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核心蛋白聚糖在人冠状动脉粥样硬化增厚内膜和平滑肌细胞中的表达

Expression of lumican in thickened intima and smooth muscle cells in human coronary atherosclerosis.

作者信息

Onda Munehiko, Ishiwata Toshiyuki, Kawahara Kiyoko, Wang Ruojiao, Naito Zenya, Sugisaki Yuichi

机构信息

Department of Pathology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.

出版信息

Exp Mol Pathol. 2002 Apr;72(2):142-9. doi: 10.1006/exmp.2002.2425.

Abstract

Lumican is a member of a small leucine-rich proteoglycan family. Members of this family play an important role in cell migration and proliferation during embryonic development, tissue repair, and tumor growth. Lumican is reported to be overexpressed during the wound-healing process in the cornea and ischemic and reperfused heart. Recently, we found that lumican mRNA and its protein are expressed in cultured vascular smooth muscle cells (VSMCs) from the rat aorta. However, the expression and role of lumican in human atherosclerotic tissues are not clearly elucidated. In the present study, we aimed to clarify whether lumican is expressed in VSMCs and its localization in human coronary atherosclerotic tissues. The lumican protein and its mRNA were expressed in a small number of VSMCs in the media of normal coronary artery, but the lumican protein was not localized in the medial stroma. In contrast, the lumican protein and its mRNA were expressed in most of VSMCs that migrated into the thickened intima, but not in infiltrating foamy macrophages. The lumican protein was prominently localized in the thickened intimal stroma. The lumican protein and its mRNA were also expressed in VSMCs in the inner layer of the media and its protein was localized in medial stromal tissues. These findings indicate that the lumican protein is mainly synthesized by intimal and medial VSMCs in coronary atherosclerosis and that lumican contributes to collagen fibrillogenesis of coronary atherosclerosis.

摘要

角膜蛋白聚糖是富含亮氨酸的小分子蛋白聚糖家族的成员之一。该家族成员在胚胎发育、组织修复和肿瘤生长过程中的细胞迁移和增殖中发挥重要作用。据报道,在角膜伤口愈合过程以及缺血再灌注心脏中,角膜蛋白聚糖表达上调。最近,我们发现角膜蛋白聚糖的信使核糖核酸(mRNA)及其蛋白在大鼠主动脉培养的血管平滑肌细胞(VSMC)中表达。然而,角膜蛋白聚糖在人类动脉粥样硬化组织中的表达及作用尚未明确阐明。在本研究中,我们旨在明确角膜蛋白聚糖是否在VSMC中表达及其在人类冠状动脉粥样硬化组织中的定位。在正常冠状动脉中膜的少数VSMC中表达了角膜蛋白聚糖蛋白及其mRNA,但角膜蛋白聚糖蛋白并不定位于中膜基质。相反,在迁移至增厚内膜的大多数VSMC中表达了角膜蛋白聚糖蛋白及其mRNA,但在浸润的泡沫巨噬细胞中未表达。角膜蛋白聚糖蛋白显著定位于增厚的内膜基质中。在中膜内层的VSMC中也表达了角膜蛋白聚糖蛋白及其mRNA,其蛋白定位于中膜基质组织中。这些发现表明,在冠状动脉粥样硬化中,角膜蛋白聚糖蛋白主要由内膜和中膜的VSMC合成,并且角膜蛋白聚糖有助于冠状动脉粥样硬化的胶原纤维形成。

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