Nicotine exposure alters human vascular smooth muscle cell phenotype from a contractile to a synthetic type
Nicotine exposure alters human vascular smooth muscle cell phenotype from a contractile to a synthetic type
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DOI：
10.1016/j.atherosclerosis.2014.10.019
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发表时间：
2014-12-01
期刊：
影响因子：
5.3
通讯作者：
Nakamura, Akio
中科院分区：
文献类型：
--
作者：
Yoshiyama, Shinji;Chen, Zhenyi;Nakamura, Akio
目的：吸烟是已知的动脉硬化的危险因素。在动脉粥样硬化斑块中，血管平滑肌细胞（VSMCs）表现出不同于正常条件下收缩型的表型。尼古丁是香烟烟雾中的主要药理剂。然而，尼古丁对VSMC的任何直接影响仍然不确定。由于尼古丁促进VSMC迁移，其表型可能因尼古丁而改变。方法和结果：我们使用人主动脉原代平滑肌细胞（HuAoSMCs），用转化生长因子-β分化，研究暴露于0.1 μ M尼古丁48 h后分化标志物的蛋白水平和促分裂原活化蛋白激酶（MAPK）活性的变化。尼古丁暴露后，合成型标记物肌球蛋白II 10（2.93倍）和β-肌动蛋白（1.66倍）的蛋白水平增加。与此相反，收缩型标记物，肌球蛋白II 11（0.63倍），高分子量钙调蛋白（0.40倍）和SM 22（0.66倍），这涉及分化的VSMC的水平下降。此外，尼古丁暴露诱导p38 MAPK（1.30倍）和细胞外信号调节激酶（1.91倍）的激活增强。这些结果表明，由于尼古丁暴露，HuAoSMCs的表型已经改变为合成样类型。因此，尼古丁是可以改变VSMC中分化标志物的蛋白质表达的一个因素。此外，细胞内Ca ~（2+）水平的增加表明，尼古丁的这些作用是通过烟碱乙酰胆碱受体介导的。结论：尼古丁可促进血管平滑肌细胞从图尼卡中膜向血管内膜粥样斑块迁移。这可能是由于尼古丁通过烟碱乙酰胆碱受体和G蛋白偶联受体直接诱导VSMC由收缩型向合成样型转化。(C)2014爱思唯尔爱尔兰有限公司版权所有。
Objective: Cigarette smoking is a known risk factor for arteriosclerosis. In atheromatous plaques, vascular smooth muscle cells (VSMCs) display a phenotype that is different from the contractile type under normal conditions. Nicotine is the major pharmacological agent in cigarette smoke. However, any direct effect of nicotine on VSMCs remains uncertain. Because nicotine promotes VSMC migration, its phenotype may change due to nicotine. Approach and results: We used human aorta primary smooth muscle cells (HuAoSMCs), differentiated with transforming growth factor-beta, to investigate changes in the protein levels of differentiation markers and in the activity of mitogen-activated protein kinases (MAPKs) after exposure to 0.1 mu M of nicotine for 48 h. After nicotine exposure, the protein levels of myosin II 10 (2.93-fold) and beta-actin (1.66-fold), synthetic type markers, were increased. In contrast, the levels of the contractile type markers, myosin II 11 (0.63-fold), high-molecular-weight caldesmon (0.40-fold) and SM22 (0.66-fold), which concern differentiated VSMC, were decreased. Moreover, nicotine exposure induced enhanced activation of p38 MAPK (1.30-fold) and extracellular signal-regulated kinase (1.91-fold). These results indicated that the phenotype of HuAoSMCs had changed to a synthetic-like type because of nicotine exposure. Thus, nicotine is one factor that can alter protein expression of differentiation markers in VSMCs. Besides, the increase of intracellular Ca2+ levels suggested that these effects of nicotine were mediated through nicotinic acetylcholine receptors. Conclusion: Nicotine has already been reported to promote VSMC migration from the tunica media to atheromatous plaques in the vascular intima. This phenomenon may occur because nicotine directly induces VSMC transformation from contractile type to synthetic-like type via nicotinic acetylcholine receptors and G protein-coupled receptors. (C) 2014 Elsevier Ireland Ltd. All rights reserved.