Transplantation of monocyte CC-chemokine receptor 2-deficient bone marrow into ApoE3-Leiden mice inhibits atherogenesis

Transplantation of monocyte CC-chemokine receptor 2-deficient bone marrow into ApoE3-Leiden mice inhibits atherogenesis
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DOI:
10.1161/01.atv.0000058431.78833.f5
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发表时间:
2003-03-01
影响因子:
8.7
通讯作者:
Van Berkel, TJC
Van Berkel, TJC
中科院分区:
医学1区
文献类型:
--
作者:
Guo, J;Van Eck, M;Van Berkel, TJC

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目的-确定白细胞CC趋化因子受体2 (CCR2)在动脉粥样硬化早期发展中的作用方法和结果-从CCR2 (-/-)和CCR2 (+/+)小鼠采集的骨髓细胞移植到ApoE3-Leiden小鼠中,ApoE3-Leiden小鼠是一种对饮食引起的动脉粥样硬化敏感的小鼠品系。骨髓移植后8周,将普通饲料改为高胆固醇饮食(1%胆固醇、15%脂肪、0.5%胆酸盐),再持续8周,以诱发动脉粥样硬化。 CCR2 (+/+) --> ApoE3-Leiden 小鼠和 CCR2 (-/-) --> ApoE3-Leiden 小鼠之间的血清胆固醇和甘油三酯水平没有观察到显着差异。然而,CCR2 (-/-) --> ApoE3-Leiden 小鼠的平均主动脉根部病变面积仅为 2.94+/-1.94x10(4) mum(2),而 CCR2 (+/+) --> ApoE3-Leiden 小鼠的平均主动脉根部病变面积为 20.94+/-12.71x10(4) mum(2)。因此,与对照相比,白细胞上 CCR2 的缺失导致主动脉病变面积减少 86%(n=10,P
Objective-To determine the role of leukocyte CC-chemokine receptor 2 (CCR2) in the early development of atherosclerosisMethods and Results-Bone marrow cells harvested from CCR2 (-/-) and CCR2 (+/+) mice were transplanted into ApoE3-Leiden mice, a mouse strain susceptible for diet-induced atherosclerosis. Eight weeks after bone marrow transplantation, the diet of regular chow was switched to a high-cholesterol diet (1% cholesterol, 15% fat, 0.5% cholate) for another 8 weeks to induce atherosclerosis. No significant differences in serum cholesterol and triglyceride levels were observed between the CCR2 (+/+) --> ApoE3-Leiden and CCR2 (-/-) --> ApoE3-Leiden mice. However, the mean cross-sectional aortic root lesion area of CCR2 (-/-) --> ApoE3-Leiden mice was only 2.94+/-1.94x10(4) mum(2) compared with 20.94+/-12.71x10(4) mum(2), for CCR2 (+/+) --> ApoE3-Leiden mice. Thus, the absence of CCR2 on leukocytes induces an 86% reduction of aortic lesion area as compared with controls (n=10, P