Fluorescence microscopic observation of the dynamics of early lesion formation after vascular injury in LDLR-/- mice in vivo
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KeyWord:In vivo fluorescence; low-density lipoprotein receptor knockout mice; vascular injury
高岱岳 黑龙江中医药大学中医药研究院,哈尔滨
高蒙蒙 中国医学科学院北京协和医学院药用植物研究所,北京
秦蒙 中国医学科学院北京协和医学院药用植物研究所,北京
王丽丽 中国医学科学院北京协和医学院药用植物研究所,北京
吕新勇 江苏康缘药业股份有限公司,江苏省连云港
王振中 江苏康缘药业股份有限公司,江苏省连云港
萧伟 江苏康缘药业股份有限公司,江苏省连云港
刘树民 黑龙江中医药大学中医药研究院,哈尔滨
许扬 中国医学科学院北京协和医学院药用植物研究所,北京
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      ObjectiveTo study the early dynamics of lesion formation after vascular injury in LDLR-/- mice by in vivo fluorescence microscopy. MethodsOne hundred and twelve male LDLR-/- mice (18-22 weeks of age) were randomly divided into 14 groups (8 mice in each group). The mice were subjected to bone marrow cell transplantation from GFP+/LDLR-/- mice. After 4 weeks, a polyethylene cuff was implanted around the right femoral artery to induce vascular injury. The lesion formation was observed on the injured femoral artery from 1 to 14 days after vascular injury.ResultsAt the 1st day after cuff placement, a markedly large number of GFP positive cells were clearly observed in high-speed blood flow. At the 3rd day after the vascular injury, GFP positive cells accumulated in the inner vascular wall and formed punctate lesions. At the 6th day after the vascular injury, GFP positive cells in the inner vascular wall formed irregular flakes, and a small amount of the adventitia tissue proliferated, corresponding to the inner lesion area. At the 9th day after the vascular injury, the adventitia tissue was obviously proliferated and a large number of GFP positive cells embeded. The vasa vasorum were clearly seen running in the adventitial layer. At the 14th day after the vascular injury, the adventitia tissue proliferated considerably with largely GFP positive cells and could not be observed in the lesion through adventitia. After stripping the outer tissue of vessel wall, the fluorescent lesion formed by GFP positive cells was clearly lining in the intima area.ConclusionsThe results of our study demonstrate that the vascular remodeling lesion in the early stage in LDLR-/- mice has a trend of “inside out”. The dynamics of lesions has a close correlation with bone marrow-derived cells that circulating in the blood flow. There is distinct influence of the vascular lesions on extravascular fibrosis. 
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