title: Benzo[a]pyrene induces oxidative stress and endothelial progenitor cell dysfunction via the activation of the NF-κB pathway.
abstract: Smoking is a major risk factor for atherosclerosis. In this study, we evaluated the effects of benzo[a]pyrene (BaP, a prominent component of tobacco smoke) on the function and pro-inflammatory response of human endothelial progenitor cells (EPCs). EPCs were isolated from umbilical cord blood and treated with different concentrations (10, 20 and 50 µmol/l) of BaP. The proliferation, migration, adhesion and angiogenesis of BaP-treated EPCs were evaluated using the cell counting kit-8 (CCK-8), Transwell assay, adhesion assay and in vitro tube formation assay, respectively. The activation of nuclear factor-κB (NF-κB) was evaluated by measuring the mRNA expression of NF-κB p65 and p50 by real-time RT-PCR and NF-κB translocation assay. Reactive oxygen species (ROS) production was determined by the reduction of fluorescent 2',7'-dichlorofluorescein diacetate (DCFH-DA). The results demonstrated that BaP treatment significantly inhibited the proliferation, migration, adhesion and angiogenesis of EPCs in vitro. In addition, BaP induced the release of interleukin (IL)-1β and tumor necrosis factor-α from these cells. Moreover, the exposure of EPCs to BaP induced ROS generation and the activation of NF-κB. Experiments with EPCs pre-treated with pyrrolidine dithiocarbamate, an inhibitor of NF-κB, revealed that the BaP-mediated inhibition of proliferation, migration, adhesion and angiogenesis of EPCs is mainly regulated by NF-κB. Thus, tobacco smoke may induce oxidant-mediated stress responses in EPCs and impair their function via the activation of the NF-κB pathway.
authors: Department of Cardiology, The Second Affiliated Hospital, Wenzhou Medical College, Wenzhou, Zhejiang, PR China.
authors: Kangting
authors: K
authors: Ji
authors: Cheng
authors: C
authors: Xing
authors: Fengchun
authors: F
authors: Jiang
authors: Xiaoyan
authors: X
authors: Wang
authors: Huihui
authors: H
authors: Guo
authors: Jinliang
authors: J
authors: Nan
authors: Lu
authors: L
authors: Qian
authors: Penglin
authors: P
authors: Yang
authors: Jiafeng
authors: J
authors: Lin
authors: Meide
authors: M
authors: Li
authors: Jinnong
authors: J
authors: Li
authors: Lianming
authors: L
authors: Liao
authors: Jifei
authors: J
authors: Tang
mesh_terms: D000704:Analysis of Variance; D001564:Benzo(a)pyrene / Q000633:toxicity*; D002468:Cell Physiological Phenomena / Q000187:drug effects; D002478:Cells, Cultured; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D018384:Oxidative Stress / Q000187:drug effects*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D001564:Benzo(a)pyrene