Enhancement by homocysteine of plasminogen activator inhibitor-1 gene expression and secretion from vascular endothelial and smooth muscle cells
Enhancement by homocysteine of plasminogen activator inhibitor-1 gene expression and secretion from vascular endothelial and smooth muscle cells
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DOI：
10.1006/bbrc.2000.2753
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发表时间：
2000-05-27
影响因子：
3.1
通讯作者：
Watanabe, T
中科院分区：
文献类型：
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作者：
Midorikawa, S;Sanada, H;Watanabe, T
为了阐明同型半胱氨酸与纤溶系统的关系，我们研究了同型半胱氨酸对体外培养的人血管内皮细胞和平滑肌细胞纤溶酶原激活物抑制剂-1（派-1）和组织型纤溶酶原激活物（tPA）基因表达和蛋白分泌的影响。高半胱氨酸以剂量依赖性方式增强派-1 mRNA和分泌蛋白水平，在浓度大于0.5 mM时观察到对派-1分泌的显着刺激。与此相反，分泌和mRNA表达的tPA没有显着改变同型半胱氨酸刺激。分泌TGF β（转化生长因子β）和TNF α（肿瘤坏死因子α），派-1的表达和分泌的可能调节剂，没有刺激治疗与1.0 mM同型半胱氨酸。这些结果表明，高同型半胱氨酸血症诱导的动脉粥样硬化和/或血栓形成可能是由同型半胱氨酸诱导的派-1基因的表达和分泌的刺激，在血管系统中通过独立于TGF β和TNF α的旁分泌-自分泌活性的机制。(C)北京大学出版社.
In order to elucidate the relationship between homocysteine and the fibrinolytic system, we examined the effect of homocysteine on plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (tPA) gene expression and protein secretion in cultured human vascular endothelial and smooth muscle cells in vitro. PAI-1 mRNA and secreted protein levels were both enhanced by homocysteine in a dose dependent manner, with significant stimulation of PAI-1 secretion observed at concentrations greater than 0.5 mM homocysteine. In contrast, secretion and mRNA expression of tPA were not significantly altered by homocysteine stimulation. Secretion of TGF beta (transforming growth factor beta) and TNF alpha (tumor necrosis factor alpha), possible regulators of PAI-1 expression and secretion, were not stimulated by treatment with 1.0 mM homocysteine. These results suggests that hyperhomocysteinemia-induced atherosclerosis and/or thrombosis may be caused by homo cysteine-induced stimulation of PAI-1 gene expression and secretion in the vasuculatures by a mechanism independent from paracrine-autocrine activity of TGF beta and TNF alpha. (C) 2000 Academic Press.