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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Monocyte accumulation in mouse atherogenesis is progressive and proportional to extent of disease
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Monocyte accumulation in mouse atherogenesis is progressive and proportional to extent of disease

机译：小鼠动脉粥样硬化中的单核细胞积累是渐进的，并且与疾病程度成正比

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Monocytes participate importantly in the pathogenesis of atherosclerosis, but their spatial and temporal recruitment from circulation remains uncertain. This study tests the hypothesis that monocyte accumulation in atheroma correlates with the extent of disease by using a sensitive and simple quantitative assay that allows tracking of highly enriched populations of blood monocytes. A two-step isolation method yielded viable and functionally intact highly enriched peripheral blood monocyte populations (> 90%). Recipient mice received syngeneic monocytes labeled in two ways: by transgenically expressing EGFP or with a radioactive tracer [In-111]oxine. After 5 days, more labeled cells accumulated in the aorta, principally the aortic root and ascending aorta, of 10-wk-old ApoE(-/-) compared with 10-wk-old C57BL/6 mice (223 +/- 3 vs. 87 +/- 22 cells per aorta). Considerably more monocytes accumulated in 20-wk-old ApoE(-/-) mice on either chow (314 +/- 41 cells) or high-cholesterol diet (395 +/- 53 cells). Fifty-week-old ApoE(-/-) mice accumulated even more monocytes in the aortic root, ascending aorta, and thoracic aorta after both chow (503 +/- 67 cells) or high-cholesterol diet (648 81 cells). Labeled monocyte content in the aorta consistently correlated with lesion surface area. These data indicate that monocytes accumulate continuously during atheroma formation, accumulation increases in proportion to lesion size, and recruitment is augmented with hypercholesterolemia. These results provide insights into mechanisms of atherogenesis and have implications for the duration of therapies directed at leukocyte recruitment.
机译：单核细胞重要参与动脉粥样硬化的发病机理，但其从循环中的时空募集仍然不确定。这项研究通过使用一种敏感而简单的定量分析方法来检测动脉粥样硬化中单核细胞积累与疾病程度有关的假说，该定量分析方法可以追踪高度富集的血液单核细胞群体。两步分离方法可产生可行且功能完整的高度富集的外周血单核细胞群（> 90％）。收件人小鼠接受以两种方式标记的同基因单核细胞：通过转基因表达EGFP或使用放射性示踪剂[In-111] oxine。 5天后，与10周龄的C57BL / 6小鼠相比，10周龄的ApoE（-/-）在主动脉中积累的标记细胞更多，主要是主动脉根和升主动脉（223 +/- 3 vs每个主动脉87 +/- 22个细胞）。在20周大的ApoE（-/-）小鼠中，通过食物（314 +/- 41个细胞）或高胆固醇饮食（395 +/- 53个细胞）积累了相当多的单核细胞。五十周龄的ApoE（-/-）小鼠在经过食物（503 +/- 67个细胞）或高胆固醇饮食（648 81个细胞）后，在主动脉根，升主动脉和胸主动脉中积累了更多的单核细胞。主动脉中标记的单核细胞含量始终与病变表面积相关。这些数据表明单核细胞在动脉粥样硬化形成过程中连续积累，积累与病变大小成正比，高胆固醇血症会增加募集。这些结果提供了对动脉粥样硬化形成机理的见解，并且对针对白细胞募集的治疗持续时间有影响。

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