MECHANISM OF SHEAR-INDUCED PROSTACYCLIN PRODUCTION IN ENDOTHELIAL-CELLS
MECHANISM OF SHEAR-INDUCED PROSTACYCLIN PRODUCTION IN ENDOTHELIAL-CELLS
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DOI：
10.1016/s0006-291x(89)80172-x
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发表时间：
1989-01-16
影响因子：
3.1
通讯作者：
FRANGOS, JA
中科院分区：
文献类型：
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作者：
BHAGYALAKSHMI, A;FRANGOS, JA
将汇合的人脐静脉内皮细胞置于稳定的剪切流中。之前的研究表明，流量会诱导前列环素产生的爆发，然后持续刺激前列环素的产生，使其比基础水平高出数倍（1）。在EGTA的存在下，前列环素的生产被抑制在稳态阶段的74%。用quin 2/AM预孵育内皮细胞，在这里用作细胞内钙螯合剂，也抑制前列环素的产生（83%）。细胞内钙动员的抑制没有显著影响。孵育细胞与硝苯地平，电压操作通道阻滞剂，剪切诱导前列环素的生产没有影响，而布洛芬减少剪切诱导前列环素的生产。RHC-80267是一种甘油二酯脂肪酶抑制剂，可抑制66%剪切诱导的PGI_2产生。我们的研究结果表明，细胞外和细胞内的Ca 2+是必要的，磷脂酶C途径可能是主要来源，释放花生四烯酸在剪切诱导前列环素的生产。
Human umbilical vein endothelial cells at confluence were subjected to steady shear flow. It was previously shown that flow induced a burst in prostacyclin production followed by a sustained stimulation of production of several fold higher than basal levels (1). In the presence of EGTA, prostacyclin production was inhibited in the steady state phase by 74%. Preincubation of endothelial cells with quin2/AM, used here as an intracellular calcium chelator, also inhibited the production of prostacyclin (83%). Inhibition of intracellular calcium mobilization had no significant effect. Incubation of cells with nifedipine, a voltage operated channel blocker, had no effect on shear induced prostacyclin production, whereas ibuprofen decreased shear induced prostacyclin production. RHC-80267, a diacylglycerol lipase inhibitor, inhibited 66% of shear induced PGI2 production. Our results suggest that both extracellular and intracellular Ca2+ are necessary and the phospholipase C pathway may be the main source for liberating arachidonic acid in shear induced prostacyclin production.