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首页> 外文期刊>American Journal of Physiology >Macrophage-derived apolipoprotein E ameliorates dyslipidemia and atherosclerosis in obese apolipoprotein E-deficient mice
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Macrophage-derived apolipoprotein E ameliorates dyslipidemia and atherosclerosis in obese apolipoprotein E-deficient mice

机译：巨噬细胞衍生的载脂蛋白E减轻肥胖载脂蛋白E缺乏症小鼠的血脂异常和动脉粥样硬化

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First published November 20, 2007; doi:10.1152/ajpendo.00601.2007.-Previous studies have demonstrated that macrophage-derived apolipoprotein E (apoE) reduces atherosclerotic lesion formation in lean apoE-deficient (-/-) mice. apoE has also been demonstrated to play a role in adipocyte differentiation and lipid accumulation. Because the prevalence of obesity has grown to epidemic proportions, we sought to determine whether macrophage-derived apoE could impact atherosclerotic lesion formation or adipose tissue expansion and inflammation in obese apoE~(-/-) mice. To this end, we transplanted obese leptin-deficient (pb/ob) apoE~(-/-) mice with bone marrow from either ob/ob;apoE~(-/-) or ob/ob;apoE~(+/+) donors. There were no differences in body weight, total body adipose tissue, or visceral fat pad mass between recipient groups. The presence of macrophage-apoE had no impact on adipose tissue macrophage content or inflammatory cytokine expression. Recipients of apoE~(+/+) marrow demonstrated 3.7-fold lower plasma cholesterol (P < 0.001) and 1.7-fold lower plasma triglyceride levels (P < 0.01) by 12 wk after transplantation even though apoE was present in plasma at concentrations <10% of wild-type levels. The reduced plasma lipids reflected a dramatic decrease in very low density lipoprotein and a mild increase in high-density lipoprotein levels. Atherosclerotic lesion area was > 10-fold lower in recipients of ob/ob;apoE~(+/+) marrow (P < 0.005). Similar results were seen in leptin receptor-deficient (dbldb) apoE~~(-/-) mice. Finally, when bone marrow transplantation was performed in 4-mo-old ob/ob;oE~(-/-) and db/db;apoE~(-/-) mice with preexisting lesions, recipients of apoE~(+/+) marrow had a 2.8-fold lower lesion area than controls (P = 0.0002). These results demonstrate that macrophage-derived apoE does not impact adipose tissue expansion or inflammatory status; however, even very low levels of macrophage-derived apoE are capable of reducing plasma lipids and atherosclerotic lesion area in obese mice.
机译：首次发布于2007年11月20日; doi：10.1152 / ajpendo.00601.2007.-以前的研究表明，巨噬细胞衍生的载脂蛋白E（apoE）减少了瘦apoE缺陷（-/-）小鼠的动脉粥样硬化病变的形成。还证明了载脂蛋白E在脂肪细胞分化和脂质蓄积中起作用。由于肥胖的患病率已上升到流行的程度，我们试图确定巨噬细胞衍生的apoE是否会影响肥胖apoE〜（-/-）小鼠的动脉粥样硬化病变形成或脂肪组织扩张和炎症。为此，我们从ob / ob; apoE〜（-/-）或ob / ob; apoE〜（+ / +）移植了肥胖瘦素缺陷型（pb / ob）apoE〜（-/-）小鼠骨髓）捐助者。接受者组之间的体重，全身脂肪组织或内脏脂肪垫质量无差异。巨噬细胞-apoE的存在对脂肪组织巨噬细胞含量或炎性细胞因子表达没有影响。即使在血浆中载有apoE的浓度达到12 wk，载脂蛋白〜（+ / +）骨髓的受者在移植后12 wk仍可降低3.7倍血浆胆固醇（P <0.001）和1.7倍降低血浆甘油三酸酯水平（P <0.01）。野生型水平的10％。血浆脂质的减少反映了极低密度脂蛋白的急剧下降和高密度脂蛋白水平的温和上升。 ob / ob; apoE〜（+ / +）骨髓接受者的动脉粥样硬化病变面积降低了10倍以上（P <0.005）。在瘦素受体缺陷型（dbldb）apoE〜（-/-）小鼠中观察到了相似的结果。最后，当在具有病变的4个月大ob / ob; oE〜（-/-）和db / db; apoE〜（-/-）小鼠中进行骨髓移植时，apoE〜（+ / + ）的病变面积比对照组低2.8倍（P = 0.0002）。这些结果表明，巨噬细胞衍生的apoE不会影响脂肪组织的扩张或炎症状态。然而，即使是非常低水平的巨噬细胞源性载脂蛋白E，也能够减少肥胖小鼠的血脂和动脉粥样硬化病变区域。

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