CD36 in the periphery and brain synergizes in stroke injury in hyperlipidemia.

CD36 in the periphery and brain synergizes in stroke injury in hyperlipidemia.
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DOI:
10.1002/ana.23569
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发表时间:
2012-06
影响因子:
11.2
通讯作者:
Cho, Sunghee
Cho, Sunghee
中科院分区:
医学1区
文献类型:
--
作者:
Kim, Eunhee;Febbraio, Maria;Bao, Yi;Tolhurst, Aaron T.;Epstein, Jeffrey M.;Cho, Sunghee

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高血压加重缺血性卒中结局,并增加缺血后脑以及外周单核细胞/巨噬细胞中的CD 36表达。通过在CD 36表达和CD 36缺陷小鼠之间交换骨髓来源的细胞,本研究调查了外周CD 36与脑CD 36对高脂血症中中风病理学的贡献。在骨髓移植后,小鼠被喂食高脂肪饮食11周,然后经历缺血性中风。在缺血后3天测定中风结果、脑CD 36、MCP-1、CCR 2的表达和血浆MCP-1水平。还测定了与从CD 36表达或CD 36缺陷小鼠获得的血清孵育的脾细胞中的CD 36和CCR 2表达。从外周浸润的免疫细胞是缺血后脑中CD 36的主要来源,并有助于卒中诱导的脑损伤。这种CD 36效应依赖于外周免疫细胞中MCP-1和CCR 2表达以及宿主脑中表达CD 36的细胞的调节。这项研究表明,在外周和脑中表达的CD 36通过在高血压条件下调节MCP-1/CCR 2趋化因子轴在缺血性脑损伤中协同作用。
Hyperlipidemia exacerbates ischemic stroke outcome and increased CD36 expression in the post-ischemic brain as well as in peripheral monocytes/macrophages. By exchanging bone marrow-derived cells between CD36-expressing and –deficient mice, this study investigates the contribution of peripheral CD36 vs brain CD36 to stroke pathology in hyperlipidemia. Following bone marrow transplantation, mice were fed a high fat diet for 11 weeks, and then subjected to ischemic stroke. Stroke outcome, expression of brain CD36, MCP-1, CCR2, and plasma MCP-1 levels were determined at 3 days post-ischemia. CD36 and CCR2 expression were also determined in splenocytes incubated with serum obtained from CD36-expressing or CD36-deficient mice. Infiltrating immune cells from the periphery are the major source of CD36 in the post-ischemic brain and contribute to stroke-induced brain injury. This CD36 effect was dependent on the modulation of MCP-1 and CCR2 expression in peripheral immune cells as well as CD36-expressing cells in the host brain. This study demonstrates that CD36 expressed in the periphery and brain synergize in ischemic brain injury through regulation of the MCP-1/CCR2 chemokine axis in hyperlipidemic conditions.
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影响因子: 4.8
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发表时间: 2000-04-01
影响因子: 15.9
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