Nicotine-induced vascular endothelial growth factor release via the EGFR-ERK pathway in rat vascular smooth muscle cells
Nicotine-induced vascular endothelial growth factor release via the EGFR-ERK pathway in rat vascular smooth muscle cells
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DOI：
10.1016/j.lfs.2006.12.033
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发表时间：
2007-03-20
期刊：
影响因子：
6.1
通讯作者：
Watanabe, Yasuhiro
中科院分区：
文献类型：
--
作者：
Kanda, Yasunari;Watanabe, Yasuhiro
香烟烟雾已被确定为动脉粥样硬化和其他血管疾病的独立危险因素。生长因子诱导的血管平滑肌细胞（VSMC）的增殖和迁移被认为在动脉粥样硬化的进展中发挥重要作用。在本研究中，我们研究了尼古丁（香烟烟雾的重要成分之一）对大鼠 VSMC 血管内皮生长因子 (VEGF) 释放的影响。用尼古丁刺激细胞导致 VEGF 的时间和浓度依赖性释放。 Hexamethium 是烟碱乙酰胆碱受体 (nAChR) 的拮抗剂，可抑制尼古丁诱导的 VEGF 释放。接下来我们研究了尼古丁诱导细胞中 VEGF 释放的机制。 U0126（MEK 的选择性抑制剂）治疗可抑制尼古丁诱导的 VEGF 释放，从而减弱尼古丁诱导的 ERK 磷酸化。尼古丁诱导 ERK 短暂磷酸化。此外，AG1478 是一种选择性表皮生长因子受体 (EGFR) 激酶抑制剂，可抑制尼古丁诱导的 ERK 磷酸化和 VEGF 释放。这些数据表明尼古丁通过 VSMC 中的 nAChR 释放 VEGF。此外，尼古丁诱导的 VEGF 释放是由 VSMC 中的 EGFR-ERK 通路介导的。 VEGF 可能会增加吸烟者患心血管疾病的风险。 (c) 2007 Elsevier Inc. 保留所有权利。
Cigarette smoke has been firmly established as an independent risk factor for atherosclerosis and other vascular diseases. The proliferation and migration of vascular smooth muscle cells (VSMC) induced by growth factors have been proposed to play an important role in the progression of atherosclerosis. In the present study, we investigated the effects of nicotine, which is one of the important constituents of cigarette smoke, on vascular endothelial growth factor (VEGF) release, in rat VSMC. The stimulation of cells with nicotine resulted in a time- and concentration-dependent release of VEGF. Hexamethonium, an antagonist of nicotinic acetylcholine receptor (nAChR), inhibited nicotine-induced VEGF release. We next investigated the mechanisms by which nicotine induces VEGF release in the cells. The nicotine-induced VEGF release was inhibited by treatment with U0126, a selective inhibitor of MEK, which attenuated the nicotine-induced ERK phosphorylation. Nicotine induced a transient phosphorylation of ERK. Furthermore, AG1478, a selective inhibitor of epidermal growth factor receptor (EGFR) kinase, inhibited nicotine-induced ERK phosphorylation and VEGF release. These data suggest that nicotine releases VEGF through nAChR in VSMC. Moreover, VEGF release induced by nicotine is mediated by an EGFR-ERK pathway in VSMC. VEGF may contribute to the risk of cardiovascular diseases in cigarette smokers. (c) 2007 Elsevier Inc. All rights reserved.