Liu Peng, Patil Sarita, Rojas Mauricio, Fong Alan M, Smyth Susan S, Patel Dhavalkumar D
Department of Medicine, University of North Carolina at Chapel Hill, USA.
Arterioscler Thromb Vasc Biol. 2006 Sep;26(9):2056-62. doi: 10.1161/01.ATV.0000234947.47788.8c. Epub 2006 Jun 29.
A functional polymorphism in the chemokine receptor CX3CR1 is associated with protection from vascular diseases including coronary artery disease and internal carotid artery occlusive disease. We investigated the mechanisms by which CX3CR1 may be involved by evaluating the inflammatory response to arterial injury in CX3CR1-deficient animals.
Femoral arteries of CX3CR1-/- and wild-type (WT) mice were injured with an angioplasty guide wire. After 1, 5, 14, and 28 days, arteries were harvested and evaluated by histology, morphometry, and immunohistochemistry. Arterial injury upregulated the CX3CR1 ligand CX3CL1. In CX3CR1-/- compared with WT animals, the incidence of neointima formation was 58% lower (P=0.0017), accompanied by no difference in the area of platelet accumulation at day 1 (P=0.48) but a significant decrease in intimal monocyte infiltration at day 5 (P=0.006), vascular smooth muscle cell (VSMC) proliferation at days 5 and 14, and intimal area at day 28 (P=0.009).
In an endothelial denudation injury model, CX3CR1 deficiency protects animals from developing intimal hyperplasia as a result of decreased monocyte trafficking to the lesion. CX3CR1 deficiency decreases VSMC proliferation and intimal accumulation either directly or indirectly as a result of defective monocyte infiltration.
趋化因子受体CX3CR1的功能多态性与预防包括冠状动脉疾病和颈内动脉闭塞性疾病在内的血管疾病相关。我们通过评估CX3CR1缺陷动物对动脉损伤的炎症反应，研究了CX3CR1可能涉及的机制。
用血管成形术导丝损伤CX3CR1基因敲除小鼠和野生型（WT）小鼠的股动脉。在1、5、14和28天后，采集动脉并通过组织学、形态计量学和免疫组织化学进行评估。动脉损伤使CX3CR1配体CX3CL1上调。与WT动物相比，CX3CR1基因敲除动物的内膜形成发生率降低了58%（P=0.0017），第1天血小板聚集面积无差异（P=0.48），但第5天内膜单核细胞浸润显著减少（P=0.006），第5天和第14天血管平滑肌细胞（VSMC）增殖以及第28天内膜面积显著减少（P=0.009）。
在内皮剥脱损伤模型中，CX3CR1缺陷可保护动物免受内膜增生，这是由于单核细胞向病变部位的迁移减少所致。CX3CR1缺陷可直接或间接因单核细胞浸润缺陷而减少VSMC增殖和内膜积聚。
