Amelioration of Hypertriglyceridemia with Hypo-Alpha-Cholesterolemia in LPL Deficient Mice by Hematopoietic Cell-Derived LPL
Amelioration of Hypertriglyceridemia with Hypo-Alpha-Cholesterolemia in LPL Deficient Mice by Hematopoietic Cell-Derived LPL
复制标题
通过造血细胞源性 LPL 改善 LPL 缺陷小鼠的高甘油三酯血症和低 α 胆固醇血症
DOI：
10.1371/journal.pone.0025620
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发表时间：
2011-09-29
期刊：
影响因子：
3.7
通讯作者：
Liu, George
中科院分区：
文献类型：
--
作者：
Ding, Yinyuan;Zhang, Ling;Liu, George
背景资料：巨噬细胞衍生的脂蛋白脂酶（LPL）已被一致地显示为促进动脉粥样硬化病变的形成，而其影响血浆脂质和脂蛋白水平的程度在野生型和高胆固醇血症小鼠中不同。众所周知，大量脂肪组织和骨骼肌中高水平的LPL肯定会掩盖巨噬细胞LPL对血浆脂蛋白代谢的贡献。因此，我们选择LPL缺陷（LPL（-/-））小鼠作为替代模型，通过骨髓移植评估巨噬细胞LPL在血浆脂蛋白代谢中的作用，通过骨髓移植LPL将主要由造血细胞来源的巨噬细胞产生。方法和结果：对高脂血症LPL（-/-）小鼠进行致死性照射，然后分别移植野生型（LPL（+/+））或LPL（-/-）小鼠的骨髓。16周后，LPL（+/+）-> LPL（-/-）小鼠的血浆甘油三酯和胆固醇水平显著降低（408 +/- 44.9对比2.7 +/- 0.5 × 10（3）和82.9 +/- 7.1对比229.1 +/- 30.6 mg/dl，p LPL（-/-）小鼠比LPL（-/-）-> LPL（-/-）小鼠更快，但比野生型小鼠慢。与LPL（-/-）-> LPL（-/-）小鼠相比，LPL（+/+）-> LPL（-/-）小鼠的肝脏甘油三酯含量也显著增加（6.8 +/- 0.7 vs 4.6 +/- 0.5 mg/g湿组织，p
Background: Macrophage-derived lipoprotein lipase (LPL) has been shown uniformly to promote atherosclerotic lesion formation while the extent to which it affects plasma lipid and lipoprotein levels varies in wild-type and hypercholesterolemic mice. It is known that high levels of LPL in the bulk of adipose tissue and skeletal muscle would certainly mask the contribution of macrophage LPL to metabolism of plasma lipoprotein. Therefore, we chose LPL deficient (LPL(-/-)) mice with severe hypertriglyceridemia as an alternative model to assess the role of macrophage LPL in plasma lipoprotein metabolism via bone marrow transplant, through which LPL will be produced mainly by hematopoietic cell-derived macrophages.Methods and Results: Hypertriglyceridemic LPL(-/-) mice were lethally irradiated, then transplanted with bone marrow from wild-type (LPL(+/+)) or LPL(-/-) mice, respectively. Sixteen weeks later, LPL(+/+) -> LPL(-/-) mice displayed significant reduction in plasma levels of triglyceride and cholesterol (408 +/- 44.9 vs. 2.7 +/- 0.5 x10(3) and 82.9 +/- 7.1 vs. 229.1 +/- 30.6 mg/dl, p LPL(-/-) mice was faster than that in LPL(-/-) -> LPL(-/-) mice, but slower than that in wild-type mice. Liver triglyceride content in LPL(+/+) -> LPL(-/-) mice was also significantly increased, compared with LPL(-/-) -> LPL(-/-) mice (6.8 +/- 0.7 vs. 4.6 +/- 0.5 mg/g wet tissue, p