated atherosclerosis.
由于晚期静脉移植物失败是由内膜增生（IH）和加速动脉粥样硬化引起的，并且这些过程被认为是由炎症驱动的，单核细胞流入是在IH中最早出现的现象之一，我们希望为MCP-1途径在静脉移植物疾病发展中的作用提供直接证据。
在高胆固醇血症ApoE3 Leiden小鼠颈动脉中植入静脉间置物的小鼠模型以及发生IH的培养人隐静脉（HSV）段的静脉移植物疾病的各个阶段中均证实了MCP-1的表达。通过使用7ND-MCP-1阻断MCP-1受体CCR-2，证明了MCP-1在静脉移植物重塑中的功能参与。与对照组相比，7ND-MCP1基因转移使小鼠模型中的IH减少了51%。在HSV培养物中，新生内膜形成受到53%的抑制。此外，我们证明了7ND-MCP-1对HSV培养物和平滑肌细胞（SMC）培养物中平滑肌细胞（SMC）增殖具有直接抑制作用。
这些数据首次证明，MCP-1在因内膜增生和加速动脉粥样硬化导致的静脉移植物增厚中起关键作用。
