Helmersson J, Larsson A, Vessby B, Basu S
Sections of Geriatrics and Clinical Nutrition Research, Department of Public Health and Caring Sciences, Uppsala University, Sweden.
Atherosclerosis. 2005 Jul;181(1):201-7. doi: 10.1016/j.atherosclerosis.2004.11.026. Epub 2005 Apr 26.
The underlying mechanisms by which smoking induces cardiovascular diseases are largely unknown. The effect of smoking status on the cyclooxygenase (COX)-mediated inflammatory indicator prostaglandin F(2alpha) (PGF(2alpha)) has never been studied. Associations of cytokines and antioxidants and smoking status, have shown conflicting results. Urinary 15-keto-dihydro-PGF(2alpha) (a major metabolite of PGF(2alpha)), serum interleukin-6 (IL-6) and high sensitivity C-reactive protein (hsCRP), serum amyloid protein A (SAA), urinary 8-iso-PGF(2alpha) (an F(2)-isoprostane, indicator of oxidative stress), and serum alpha-tocopherol were quantified in a population-based sample (n = 642) of 77-year old men without diabetes. Fifty-five men were current smokers and 391 former smokers. Inflammatory indicators were increased in current smokers (15-keto-dihydro-PGF(2alpha), P < 0.001; IL-6, P = 0.01) than non-smokers. 8-iso-PGF(2alpha) was increased (P < 0.01) and alpha-tocopherol reduced (P < 0.001) in current smokers. Further, former smokers had increased formation of 15-keto-dihydro-PGF(2alpha), IL-6 and 8-iso-PGF(2alpha) compared non-smokers. This is the first study to show that smokers have increased PGF(2alpha) formation, thus enhanced COX-mediated inflammation, in addition to elevated levels of cytokines and isoprostanes. Subclinical COX- and cytokine-mediated inflammation and oxidative stress are ongoing processes not only in active smokers but also in former smokers which may contribute to the accelerated atherosclerosis associated with smoking.
吸烟诱发心血管疾病的潜在机制在很大程度上尚不清楚。吸烟状态对环氧化酶（COX）介导的炎症指标前列腺素F（2α）（PGF（2α））的影响从未被研究过。细胞因子、抗氧化剂与吸烟状态之间的关联结果相互矛盾。在一个基于人群的77岁无糖尿病男性样本（n = 642）中，对尿15 - 酮 - 二氢 - PGF（2α）（PGF（2α）的主要代谢产物）、血清白细胞介素 - 6（IL - 6）和高敏C反应蛋白（hsCRP）、血清淀粉样蛋白A（SAA）、尿8 - 异 - PGF（2α）（一种F（2） - 异前列腺素，氧化应激指标）以及血清α - 生育酚进行了定量分析。其中55名男性为当前吸烟者，391名男性为既往吸烟者。与非吸烟者相比，当前吸烟者的炎症指标升高（15 - 酮 - 二氢 - PGF（2α），P < 0.001；IL - 6，P = 0.01）。当前吸烟者的8 - 异 - PGF（2α）升高（P < 0.01），α - 生育酚降低（P < 0.001）。此外，与非吸烟者相比，既往吸烟者的15 - 酮 - 二氢 - PGF（2α）、IL - 6和8 - 异 - PGF（2α）生成增加。这是第一项表明吸烟者除了细胞因子和异前列腺素水平升高外，PGF（2α）生成增加，从而增强COX介导的炎症的研究。亚临床COX和细胞因子介导的炎症以及氧化应激不仅在现吸烟者中，而且在既往吸烟者中都是持续存在的过程，这可能导致与吸烟相关的动脉粥样硬化加速。
