American Heart Association-Tobacco Regulation and Addiction Center, Institute of Molecular Cardiology, and Diabetes and Obesity Center, University of Louisville, Louisville, KY.
Nicotine Tob Res. 2019 Jan 1;21(1):101-110. doi: 10.1093/ntr/ntx230.
Smokeless tobacco products such as snuff and snus are used worldwide. However, little is known about the systemic and cardiovascular toxicity of smokeless tobacco exposure.
Biomarkers of endothelial activation and injury, immune functions, platelet activation and insulin resistance were measured in 8-week old male C57BL/6 mice exposed to commercial snuff, CRP-2 reference snuff, commercial snus, CRP-1 reference snus, and nicotine in drinking water (100 µg/mL) for 4, 12, and 24 weeks.
Twenty-four weeks of exposure to smokeless tobacco products or nicotine significantly decreased the levels of circulating Flk+/Sca+ endothelial progenitor cells. Twelve and 24 weeks of exposure to all the smokeless tobacco products and nicotine significantly decreased the levels of circulating CD19+ B cells, CD4+ T cells, CD8+ T cells, and CD11b+ monocytes, whereas 4 weeks of exposure to Camel snus and Copenhagen snuff significantly depleted the levels of peripheral blood CD19+ B cells and CD11b+ monocytes. Twenty-four weeks of exposure to smokeless tobacco products or nicotine significantly decreased plasma IFNγ levels. However, plasma TNFα levels were significantly increased in mice exposed to Copenhagen snuff or nicotine for 24 weeks. This was accompanied by a five to sevenfold increase in the hepatic expression of TNFα. Neither smokeless products nor nicotine affected plasma lipoproteins, platelet activation, or systemic insulin sensitivity.
Chronic exposure to snuff and snus suppresses circulating levels of EPCs, endothelial microparticles and immune cells, but increases plasma TNF-α levels. These effects of smokeless tobacco products are attributable, at least in part, to nicotine.
Exposure to smokeless tobacco products results in the depletion of endothelial progenitor cells, which may impair the endothelium repair. Suppression of the circulating levels of immune cells upon exposure to smokeless tobacco products may increase the susceptibility to secondary infection. Increased formation of proinflammatory cytokines such as TNFα by nicotine or Copenhagen snuff may lead to vascular inflammation and thereby exacerbate atherogenesis.
鼻烟和鼻烟等无烟烟草制品在全球范围内被使用。然而，关于暴露于无烟烟草的系统和心血管毒性知之甚少。
在 8 周龄雄性 C57BL/6 小鼠中，测量内皮细胞激活和损伤、免疫功能、血小板激活和胰岛素抵抗的生物标志物，这些小鼠暴露于商业鼻烟、CRP-2 参考鼻烟、商业鼻烟、CRP-1 参考鼻烟和饮用水中的尼古丁（100μg/ml）4、12 和 24 周。
暴露于无烟烟草制品或尼古丁 24 周显著降低了循环 Flk+/Sca+内皮祖细胞的水平。12 周和 24 周暴露于所有无烟烟草制品和尼古丁显著降低了循环 CD19+B 细胞、CD4+T 细胞、CD8+T 细胞和 CD11b+单核细胞的水平，而 4 周暴露于骆驼鼻烟和哥本哈根鼻烟则显著耗尽外周血 CD19+B 细胞和 CD11b+单核细胞的水平。暴露于无烟烟草制品或尼古丁 24 周显著降低了血浆 IFNγ水平。然而，暴露于哥本哈根鼻烟或尼古丁 24 周的小鼠血浆 TNFα水平显著升高。这伴随着肝 TNFα表达增加五到七倍。无烟产品或尼古丁均不影响血浆脂蛋白、血小板激活或全身胰岛素敏感性。
慢性暴露于鼻烟和鼻烟会抑制循环中的 EPCs、内皮微泡和免疫细胞水平，但会增加血浆 TNF-α水平。这些无烟烟草制品的作用至少部分归因于尼古丁。
暴露于无烟烟草制品会导致内皮祖细胞耗竭，这可能会损害内皮修复。暴露于无烟烟草制品后循环免疫细胞水平下降可能会增加继发感染的易感性。尼古丁或哥本哈根鼻烟引起的促炎细胞因子（如 TNFα）的形成增加可能导致血管炎症，从而加剧动脉粥样硬化的发生。
