Luoma J, Hiltunen T, Särkioja T, Moestrup S K, Gliemann J, Kodama T, Nikkari T, Ylä-Herttuala S
Department of Biomedical Sciences, University of Tampere, Finland.
J Clin Invest. 1994 May;93(5):2014-21. doi: 10.1172/JCI117195.
Macrophage- and smooth muscle cell (SMC)-derived foam cells are typical constituents of human atherosclerotic lesions. At least three receptor systems have been characterized that could be involved in the development of foam cells: alpha 2-macroglobulin receptor/LDL receptor-related protein (alpha 2 MR/LRP), scavenger receptor, and LDL receptor. We studied the expression of these receptors in human atherosclerotic lesions with in situ hybridization and immunocytochemistry. An abundant expression of alpha 2MR/LRP mRNA and protein was found in SMC and macrophages in both early and advanced lesions in human aortas. alpha 2MR/LRP was also present in SMC in normal aortas. Scavenger receptor mRNA and protein were expressed in lesion macrophages but no expression was found in lesion SMC. LDL receptor was absent from the lesion area but was expressed in some aortas in medial SMC located near the adventitial border. The results demonstrate that (a) alpha 2MR/LRP is, so far, the only lipoprotein receptor expressed in lesions SMC in vivo; (b) scavenger receptors are expressed only in lesion macrophages; and (c) both receptors may play important roles in the development of human atherosclerotic lesions.
巨噬细胞和平滑肌细胞(SMC)来源的泡沫细胞是人类动脉粥样硬化病变的典型组成部分。至少已鉴定出三种可能参与泡沫细胞形成的受体系统:α2-巨球蛋白受体/LDL受体相关蛋白(α2MR/LRP)、清道夫受体和LDL受体。我们用原位杂交和免疫细胞化学方法研究了这些受体在人类动脉粥样硬化病变中的表达情况。在人类主动脉的早期和晚期病变中,SMC和巨噬细胞中均发现α2MR/LRP mRNA和蛋白大量表达。α2MR/LRP在正常主动脉的SMC中也有表达。清道夫受体mRNA和蛋白在病变巨噬细胞中表达,但在病变SMC中未发现表达。病变区域不存在LDL受体,但在一些主动脉外膜边界附近的中膜SMC中有表达。结果表明:(a)迄今为止,α2MR/LRP是体内病变SMC中唯一表达的脂蛋白受体;(b)清道夫受体仅在病变巨噬细胞中表达;(c)这两种受体可能在人类动脉粥样硬化病变的形成中起重要作用。