Single injection of P-selectin or P-selectin glycoprotein ligand-1 monoclonal antibody blocks neointima formation after arterial injury in apolipoprotein E-deficient mice
Single injection of P-selectin or P-selectin glycoprotein ligand-1 monoclonal antibody blocks neointima formation after arterial injury in apolipoprotein E-deficient mice
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DOI：
10.1161/01.cir.0000065604.56839.18
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发表时间：
2003-05-06
期刊：
影响因子：
37.8
通讯作者：
Sarembock, IJ
中科院分区：
文献类型：
--
作者：
Phillips, JW;Barringhaus, KG;Sarembock, IJ
背景-新出现的数据表明，通过控制白细胞的粘附，p -选择素可能在限制血管损伤反应中起重要作用。方法和结果-我们验证了一种假设，即抗p -选择素单克隆抗体（mAb）或抗p -选择素糖蛋白配体-1 （PSGL-1）单抗对p -选择素的短暂抑制可以减少动脉粥样硬化易发载脂蛋白E-/-小鼠颈动脉剥脱损伤中新内膜的形成。损伤当天单次注射100或200马克杯P-选择素单抗RB 40.34, 28天新生内膜形成显著减少50%或80%，单次注射100马克杯PSGL-1单抗4RA10，新生内膜形成显著减少55% （P小于或等于0.005）。此外，新生内膜巨噬细胞含量显著降低。结论：这些发现表明，在载脂蛋白E-/-小鼠颈动脉剥脱损伤后，动脉损伤时短暂的p -选择素或PSGL-1阻断显著地以剂量依赖的方式限制斑块巨噬细胞含量和新内膜形成。
Background - Emerging data suggest that P-selectin, by controlling adhesion of white blood cells, may be important in limiting the response to vascular injury.Methods and Results - We tested the hypothesis that transient inhibition of P-selectin with either anti - P-selectin monoclonal antibody (mAb) or anti - P-selectin glycoprotein ligand-1 ( PSGL-1) mAb would reduce neointima formation in the setting of carotid denudation injury in atherosclerosis-prone apolipoprotein E-/- mice. Neointima formation at 28 days was reduced significantly, by 50% or 80%, by a single injection on the day of injury of 100 or 200 mug P-selectin mAb RB 40.34 and by 55% by a single injection of 100 mug PSGL-1 mAb 4RA10 ( P less than or equal to 0.005). In addition, there was a significant reduction in neointimal macrophage content.Conclusions - These findings demonstrate that transient P-selectin or PSGL-1 blockade at the time of arterial injury significantly limits plaque macrophage content and neointima formation in a dose-dependent manner after carotid denudation injury in apolipoprotein E-/- mice.