Laboratory of Sex-Gender Medicine, National Institute of Biostructures and Biosystems Viale S. Antonio, Osilo, Italy ; Department of Biomedical Sciences, University of Sassari Via Muroni 23, Sassari, Italy.
Am J Transl Res. 2013 Aug 15;5(5):497-509. eCollection 2013.
Cigarette smoking (CS) is the primary cause of preventable morbidity and mortality. Abundant clinical evidence suggests that CS is more harmful to women; however, the mechanisms responsible for these differences are not yet known. CS alters endothelial function, the redox state, inflammation, and global DNA methylation, which is associated with one-carbon metabolism and the transsulfuration pathway. However, it is not known whether the previously identified alterations are sex-gender related. Healthy adult men and oral contraceptive-free women with regular menstrual cycles were enrolled; women were examined during the follicular phase. Men had higher plasma levels of uric acid, total bilirubin, homocysteine, glutamylcysteine, total glutathione, cysteinylglycine; had more monocytes and released more TNF-alpha from human monocytes derived macrophages (hMDMs), but they had fewer platelets and lower levels of DNA methylation, and their hMDMs released less TNF-alpha after LPS stimulation. MDA, taurine, cysteine, arginine, ADMA, and SDMA were not different. CS decreased global DNA methylation more in women and increased the platelet, monocyte, and lymphocyte counts and the homocysteine, arginine, and ADMA levels only in women, whereas increased the neutrophil and eosinophil counts only in men. Additionally, CS reduced the sex-gender differences in total bilirubin, basal and LPS-induced TNF-alpha release, total glutathione, and glutamylcysteine, leaving unchanged cysteinylglycine, taurine, SDMA, MDA, and cysteine. These data suggest that cardiovascular risk factors seem to come earlier in young healthy female smokers than in young healthy male smokers, supporting the greater alarmism regarding the effects of CS in women and providing a basis for understanding the sex-gender differences. These results also suggest that cessation programs targeting women are needed.
吸烟是可预防的发病率和死亡率的主要原因。大量临床证据表明，吸烟对女性的危害更大；然而，导致这些差异的机制尚不清楚。吸烟会改变内皮功能、氧化还原状态、炎症和全基因组 DNA 甲基化，这与一碳代谢和转硫途径有关。然而，目前还不清楚之前确定的改变是否与性别有关。本研究纳入了健康的成年男性和服用常规避孕药且月经周期规律的女性；女性在卵泡期进行检查。男性的血尿酸、总胆红素、同型半胱氨酸、谷氨酰半胱氨酸、总谷胱甘肽、半胱氨酸甘氨酸水平较高；有更多的单核细胞，从人单核细胞衍生的巨噬细胞（hMDMs）中释放更多的 TNF-α，但血小板较少，DNA 甲基化水平较低，其 hMDMs 在 LPS 刺激后释放的 TNF-α较少。MDA、牛磺酸、半胱氨酸、精氨酸、ADMA 和 SDMA 无差异。吸烟在女性中使全基因组 DNA 甲基化减少更多，仅在女性中增加血小板、单核细胞和淋巴细胞计数以及同型半胱氨酸、精氨酸和 ADMA 水平，而仅在男性中增加中性粒细胞和嗜酸性粒细胞计数。此外，吸烟减少了总胆红素、基础和 LPS 诱导的 TNF-α释放、总谷胱甘肽和谷氨酰半胱氨酸的性别差异，而对半胱氨酸甘氨酸、牛磺酸、SDMA、MDA 和半胱氨酸没有影响。这些数据表明，心血管危险因素似乎在年轻健康的女性吸烟者中比在年轻健康的男性吸烟者中更早出现，这支持了对女性吸烟危害的更大警惕，并为理解性别差异提供了依据。这些结果还表明，需要针对女性的戒烟计划。
