Analysis of new lipoprotein receptors using animal models

属于低密度脂蛋白受体（LDLR）家族的受体被认为在动脉壁以及其他器官（如肝脏和肾上腺）的脂蛋白代谢中起关键作用。在这里，我们报告了一种新的镶嵌LDLR家族成员的表达，我们和其他人发现，我们称之为LR 11，显着诱导动脉粥样硬化形成的动物模型的过程中。RT-PCR和RNase保护实验表明，胆固醇喂养诱导兔动脉粥样硬化斑块LR 11 mRNA表达。免疫组织化学分析显示，最诱导的LR 11表达定位于内膜，特别是内膜平滑肌细胞（SMC），以及微弱的表达在靠近动脉粥样硬化病变内膜边界的中膜SMC。内皮剥脱引起的实验性内膜增生显示，损伤后LR 11 mRNA在动脉中大量表达，其转录本主要定位于增生的内膜和中层。提示LR 11的调控表达可能在动脉粥样硬化病变发展过程中对内膜和中膜SMC的病理功能起重要作用。镶嵌型LDLR家族成员的显著诱导可能为高表达LDLR家族成员在动脉粥样硬化中的未知功能意义提供新的线索，该家族成员已被认为是多功能受体。

The receptors belonging to the low density lipoprotein receptor (LDLR) family are thought to play key roles in lipoprotein metabolism at arterial walls as well as other organs, such as liver and adrenal glands. Here, we report that the expression of a novel mosaic LDLR family member, discovered by us and others, which we termed LR11, is markedly induced in the process of atherosclerosis formation of animal models. RT-PCR and RNase protection assay showed that the LR11 mRNA expression is induced in rabbit atherosclerotic aortas after cholesterol feeding. Immunohistochemical analyses revealed that the most induced LR11 expression is localized in intima, particularly over intimal smooth muscle cells (SMCs), as well as faint expression on medial SMCs close to the intimal border at the atheromatous lesions. Experimental intimal hyperplasia by endothelial denudation showed that the LR11 mRNA was much expressed at the arteries after the injury, and the transcripts were mostly localized at the hyperplastic intima as well as medial layer. These findings suggest that the regulatory expression of LR11 might be important for the pathological functions of intimal and medial SMCs during arteriosclerotic lesion developoment. Marked induction of the mosaic LDLR family member is likely to shed new light on the yet unknown functional significance of the highly expressed LDLR family members in atheroma, which have been suggested as multifunctional receptors.