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颈动脉或股动脉损伤后CX3CR1/平滑肌样细胞的内皮覆盖差异、对损伤的反应及新生内膜整合

Differential endothelial coverage, response to injury and neointimal integration of CX3CR1/smooth muscle-like cells after carotid or femoral arterial injury.

作者信息

Martin Kenneth, Kumar Arun H S, Klinkert Kerstin, Caplice Noel M

机构信息

Biosciences Institute, University College Cork, Centre for Research in Vascular Biology, Cork, Ireland.

出版信息

J Vasc Res. 2013;50(3):200-9. doi: 10.1159/000350532. Epub 2013 May 3.

DOI:10.1159/000350532
PMID:23653073
Abstract

BACKGROUND

Previously, we established the importance of the CX3CL1/CX3CR1 axis in the promotion of myeloid cell differentiation into neointimal smooth muscle-like cells (SMLC).

METHODS

In this study, acute (24 h) endothelial coverage and CX3CL1 expression as well as chronic (2 weeks) vascular remodeling was examined with respect to whether myeloid CX3CR1(+) SMLC number in the neointima differed between carotid and femoral artery wire injury.

RESULTS AND CONCLUSION

Twenty-four hours after injury, CX3CL1 expression was significantly elevated in injured carotid compared to femoral arteries. In mice with CX3CR1 promoter-driven expression of green fluorescent protein, neointima formation was significantly greater (p < 0.05) 2 weeks after injury in femoral versus carotid arteries as determined by the intima/media ratio. Although the percentage of F4/80/CX3CR1(+) cell integration was similar in both models, the carotid lesion had greater proportions of cells coexpressing CX3CR1 and both α-smooth muscle actin and calponin (p < 0.05). Wire injury of carotid arteries was associated with greater CX3CL1 expression in the acute phase followed by greater CX3CR1 coexpressing SMLC content in later lesions as well as less neointima formation than in femoral arteries. This may, in part, explain the variability in lesion composition after carotid versus femoral wire injury.

摘要

背景

此前,我们已证实CX3CL1/CX3CR1轴在促进髓样细胞分化为新生内膜平滑肌样细胞(SMLC)中的重要性。

方法

在本研究中,针对颈动脉和股动脉钢丝损伤后新生内膜中髓样CX3CR1(+) SMLC数量是否存在差异,检测了急性(24小时)内皮覆盖情况和CX3CL1表达以及慢性(2周)血管重塑情况。

结果与结论

损伤后24小时,与股动脉相比,损伤的颈动脉中CX3CL1表达显著升高。在CX3CR1启动子驱动绿色荧光蛋白表达的小鼠中,损伤后2周,通过内膜/中膜比值测定,股动脉的新生内膜形成明显大于颈动脉(p < 0.05)。尽管在两种模型中F4/80/CX3CR1(+)细胞整合的百分比相似,但颈动脉病变中同时表达CX3CR1以及α平滑肌肌动蛋白和钙调蛋白的细胞比例更高(p < 0.05)。颈动脉钢丝损伤在急性期与更高的CX3CL1表达相关,随后在后期病变中与更高的共表达CX3CR1的SMLC含量相关,并且与股动脉相比新生内膜形成更少。这可能部分解释了颈动脉与股动脉钢丝损伤后病变组成的差异。

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