Hiltunen T P, Luoma J S, Nikkari T, Ylä-Herttuala S
Department of Medical Biochemistry, University of Tampere Medical School, Tampere University Hospital, Finland.
Circulation. 1998 Mar 24;97(11):1079-86. doi: 10.1161/01.cir.97.11.1079.
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.
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 3-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.
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.
动脉粥样硬化病变包含泡沫细胞，这些泡沫细胞由单核细胞 - 巨噬细胞和平滑肌细胞（SMC）通过过度摄取脂蛋白而产生。脂质蓄积存在许多候选受体，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的表达，定量信息很少。
采用竞争性逆转录 - 聚合酶链反应和原位杂交技术，对新西兰白兔（NZW）和渡边遗传性高脂血症（WHHL）兔的主动脉内膜 - 中膜进行研究。给NZW兔喂食含1%胆固醇的饲料0周（对照组）、3周、6周或14周。所有组的主动脉内膜 - 中膜中LDLR mRNA表达均较低。在所分析的受体中，LRP在对照组中表达最高，其mRNA在14周组中诱导了三倍，该组主动脉有广泛病变。对照组中SR表达低，VLDLR表达中等。在喂食胆固醇期间，这两种受体均被高度诱导（SRs在3周和14周组分别诱导3倍和270倍；VLDLR分别诱导15倍和100倍）。从WHHL兔获得了类似结果：正常内膜 - 中膜中LRP mRNA基础水平高；在脂肪条纹和脂肪斑块中，LRP中度诱导，SRs和VLDLR明显诱导。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。仅在巨噬细胞中检测到SR表达。
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和巨噬细胞源性泡沫细胞的形成，而SRs在巨噬细胞脂质摄取中起重要作用。
