Vascular smooth muscle cell effect on endothelial cell endothelin-1 production
Vascular smooth muscle cell effect on endothelial cell endothelin-1 production
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DOI：
10.1067/mva.2000.103788
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发表时间：
2000-04-01
影响因子：
4.3
通讯作者：
Powell, RJ
中科院分区：
文献类型：
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作者：
Di Luozzo, G;Bhargava, J;Powell, RJ
内皮素-1（ET-1）是由培养的内皮细胞（EC）分泌的一种强有力的有丝分裂原，是血管病变发展的一个假定因子。本研究的目的是检查平滑肌细胞（SMC）是否抑制EC分泌ET-1。采用双层共培养模型检测平滑肌细胞对EC ET-1和组成型表达的一氧化氮（NO）合酶活性的影响。与单独培养的EC相比，SMC抑制EC ET-1蛋白和RNA水平。与单独培养的EC相比，SMC增加EC NO的产生。NO合成酶抑制剂N-硝基-L-精氨酸甲酯可阻断SMC对EC ET-1产生的抑制作用。EC刺激SMC增殖，ET-1 AB和B受体阻断剂抑制EC刺激SMC增殖。ET-1A阻断剂对SMC增殖无明显影响.我们的结论是SMC调节EC ET-1和ecNOS合酶的转录水平和蛋白水平。SMC抑制内皮细胞产生ET-1可能是通过SMC调节内皮细胞NO活性的变化来介导的。最后，EC刺激双层共培养的SMC增殖是由ET-1通过ET-1 B受体介导的。
Endothelin-1 (ET-1) is a potent mitogen secreted by endothelial cells (ECs) in culture and is a putative factor in vascular lesion development. The purpose of this study was to examine whether smooth muscle cells (SMCs) inhibit EC secretion of ET-1. The effect of SMCs on EC ET-1 and constitutively expressed nitric oxide (NO) synthase activity was examined by using a bilayer co-culture model. SMCs inhibited both EC ET-1 protein and RNA levels, compared with ECs cultured alone. SMCs increased EC NO production when compared with ECs cultured alone. In addition, SMC inhibition of EC ET-1 production could be blocked by the NO synthase inhibitor N-G-Nitro-L arginine-methyl ester. ECs stimulated SMC proliferation, and the ET-1 AB and B receptor blockers inhibited EC stimulation of SMC proliferation. The ET-1 A blocker had no effect on SMC proliferation. We conclude that SMCs regulate EC ET-1 and ecNOS synthase transcript levels and protein levels. SMC inhibition of ET-1 production by ECs may be mediated through SMC-modulated changes in EC NO activity. Finally, EC stimulation of SMC proliferation in bilayer co-culture is mediated by ET-1 through the ET-1 B receptor.