Adipocytes promote nicotine-induced injury of endothelial cells via the NF-κB pathway

• Published in: Experimental cell research Vol. 359; no. 1; pp. 251 - 256
• Main Authors: Liu, Xiu, Wang, Chao-nan, Qiu, Chen-yang, Song, Wei, Wang, Lin-Fang, Liu, Bao
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2017
• Subjects: 3T3-L1 Cells; 60 APPLIED LIFE SCIENCES; Adipocytes; Adipocytes - drug effects; Adipocytes - metabolism; Adipocytes - pathology; ADIPOSE TISSUE; Animals; APOPTOSIS; Apoptosis - drug effects; Apoptosis - genetics; Cell Differentiation - drug effects; Co-culture; Coculture Techniques; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Endothelial Cells - pathology; EPITHELIUM; Human umbilical vein endothelial cells; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - metabolism; I-kappa B Kinase - metabolism; INJURIES; Mice; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; NF-κB pathway; NICOTINE; Nicotine - adverse effects; Proline - analogs & derivatives; Proline - pharmacology; Promoter Regions, Genetic - genetics; Proteolysis - drug effects; Signal Transduction - drug effects; Thiocarbamates - pharmacology; Up-Regulation - drug effects; Up-Regulation - genetics; PBS; MCP-1; Human umbilical vein endothelial cells; TNF-a; PDTC; NF-κB pathway; IKKβ; Adipocytes; IL-6; NF-κB; DMEM; FITC; IkBα; VECs; PI; PVAT; Co-culture; HUVECs; Nicotine; Apoptosis
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2017.07.022

Cigarette smoking is one of the most important risk factors of atherosclerosis, which can induce endothelial injury. Meanwhile, adipocytes are the main cell type of perivascular adipose tissue (PVAT), the largest endocrine and paracrine organ and direct anatomical connection to adventitia, which may play a key role in the injury of endothelial cells. We used nicotine to induce dysfunctional HUVECs and adipocytes. In addition, we used a novel model to co-culture HUVECs and adipocytes in vitro by the transwell co-culture system to determine the effect of adipocytes on endothelial injury. Cell apoptosis was detected by Annexin V-FITC. Genes and proteins involved in the nuclear factor kappa B (NF-κB) signaling pathway were detected by qRT-PCR and western blot analysis, respectively. We also investigated the nuclear translocation of NF-κB p65 using immunofluorescence staining. Our results showed that nicotine dose-dependently induces the apoptosis of HUVECs and adipocytes and is associated with increased IKKβ and NF-κB p65 expression and with IkBα degradation. Meanwhile through the co-culture system, adipocytes promoted the expression of IKKβ and NF-κB p65, as well as the translocation of NF-κB p65, and they accelerated the degradation of IkBα, resulting in increased apoptosis of HUVECs compared with that of the single cultured system. In conclusion, adipocytes could promote endothelial injury via the NF-κB pathway. Moreover, the NF-κB pathway plays pivotal roles in nicotine-induced vascular injury. [Display omitted] •Nicotine induces endothelial injury by activating NF-κB pathway.•Nicotine induces adipocytes injury by activating NF-κB pathway.•Adipocytes promote nicotine-induced endothelial injury via NF-κB pathway.