Lack of Neutrophil-Derived CRAMP Reduces Atherosclerosis in Mice
Lack of Neutrophil-Derived CRAMP Reduces Atherosclerosis in Mice
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DOI：
10.1161/circresaha.112.265868
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发表时间：
2012-04-13
影响因子：
20.1
通讯作者：
Soehnlein, Oliver
中科院分区：
文献类型：
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作者：
Doering, Yvonne;Drechsler, Maik;Soehnlein, Oliver
依据：据报道中性粒细胞可促进早期动脉粥样硬化病变的形成。目的：研究嗜中性粒细胞颗粒蛋白cathelicidin（CRAMP）在小鼠动脉粥样硬化中的作用，方法和结果：与ApoE（-/-）小鼠相比，Cramp（-/-）ApoE（-/-）小鼠的病变体积减小，巨噬细胞数量减少。在动脉粥样硬化性动脉瘤中，我们可以在中性粒细胞中特异性检测到CRAMP，但在单核细胞或巨噬细胞中不能检测到。通过使用活体显微镜，发现CRAMP由活化的中性粒细胞沉积在大动脉的发炎内皮上。在这个位置cathelicidins促进经典的单核细胞和中性粒细胞的粘附，但不是非经典的单核细胞在甲酰肽受体依赖的martens.Conclusions：Cathelicidins促进动脉粥样硬化通过增强炎症单核细胞的招聘。(Circ Res. 2012;110：1052-1056）。
Rationale: Neutrophils have been reported to contribute to early atherosclerotic lesion formation. Mechanisms of neutrophil-driven atherosclerosis remain unclear so far.Objective: Investigation of the role of the neutrophil granule protein cathelicidin (CRAMP in mouse, LL37 in human) in atherosclerosis.Methods and Results: Compared to Apoe(-/-) mice, Cramp(-/-) Apoe(-/-) mice exhibit reduced lesion sizes with lower macrophage numbers. In atherosclerotic aortas, we could detect CRAMP specifically in neutrophils, but not in monocytes or macrophages. By use of intravital microscopy, CRAMP was found to be deposited by activated neutrophils on inflamed endothelium of large arteries. In this location cathelicidins promote adhesion of classical monocytes and neutrophils, but not nonclassical monocytes in a formyl-peptide receptor-dependent manner.Conclusions: Cathelicidins promote atherosclerosis by enhancement of the recruitment of inflammatory monocytes. (Circ Res. 2012;110:1052-1056.)