Nicotine stimulates DNA synthesis and proliferation in vascular endothelial cells in vitro
Nicotine stimulates DNA synthesis and proliferation in vascular endothelial cells in vitro
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DOI：
10.1152/jappl.1998.84.6.2089
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发表时间：
1998-06-01
影响因子：
3.3
通讯作者：
Villablanca, AC
中科院分区：
文献类型：
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作者：
Villablanca, AC
尼古丁是香烟烟雾的主要成分，被认为在动脉粥样硬化和恶性肿瘤中起重要作用。内皮细胞的生长可能受到尼古丁的调控，但内皮水平的作用机制尚不清楚。通过培养牛肺动脉内皮细胞，研究了尼古丁(10（-14)-10(-4)M）对内皮细胞DNA合成、DNA修复、增殖和细胞毒性的影响。在有和没有羟基脲（一种DNA合成抑制剂）、血清、人血小板缺乏血浆、血小板衍生生长因子和内皮细胞生长因子（分别为PDGF和PDECGF）的情况下，用尼古丁孵育细胞进行检测。尼古丁对内皮细胞有明显刺激作用。DNA合成和增殖的浓度低于吸烟后血液中的浓度（< 10(-8)M）。血清（0.5%）和PDECGF增强尼古丁的刺激作用，并被尼古丁受体拮抗剂六甲溴铵阻断。对尼古丁的反应是双峰的，因为在较高浓度（bbb10 (-6) M）下观察到细胞毒性。这项研究对理解尼古丁作用的细胞机制具有启示意义。该结果可能对吸烟者的肿瘤血管生成、动脉粥样硬化和血管功能障碍具有重要意义。
Nicotine is a major component of cigarette smoke and has been postulated to play an important role in atherogenesis and malignancy. Endothelial cell growth may be regulated by nicotine, yet operative mechanisms at the endothelial level are poorly understood. We studied the effects of nicotine (10(-14)-10(-4) M) On endothelial DNA synthesis, DNA repair, proliferation, and cytotoxicity by using cultures of bovine pulmonary artery endothelial cells. Assays were performed on cells incubated with nicotine in the presence and absence of hydroxyurea (an inhibitor of scheduled DNA synthesis), serum, human platelet-poor plasma, and platelet-derived growth factor and endothelial cell growth factor (PDGF and PDECGF, respectively). Nicotine significantly stimulated endothelial cell. DNA synthesis and proliferation at concentrations lower than those obtained in blood after smoking (< 10(-8) M). The stimulatory effects of nicotine were enhanced by serum (0.5%) and PDECGF and were blocked by the nicotinic-receptor antagonist hexamethonium. The response to nicotine was bimodal because cytotoxicity was observed at higher concentrations (> 10(-6) M). This study has implications for understanding cellular mechanisms of nicotine action. The results may be important in tumor angiogenesis, atherogenesis, and vascular dysfunction in smokers.