Extracellular matrix glycoprotein biglycan enhances vascular smooth muscle cell proliferation and migration
Extracellular matrix glycoprotein biglycan enhances vascular smooth muscle cell proliferation and migration
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DOI：
10.1161/01.res.0000126049.79800.ca
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发表时间：
2004-04-30
影响因子：
20.1
通讯作者：
Saruta, T
中科院分区：
文献类型：
--
作者：
Shimizu-Hirota, R;Sasamura, H;Saruta, T
蛋白聚糖由血管平滑肌细胞产生和分泌，但这些糖蛋白在血管系统中的病理生理作用是一个谜。由于富含小亮氨酸的蛋白聚糖（SLRP）双糖链蛋白聚糖在动脉病变中过表达，我们产生了在血管平滑肌中组成性过表达双糖链蛋白聚糖的小鼠，以检查对血管病理学的影响。在主动脉和肾血管系统中，与野生型对照组相比，在基础状态和输注血管紧张素II（Ang II）后，转基因小鼠的血管增殖增加。此外，双糖蛋白聚糖过表达和血管紧张素II输注的组合导致冠状动脉中血管平滑肌细胞增殖和迁移的显著增加，以及血管周围纤维化的增加。在体外，双糖蛋白聚糖引起胸苷掺入和血管平滑肌细胞迁移的增加，而在内皮细胞中这些参数没有变化或减少。此外，添加双糖蛋白聚糖导致血管平滑肌细胞中cdk2表达增加和p27水平降低。这些结果表明，这种细胞外基质SLRP可能参与调节血管平滑肌的生长和迁移，通过cdk2和p27依赖的途径。此外，双糖蛋白聚糖表达的变化可能是影响动脉对血管损伤的易感性的一个因素，并且可能在血管病变的发病机制中起直接作用。
Proteoglycans are produced and secreted by vascular smooth muscle cells, but the pathophysiological role of these glycoproteins in the vasculature is an enigma. Because the small leucine-rich proteoglycan (SLRP) biglycan is overexpressed in arteriosclerotic lesions, we produced mice constitutively overexpressing biglycan in the vascular smooth muscle, in order to examine the effects on vascular pathology. In the aorta and renal vasculature, increased vascular proliferation was seen both in the basal state and after infusion of angiotensin II (Ang II) in the transgenic mice compared with wild-type controls. In addition, the combination of biglycan overexpression and Ang II infusion resulted in marked increases in vascular smooth muscle cell proliferation and migration in the coronary arteries, as well as increases in fibrosis surrounding the vessels. In vitro, biglycan caused an increase in thymidine incorporation and migration of vascular smooth muscle cells, whereas these parameters were unchanged or reduced in endothelial cells. Moreover, addition of biglycan resulted in an increase in cdk2 expression and decrease in p27 levels in the vascular smooth muscle cells. These results suggest that this extracellular matrix SLRP may be involved in the regulation of vascular smooth muscle growth and migration through cdk2- and p27-dependent pathways. Furthermore, changes in biglycan expression could be a factor influencing the susceptibility of arteries to vascular injury, and may play a direct role in the pathogenesis of vascular lesions.