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Roles of signal transmitters in vascular endothelial injury by activated platalets and its prevention

信号传导分子在活化血小板损伤血管内皮细胞中的作用及其预防

基本信息

批准号：
02670387
负责人：
KISHI Yukio
金额：
$ 1.22万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

项目摘要

An in vitro study was performed to assess injury to vascular endothelial cells. Human platelets, activated by collagen, enhanced the leakage of radioactivity from cultured bovine aortic endothelial cells preloaded with[^3H]adenine ([^3H]adenine release). An analysis of radioactive materials by thin-layer chromatography revealed decreased intracellular ATP content in the cells treated with activated platelets. The medium contained AMP and adenosine, the latter increasing following the treatment of the cells. The[^3H]cyclic AMP showed time-dependent decrease in the prelabeled cells, exposed to the activated platelets. Moreover, activated platelets induced increase in inositol triphosphate- and cytosolic free calcium ion in the endothelial cells. The initial rapid increase in calcium concentration forming a spike was abolished when the activated platelets were pretreated with apyrase. Pretreatment of the endothelial cells with agents elevating the cyclic AMP levels prevented a [^3H]adenine release, while nifedipine or agents which produce effects that increase cyclic GMP levels had little effects.We conclude that calcium ion plays an important role in vascular endothelial injury by activated platelets and agents elevating cyclic AMP may protect the cells from injury by enhancing calcium sequestration.

进行体外研究以评估对血管内皮细胞的损伤。胶原蛋白激活的人血小板增强了预先加入[^3H]腺嘌呤的培养牛主动脉内皮细胞的放射性泄漏（[^3H]腺嘌呤释放）。通过薄层色谱法对放射性物质进行分析，发现用活化血小板处理的细胞中细胞内ATP含量降低。培养基中含有AMP和腺苷，后者在处理细胞后增加。在暴露于活化血小板的预标记细胞中，[^3H]环AMP呈时间依赖性降低。此外，活化的血小板诱导增加肌醇三磷酸-和胞浆游离钙离子在内皮细胞。当用腺苷三磷酸双磷酸酶预处理活化的血小板时，形成尖峰的钙浓度的初始快速增加被取消。用提高环磷酸腺苷水平的药物预处理内皮细胞可阻止[^3H]腺嘌呤的释放，而硝苯地平或能提高环磷酸鸟苷水平的药物则几乎没有作用。我们的结论是，钙离子在活化血小板引起的血管内皮损伤中起重要作用，提高环磷酸腺苷水平的药物可能通过增强钙的螯合作用来保护细胞免受损伤。