title: Nicotine and cotinine up-regulate vascular endothelial growth factor expression in endothelial cells.
abstract: 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.
authors.affiliation: Department of Surgery, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Conklin
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhao
authors.forename: Dian-Sheng
authors.initials: DS
authors.lastname: Zhong
authors.forename: Changyi
authors.initials: C
authors.lastname: Chen
mesh_terms: D000818:Animals; D003367:Cotinine / Q000494:pharmacology*; D046508:Culture Techniques; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D010477:Perfusion; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012907:Smoking / Q000009:adverse effects; D013552:Swine; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D008222:Lymphokines; D018722:Nicotinic Agonists; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D009538:Nicotine; D003367:Cotinine