Role of macrophage-derived lipoprotein lipase in lipoprotein metabolism and atherosclerosis
Role of macrophage-derived lipoprotein lipase in lipoprotein metabolism and atherosclerosis
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DOI：
10.1161/01.atv.20.9.e53
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发表时间：
2000-09-01
影响因子：
8.7
通讯作者：
Van Berkel, TJC
中科院分区：
文献类型：
--
作者：
Van Eck, M;Zimmermann, R;Van Berkel, TJC
巨噬细胞合成脂蛋白脂酶（LPL）在早期动脉粥样硬化形成中上调，暗示LPL可能参与斑块形成。然而，巨噬细胞源性LPL在动脉粥样硬化病变发展中是否具有促动脉粥样硬化或抗动脉粥样硬化作用尚不清楚。在这项研究中，巨噬细胞衍生的LPL对脂质代谢和动脉粥样硬化的作用进行了评估，在体内LPL缺陷（LPL-/-）和野生型（LPL+/+）骨髓移植到C57 BL/6小鼠。骨髓移植（BMT）后8周，LPL-/->、C57 BL/6小鼠的血清胆固醇水平与LPL+/+--> C57 BL/6小鼠相比降低了8%（PC 57 BL/6小鼠分别降低了5倍和9倍，导致在两种饮食条件下与对照组相比差异接近50%（PC 57 BL/6小鼠）。高胆固醇饮食3个月后，LPL-/--> C57 BL/6小鼠的动脉粥样硬化病变面积与对照组相比减少了52%。可以得出结论，巨噬细胞衍生的LPL在调节血清胆固醇、载脂蛋白E和动脉粥样硬化形成中起着重要作用，这表明特异性阻断巨噬细胞LPL的产生可能有利于减少动脉粥样硬化病变的发展。
Lipoprotein lipase (LPL) synthesis by macrophages is upregulated in early atherogenesis, implicating the possible involvement of LPL in plaque formation. However, it is still unclear whether macrophage-derived LPL displays a proatherosclerotic or an antiatherosclerotic role in atherosclerotic lesion development. In this study, the role of macrophage-derived LPL on lipid metabolism and atherosclerosis was assessed in vivo by transplantation of LPL-deficient (LPL-/-) and wild-type (LPL+/+) bone marrow into C57BL/6 mice. Eight weeks after bone marrow transplantation (BMT), serum cholesterol levels in LPL-/- -->,C57BL/6 mice were reduced by 8% compared with those in LPL+/+-->C57BL/6 mice (PC57BL/6 mice 5-fold and 9-fold, respectively, resulting in a difference of approximate to 50% (PC57BL/6 mice compared with controls under both dietary conditions. After 3 months on a high-cholesterol diet, the atherosclerotic lesion area in LPL-/-->C57BL/6 mice was reduced by 52% compared with controls. It can be concluded that macrophage-derived LPL plays a significant role in the regulation of serum cholesterol, apolipoprotein E, and atherogenesis, suggesting that specific blockade of macrophage LPL production may be beneficial for decreasing atherosclerotic lesion development.