巨噬细胞极低密度脂蛋白受体在动脉粥样硬化病变发展中的作用。
Role of the macrophage very-low-density lipoprotein receptor in atherosclerotic lesion development.
作者信息
Eck Miranda Van, Oost Jenina, Goudriaan Jeltje R, Hoekstra Menno, Hildebrand Reeni B, Bos I Sophie T, van Dijk Ko Willems, Van Berkel Theo J C
机构信息
Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
出版信息
Atherosclerosis. 2005 Dec;183(2):230-7. doi: 10.1016/j.atherosclerosis.2005.03.045. Epub 2005 Jun 24.
OBJECTIVES
The very-low-density lipoprotein receptor (VLDLr) is highly expressed in macrophage-rich areas of atherosclerotic lesions. The exact role of the macrophage VLDLr in atherosclerotic lesion development, however, is presently unclear.
METHODS AND RESULTS
To assess the role of the macrophage VLDLr in atherosclerotic lesion development in vivo, we used the technique of bone marrow transplantation to selectively disrupt or reconstitute the VLDLr in macrophages in VLDLr+/+ and VLDLr-/- mice, respectively. After 10 weeks high-cholesterol diet feeding, the lesion area in control transplanted wild-type mice was 17+/-4 x 10(3)+/-microm(2). Disruption of the macrophage VLDLr by transplanting bone marrow from VLDLr-/- mice to wild-type VLDLr+/+ littermates resulted in a tendency to a slight reduction in lesion size to 12+/-3 x 10 microm. The mean atherosclerotic lesion area, measured in control transplanted VLDLr-/- mice, lacking the VLDLr in all tissues was 12+/-3 x 10(3)microm(2). Interestingly, reconstitution of the macrophage VLDLr in VLDLr-deficient recipients resulted in a 2.7-fold increase (P<0.05) in the mean atherosclerotic lesion area to 32+/-3 x 10(3)microm(2).
CONCLUSIONS
The macrophage VLDLr facilitates atherosclerotic lesion development, probably by mediating the accumulation of atherogenic lipoproteins.
目的
极低密度脂蛋白受体（VLDLr）在动脉粥样硬化病变富含巨噬细胞的区域高表达。然而，巨噬细胞VLDLr在动脉粥样硬化病变发展中的确切作用目前尚不清楚。
方法与结果
为了评估巨噬细胞VLDLr在体内动脉粥样硬化病变发展中的作用，我们分别采用骨髓移植技术，选择性地破坏或重建VLDLr+/+和VLDLr-/-小鼠巨噬细胞中的VLDLr。在给予高胆固醇饮食10周后，对照移植野生型小鼠的病变面积为17±4×10³±μm²。通过将VLDLr-/-小鼠的骨髓移植到野生型VLDLr+/+同窝小鼠中破坏巨噬细胞VLDLr，导致病变大小有轻微减小的趋势，降至12±3×10³μm²。在对照移植的VLDLr-/-小鼠中测量的平均动脉粥样硬化病变面积，所有组织均缺乏VLDLr，为12±3×10³μm²。有趣的是，在VLDLr缺陷受体中重建巨噬细胞VLDLr导致平均动脉粥样硬化病变面积增加2.7倍（P<0.05），达到32±3×10³μm²。
结论
巨噬细胞VLDLr可能通过介导致动脉粥样硬化脂蛋白的积聚促进动脉粥样硬化病变发展。
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