Atherosclerosis in C3H/HeJ Mice Reconstituted With Apolipoprotein E-Null Bone Marrow

Weibin Shi, Xuping Wang, Khan Tangchitpiyanond, Jack Wong, Yi-Shou Shi, A. Lusis
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引用次数: 29

Abstract

Previous studies showed that reconstitution of atherosclerosis-susceptible C57BL/6 (B6) female mice with apolipoprotein E (apoE)-deficient (apoE−/−) bone marrow resulted in markedly increased atherosclerosis, despite the fact that plasma lipid levels were unchanged. To determine whether apoE−/− bone marrow would increase atherosclerosis in an atherosclerosis-resistant strain, female C3H/HeJ (C3H) mice were lethally irradiated and reconstituted with bone marrow from either C3H.apoE−/− mice or wild-type C3H mice. Four weeks after transplantation, the mice were fed an atherogenic diet for 12 weeks. We found that reconstitution of C3H mice with apoE−/− bone marrow resulted in a slight reduction in plasma apoE levels and a dramatic reduction in apoE and apolipoprotein B (apoB) in the aortic wall. Plasma apoB and cholesterol levels were unchanged, as were atherosclerotic lesions at the aortic root. These data indicate that reconstitution of C3H mice with apoE−/− bone marrow has no effect on atherosclerosis susceptibility and that apoE promotes accumulation of apoB in the vessel wall.
载脂蛋白E-Null骨髓重建C3H/HeJ小鼠的动脉粥样硬化
先前的研究表明,尽管血浆脂质水平不变,但载脂蛋白E (apoE)-缺陷(apoE−/−)骨髓重构易感的C57BL/6 (B6)雌性小鼠的动脉粥样硬化明显增加。为了确定apoE−/−骨髓是否会增加动脉粥样硬化抵抗品系的动脉粥样硬化,对雌性C3H/HeJ (C3H)小鼠进行致命照射,并用C3H的骨髓重组。apoE−/−小鼠或野生型C3H小鼠。移植后4周,小鼠喂食致动脉粥样硬化饮食12周。我们发现,用载脂蛋白e−/−骨髓重建C3H小鼠,导致血浆载脂蛋白e水平轻微降低,并显著降低主动脉壁载脂蛋白e和载脂蛋白B (apoB)。血浆载脂蛋白ob和胆固醇水平没有变化,主动脉根部动脉粥样硬化病变也没有变化。这些数据表明,携带apoE−/−骨髓的C3H小鼠重组对动脉粥样硬化易感性没有影响,apoE促进载脂蛋白ob在血管壁的积累。
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