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

Background-Atherosclerotic lesions contain foam cells that arise from monocyte-macrophages and smooth muscle cells (SMCs) by excessive uptak e of lipoproteins. There are many candidate receptors for the lipid ac cumulation, such as LDL receptor (LDLR), VLDL receptor (VLDLR), LDL re ceptor-related protein (LRP), and scavenger receptors (SRs). However, little quantitative information exists on the expression of these rece ptors in normal and atherosclerotic arteries. Methods and Results-Comp etitive reverse transcription-polymerase chain reaction and in situ hy bridization were used for the studies in New Zealand White (NZW) and W atanabe heritable hyperlipidemic (WHHL) rabbit aortic intima-medias. N ZW 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-wee k 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-f old 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 in duction 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 obse rved in endothelial cells. SR expression was detected only in macropha ges. Conclusions-SR and VLDLR mRNAs were highly induced in atheroscler otic lesions. VLDLR and LRP may be involved in the formation of both S MC- and macrophage-derived foam cells, whereas SRs play an important r ole in lipid uptake in macrophages.