Expression of LDL receptor, VLDL receptor, LDL receptor-related protein, and scavenger receptor in rabbit atherosclerotic lesions -: Marked induction of scavenger receptor and VLDL receptor expression during lesion development
Expression of LDL receptor, VLDL receptor, LDL receptor-related protein, and scavenger receptor in rabbit atherosclerotic lesions -: Marked induction of scavenger receptor and VLDL receptor expression during lesion development
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DOI：
10.1161/01.cir.97.11.1079
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发表时间：
1998-03-24
期刊：
影响因子：
37.8
通讯作者：
Ylä-Herttuala, S
中科院分区：
文献类型：
--
作者：
Hiltunen, TP;Luoma, JS;Ylä-Herttuala, S
背景-动脉粥样硬化病变含有单核巨噬细胞和平滑肌细胞（SMC）因过度摄取脂蛋白而产生的泡沫细胞。脂质积累的候选受体有很多，如低密度脂蛋白受体（LDLR）、极低密度脂蛋白受体（VLDLR）、低密度脂蛋白受体相关蛋白（LRP）和清道夫受体（SRs）。然而，关于这些受体在正常和动脉粥样硬化动脉中表达的定量信息很少。 方法和结果-竞争性逆转录聚合酶链反应和原位杂交用于新西兰白兔（NZW）和渡边遗传性高脂血症（WHHL）兔主动脉内膜中膜的研究。 NZW 兔饲喂 1% 胆固醇饮食 0（对照组）、3、6 或 14 周。所有组的主动脉内膜中层 LDLR mRNA 表达均较低。在分析的受体中，LRP在对照组中表达最高，其mRNA在主动脉广泛病变的14周组中被诱导三倍。对照组SR表达较低，VLDLR表达中等。两种受体在胆固醇喂养期间均被高度诱导（SR，在 S 周组和 14 周组中分别诱导 3 倍和 270 倍；VLDLR，分别诱导 15 倍和 100 倍）。从 WHHL 兔中获得了类似的结果：正常内膜中层中基础 LRP mRNA 较高；在脂肪条纹和脂肪斑块中中度诱导 LRP 并显着诱导 SR 和 VLDLR。原位杂交表明LRP和VLDLR在SMC和巨噬细胞中表达。在内皮细胞中也观察到 VLDLR 表达。 SR仅在巨噬细胞中检测到表达。结论-SR和VLDLR mRNA在动脉粥样硬化病变中高度诱导。 VLDLR 和 LRP 可能参与 SMC 和巨噬细胞来源的泡沫细胞的形成，而 SR 在巨噬细胞的脂质摄取中发挥重要作用。
Background-Atherosclerotic lesions contain foam cells that arise from monocyte-macrophages and smooth muscle cells (SMCs) by excessive uptake of lipoproteins. There are many candidate receptors for the lipid accumulation, such as LDL receptor (LDLR), VLDL receptor (VLDLR), LDL receptor-related protein (LRP), and scavenger receptors (SRs). However, little quantitative information exists on the expression of these receptors in normal and atherosclerotic arteries.Methods and Results-Competitive reverse transcription-polymerase chain reaction and in situ hybridization were used for the studies in New Zealand White (NZW) and Watanabe heritable hyperlipidemic (WHHL) rabbit aortic intima-medias. NZW rabbits were fed a 1% cholesterol diet for 0 (control group), 3, 6, or 14 weeks. LDLR mRNA expression was low in aortic intima-medias of all groups. Of the analyzed receptors, LRP had the highest expression in the control group, and its mRNA was induced threefold in the 14-week group, the aortas of which had extensive lesions. SR expression was low and VLDLR expression moderate in the control group. Both receptors were highly induced during cholesterol feeding (SRs, 3-fold and 270-fold induction; VLDLR, 15-fold and 100-fold induction in the S-week and 14-week groups, respectively). Comparable results were obtained from WHHL rabbits: high basal LRP mRNA in normal intima-medias; moderate induction of LRP and marked induction of SRs and VLDLR in fatty streaks and fatty plaques. In situ hybridization indicated that LRP and VLDLR were expressed in SMCs and macrophages. VLDLR expression was also observed in endothelial cells. SR expression was detected only in macrophages.Conclusions-SR and VLDLR mRNAs were highly induced in atherosclerotic lesions. VLDLR and LRP may be involved in the formation of both SMC- and macrophage-derived foam cells, whereas SRs play an important role in lipid uptake in macrophages.