The Role of Sex in the Effects of Smoking and Nicotine in Cardiovascular Function, Atherosclerosis, and Inflammation.

IF 3 2区医学 Q2 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH Nicotine & Tobacco Research Pub Date : 2024-11-21 DOI:10.1093/ntr/ntae274

Ann Marie Centner, Abigail E Cullen, Leila Khalili, Vladimir Ukhanov, Stephanie Hill, Riley Deitado, Hyun Seok Hwang, Tooyib Azeez, Justin D La Favor, Orlando Laitano, Michelle S Parvatiyar, Stephen P Chelko, Gloria Salazar

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引用次数: 0

Abstract

Introduction: Cigarette smoke (CS) invokes an inflammatory response associated with vascular dysfunction and atherosclerosis. The role of sex and nicotine in CS effects on cardiovascular function and atherosclerosis is unexplored.

Methods: Male and female C57Bl/6 WT (wild type) and ApoE-/- mice were exposed to CS and nicotine with access to chow and water ad libitum for 16 weeks to fill this gap. Heart rate and endothelial function were measured in the aorta of WT mice, while the lipid profile, cytokines, chemokines, and plaque area and composition were assessed in ApoE-/- mice.

Results: CS increased heart rate similarly in both sexes and induced a more substantial impairment in endothelial function in males and more plaque in females than nicotine. Necrotic core areas were similar for both treatments in both sexes, while females had higher collagen deposition across treatments. Both treatments elevated senescence-associated GLB1/-galactosidase (SA-GLB1) and interleukin 17A (IL17A) similarly in both sexes. CS upregulated cholesterol in both sexes, triglycerides, VLDL, HDL, and C-X-C motif chemokine ligand-5 (CXCL5/LIX) only in males, and LDL and IL1A only in females. Additionally, nicotine metabolism showed sex-specific responses to nicotine but not smoking.

Conclusion: Findings suggest sex influences cardiovascular function and atherosclerosis following exposure to nicotine and CS.

Implications: The purpose of this study was to fill the existing literature gap through assessment of the differential sex effects of CS and nicotine on vascular function and atherosclerosis to identify sex-specific risk factors. We show sex-specific differences in endothelial function, plaque, inflammation, and extracellular matrix (ECM) regulators with exposure to CS and nicotine, which underscore the importance of assessing sex in tobacco and nicotine exposure studies. This study also shows the negative effect of oral nicotine administration as many oral dissolvable nicotine products, like pouches and gum, are becoming increasingly popular among adolescents and young adults.

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性别在吸烟和尼古丁对心血管功能、动脉粥样硬化和炎症的影响中的作用》（The Role of Sex in the Effects of Smoking and Nicotine in Cardiovascular Function, Atherosclerosis, and Inflammation）。

导言：香烟烟雾（CS）会引起与血管功能障碍和动脉粥样硬化相关的炎症反应。性别和尼古丁在 CS 对心血管功能和动脉粥样硬化的影响中的作用尚未得到研究：为了填补这一空白，研究人员将雄性和雌性 C57Bl/6 WT（野生型）小鼠和载脂蛋白E-/-小鼠暴露于 CS 和尼古丁中，并让它们自由进食和饮水 16 周。在 WT 小鼠的主动脉中测量了心率和内皮功能，而在 ApoE-/- 小鼠中评估了脂质概况、细胞因子、趋化因子以及斑块的面积和组成：结果：与尼古丁相比，CS对雄性和雌性小鼠心率的影响相似，但对雄性小鼠内皮功能的损害更大，对雌性小鼠斑块的影响更大。在两种处理中，雌雄动物的坏死核心区域相似，而雌性动物在各种处理中的胶原沉积更高。两种治疗方法都会使衰老相关的 GLB1/-半乳糖苷酶（SA-GLB1）和白细胞介素 17A（IL17A）升高。CS 在两性中都会上调胆固醇，在男性中会上调甘油三酯、VLDL、HDL 和 C-X-C motif 趋化因子配体-5（CXCL5/LIX），在女性中会上调低密度脂蛋白和 IL1A。此外，尼古丁代谢也显示出对尼古丁而非吸烟的性别特异性反应：结论：研究结果表明，暴露于尼古丁和CS后，性别会影响心血管功能和动脉粥样硬化：本研究的目的是通过评估CS和尼古丁对血管功能和动脉粥样硬化的不同性别影响来确定性别特异性风险因素，从而填补现有文献空白。我们发现，暴露于CS和尼古丁会导致血管内皮功能、斑块、炎症和细胞外基质（ECM）调节因子的性别差异，这强调了在烟草和尼古丁暴露研究中评估性别的重要性。这项研究还显示了口服尼古丁的负面影响，因为许多可溶解尼古丁口服产品，如小袋装和口香糖，在青少年和年轻人中越来越受欢迎。

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来源期刊

Nicotine & Tobacco Research 医学-公共卫生、环境卫生与职业卫生

CiteScore

8.10

自引率

10.60%

发文量

268

审稿时长

3-8 weeks

期刊介绍： Nicotine & Tobacco Research is one of the world''s few peer-reviewed journals devoted exclusively to the study of nicotine and tobacco. It aims to provide a forum for empirical findings, critical reviews, and conceptual papers on the many aspects of nicotine and tobacco, including research from the biobehavioral, neurobiological, molecular biologic, epidemiological, prevention, and treatment arenas. Along with manuscripts from each of the areas mentioned above, the editors encourage submissions that are integrative in nature and that cross traditional disciplinary boundaries. The journal is sponsored by the Society for Research on Nicotine and Tobacco (SRNT). It publishes twelve times a year.