NITRIC-OXIDE INHIBITION OF ENDOTHELIAL-CELL MITOGENESIS AND PROLIFERATION
NITRIC-OXIDE INHIBITION OF ENDOTHELIAL-CELL MITOGENESIS AND PROLIFERATION
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DOI：
10.1016/s0039-6060(05)80334-4
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发表时间：
1995-08-01
期刊：
影响因子：
3.8
通讯作者：
STANLEY, JC
中科院分区：
文献类型：
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作者：
SARKAR, R;WEBB, RC;STANLEY, JC
背景资料。血管壁损伤后，内皮细胞(EC)的增殖在血管修复中起着至关重要的作用。内皮细胞增殖受损可能是导致血管壁疾病的重要因素。一氧化氮(NO)抑制包括平滑肌细胞(SMC)在内的多种细胞的增殖。方法在体外培养的犬静脉内皮细胞中加入NO供体：S-N-亚硝基-N-乙酸乙酯、青霉胺(SNAP)、S-亚硝基-谷胱甘肽(GSNO)或NO精胺(SP-NO)。48小时后，根据细胞计数确定增殖茶。对大鼠主动脉SMC进行平行增殖实验。用NO供体二乙胺-NO(DEA-NO)处理S时相同步化的内皮细胞，通过掺入氚胸腺嘧啶核苷来测定细胞DNA合成。用NO拮抗剂cPTIO逆转DEA NO的作用。SNAP呈浓度依赖性抑制EC增殖(11%~71%；P<；0.05)。NO供体GSNO和SPNO以及SNAP对SMC的增殖抑制作用相似。DEA NO对ECDNA合成的抑制作用呈浓度依赖性(0.1~1 mm o l/L)(抑制率为39%~85%；p<；0.0 5)，该抑制作用可被cPTO逆转。NO抑制培养的内皮细胞的增殖和有丝分裂。这可能发生在某些病理状态，斑块和病变血管中NO的产生阻碍了再内皮化，从而导致不利的血栓和血管痉挛事件。
Background. Endothelial cell (EC) proliferation is essential in vascular repair after injury to the vessel wall. Impaired EC proliferation may be an important factor contributing to vessel wall disease. Nitric ic oxide (NO) inhibits proliferation of manqy cells, including smooth mucscle cells (SMC). We tested the hypothesis that NO inhibits EC proliferation and DAIA synthesis.Methods, Cultured canine venous ECs were treated with NO donors: S-n itroso-N-acet)lpenicillamine (SNAP), S-nitroso-glutathione (GSNO) or spermine NONOate (SP NO). Proliferation teas determined by cell counts after 48 hours. Parallel proliferation studies were done with rat aortic SMC. ECs synchronized in S phase were treated with the NO donor diethylamine NONOate (DEA NO), and DNA synthesis; was measured as the incorporation of tritiated thymidine. A NO antagonist, cPTIO, was used to reverse the effects of DEA NO.Results. Concentration-dependent (1 to 100 mmol/L) ingibition of EC proliferation (11% to 71% inhibition; p < 0.05) was seen with SNAP. Similar inhibition of proliferation was noted with the NO donors GSNO and SPNO and in SMC treated with SNAP. DEA NO caused concentration-dependent (0.1 to 1 mmol/L) inhibition of EC DNA synthesis (39% to 85% inhibition; p < 0.05), which was reversed by cPTIO.Conclusions. NO inhibits proliferation and mitogenesis of cultured ECs. This may occur in certain pathologic states, where production of NO in plaques and diseased vessels impedes reendothelialization, thus contributing to adverse thrombotic and vasospastic events.