ENHANCEMENT BY BERAPROST SODIUM, A STABLE ANALOG OF PROSTACYCLIN, IN THROMBOMODULIN EXPRESSION ON MEMBRANE-SURFACE OF CULTURED VASCULAR ENDOTHELIAL-CELLS VIA INCREASE IN CYCLIC-AMP LEVEL
ENHANCEMENT BY BERAPROST SODIUM, A STABLE ANALOG OF PROSTACYCLIN, IN THROMBOMODULIN EXPRESSION ON MEMBRANE-SURFACE OF CULTURED VASCULAR ENDOTHELIAL-CELLS VIA INCREASE IN CYCLIC-AMP LEVEL
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DOI：
10.1016/0006-2952(91)90651-k
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发表时间：
1991-04-15
影响因子：
5.8
通讯作者：
NAKADATE, T
中科院分区：
文献类型：
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作者：
KAINOH, M;MARUYAMA, I;NAKADATE, T
前列环素和贝前列素钠（贝前列素），前列环素的稳定类似物，以浓度依赖性方式增加培养的人脐静脉内皮细胞（HUVEC）的环腺苷酸（cAMP）水平。贝前列素升高cAMP的持续时间长于前列环素。贝前列素和前列环素均能促进HUVEC膜表面血栓调节蛋白（TM）的表达，且贝前列素促进TM表达的持续性强于前列环素。二丁酰cAMP（db-cAMP）模拟贝前列素的作用和3-异丁基-1-甲基黄嘌呤增强的效果。贝前列素，前列环素和db-cAMP也有效地阻断了白细胞介素-1和肿瘤坏死因子诱导的TM表达的抑制。这些结果表明，TM的表达是由cAMP在HUVEC的正调控，贝前列素可能是通过启动在血管内皮细胞中的cAMP/TM系统的刺激机制，减少血栓形成事件的潜在有效性。
Prostacyclin and beraprost sodium (beraprost), a stable analogue of prostacyclin, increased cyclic AMP (cAMP) levels of cultured human umbilical vein endothelial cells (HUVEC) in a concentration-dependent manner. The elevation of cAMP by beraprost was sustained longer than that by prostacyclin. The expression of thrombomodulin (TM) on membrane surface of HUVEC was enhanced by beraprost and prostacyclin, and the persistence of the increase in TM expression by beraprost was greater than prostacyclin. Dibutyryl cAMP (db-cAMP) mimicked the effects of beraprost and 3-isobutyl-1-methylxanthine enhanced the effects. Beraprost, prostacyclin and db-cAMP also effectively blocked the interleukin-1- and tumor necrosis factor-induced depression of TM expression substantially. These results suggest that TM expression is positively regulated by cAMP in HUVEC, and that beraprost may be potentially effective for reducing thrombotic events through the mechanism which initiates the stimulation of cAMP/TM system in vascular endothelial cells.