Nicotine and cotinine up-regulate vascular endothelial growth factor expression in endothelial cells
Nicotine and cotinine up-regulate vascular endothelial growth factor expression in endothelial cells
复制标题
DOI：
10.1016/s0002-9440(10)64859-6
复制
发表时间：
2002-02-01
影响因子：
6
通讯作者：
Chen, CY
中科院分区：
文献类型：
--
作者：
Conklin, BS;Zhao, WD;Chen, CY
吸烟是血管疾病和各种癌症的重要危险因素。血管内皮生长因子（VEGF）是一种内皮特异性丝裂原，通常仅在正常动脉中低水平表达，但可能参与血管疾病和癌症的进展。一些临床证据表明，吸烟可能会增加血浆VEGF水平，但缺乏基础科学研究调查这种可能性。我们在这里显示，使用一个完整的猪颈总动脉灌注。培养模型中，尼古丁和尼古丁代谢主要产物可替宁引起内皮细胞VEGF表达显著增加。采用逆转录-聚合酶链反应比较各组间VEGF mRNA水平，而蛋白质水平的变化采用Western印迹和免疫组化证实。我们的研究结果显示，由于尼古丁和可替宁的浓度代表了习惯性吸烟者的血浆浓度，因此内皮细胞VEGF mRNA和蛋白水平显着增加。VEGF免疫染色也证实了这些结果。这些发现可能为吸烟引起的尼古丁和可替宁增加血管疾病进展以及肿瘤生长和转移的机制提供线索。
Cigarette smoking is an important risk factor for both vascular disease and various forms of cancer. Vascular endothelial growth factor (VEGF) is an endothelial-specific mitogen that is normally expressed only in low levels in normal arteries but may be involved in the progression of both vascular disease and cancer. Some clinical evidence suggests that cigarette smoking may increase plasma VEGF levels, but there is a lack of basic science studies investigating this possibility. We show here, using an intact porcine common carotid artery perfusion. culture model, that nicotine and cotinine, the major product of nicotine metabolism, cause a significant increase in endothelial cell VEGF expression. VEGF mRNA levels were compared between groups using reverse transcriptase-polymerase chain reaction, whereas protein level changes were demonstrated with Western blotting and immunohistochemistry. Our results showed significant increases in endothelial cell VEGF mRNA and protein levels because of nicotine and cotinine at concentrations representative of plasma concentrations seen in habitual smokers. VEGF immunostaining also paralleled these results. These findings may give a clue as to the mechanisms by which nicotine and cotinine from cigarette smoking increase vascular disease progression and tumor growth and metastasis.