血管内皮细胞合成和分泌Perlecan,一种大的硫酸乙酰肝素蛋白聚糖,通过诱导抗凝血酶III和增强成纤维细胞生长因子(FGF)-2活性来增加血管内皮的抗凝血活性,从而促进动脉粥样硬化进展过程中受损内皮的迁移和增殖。然而,内皮perlecan表达的确切调控机制尚不清楚.由于有机-无机混合分子作为分析生物系统的工具正在迅速发展,我们使用有机锑化合物库搜索了一种分子探针来分析这些机理,发现Sb-苯基-N-甲基-5,6,7,12-四氢二苯并[c,f][1,5]azastibocine(PMTAS)分子促进perlecan核心蛋白基因的表达,而不表现出血管内皮细胞的细胞毒性。在本研究中,我们使用生化技术对培养的牛主动脉内皮细胞合成的蛋白聚糖进行了表征。结果表明,PMTAS选择性诱导全细胞核心蛋白合成,而不影响其硫酸乙酰肝素链的形成,在血管内皮细胞中。结果还暗示该过程与内皮细胞密度无关,而在血管平滑肌细胞中,它只发生在高细胞密度。因此,PMTAS将是进一步研究血管细胞中perlecan核心蛋白合成机制的有用工具。这对血管病变的进展至关重要,例如动脉粥样硬化期间的那些。
Vascular endothelial cells synthesize and secrete perlecan, a large heparan sulfate proteoglycan that increases the anticoagulant activity of vascular endothelium by inducing antithrombin III and intensifying fibroblast growth factor (FGF)-2 activity to promote migration and proliferation in the repair process of damaged endothelium during the progression of atherosclerosis. However, the exact regulatory mechanisms of endothelial perlecan expression remain unclear. Since organic-inorganic hybrid molecules are being developed rapidly as tools to analyze biological systems, we searched for a molecular probe to analyze these mechanisms using a library of organoantimony compounds and found that the Sb-phenyl-N-methyl-5,6,7,12-tetrahydrodibenz[c,f][1,5]azastibocine (PMTAS) molecule promotes the expression of perlecan core protein gene without exhibiting cytotoxicity in vascular endothelial cells. In the present study, we characterized proteoglycans synthesized by cultured bovine aortic endothelial cells using biochemical techniques. The results indicated that PMTAS selectively induced perlecan core protein synthesis, without affecting the formation of its heparan sulfate chain, in vascular endothelial cells. The results also implied that this process is independent of the endothelial cell density, whereas in vascular smooth muscle cells, it occurred only at high cell density. Thus, PMTAS would be a useful tool for further studies on the mechanisms underlying perlecan core protein synthesis in vascular cells, which is critical in the progression of vascular lesions, such as those during atherosclerosis.