NF-κB pathway mediates vascular smooth muscle response to nicotine

• Published in: The international journal of biochemistry & cell biology 2013-02, Vol.45 (2), p.375-383
• Main Authors: Wang, Zhaoxia, Wu, Weidong, Tang, Maoping, Zhou, Ying, Wang, Lianyun, Xu, Wangjie, Qiao, Zhongdong
• Format: Article
• Language: English
• Subjects: Bungarotoxins - pharmacology; Cardiovascular disease; cardiovascular diseases; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cell Movement; Cell Nucleus - metabolism; Cells, Cultured; coculture; Coculture Techniques; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - metabolism; cytoskeleton; endothelial cells; flow cytometry; Gene Expression - drug effects; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - metabolism; Humans; I-kappa B Kinase - metabolism; I-kappa B Proteins - metabolism; Migration; Muscle, Smooth, Vascular - cytology; myocytes; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; NF-kappa B - metabolism; NF-κB signaling pathway; Nicotine; Nicotine - pharmacology; Nicotinic Agonists - pharmacology; Nicotinic Antagonists - pharmacology; Phosphorylation; Protein Processing, Post-Translational; protein synthesis; Protein Transport - drug effects; Signal Transduction; smooth muscle; transcription factor NF-kappa B; Umbilical Veins - cytology; Vascular smooth muscle cell
• ISSN: 1357-2725; 1878-5875
• DOI: 10.1016/j.biocel.2012.10.016

Vascular smooth muscle cells (SMCs) and endothelial cells (ECs) play important roles in nicotine-induced cardiovascular disease. To elucidate the mechanism underlying the abnormal SMC behavioral response to nicotine, we investigated the activation of the NF-κB signal transduction pathway and cell adhesion molecular (CAM) expression on SMCs. Also we used different cell culture manner of SMC sole and EC–SMC co-culture with a 0.4 or a 3μm membrane pore, to observe whether there is a crosstalk between EC/SMC involved in the process of NF-κB pathway activation. Nicotine-induced effects were observed in SMCs by both monoculture and co-culture with the 3μm-pore size, including the phosphorylation of IKK and IκB, the shift of transcription factor NF-κB, and the enhancement of SMC cytoskeleton protein expression and migration ability, but none were observed by co-culture with the 0.4μm-pore size. All of the actions could be distinctly blocked by α-bungarotoxin (α7 nicotinic receptor inhibitor) or PDTC (NF-κB suppressor). Flow cytometry analysis showed that the adhesion molecules ICAM-1 and LFA-1 and VCAM-1 and VLA-4 were better expressed similarly on the surface of SMCs in the monoculture and 3μm-pore size co-culture system vs. the 0.4μm co-culture way. The results imply that nicotine induces SMC cytoskeleton protein up-expression and migration via the NF-κB signaling pathway and that EC–SMC crosstalk via CAM facilitates its response to nicotine.