Protein C pathway impairment in nonsymptomatic cigarette smokers
Protein C pathway impairment in nonsymptomatic cigarette smokers
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DOI：
10.1006/bcmd.2002.0542
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发表时间：
2002-07-01
影响因子：
2.3
通讯作者：
Griffin, JH
中科院分区：
文献类型：
--
作者：
Fernández, JA;Gruber, A;Griffin, JH
吸烟人群血栓形成风险的增加表明存在潜在的血栓前状态。众所周知，内皮细胞表面的氧化损伤发生在慢性吸烟者身上。蛋白C的活化主要发生在小血管的内皮上，而蛋白C的抗凝血活性需要易氧化的脂质膜的存在。我们的目的是分析吸烟与血浆中活化蛋白C、蛋白C酶原、活化蛋白C与蛇形蛋白复合物、总蛋白和游离蛋白S、c4b结合蛋白、凝血调节蛋白、纤维蛋白原、纤维蛋白肽A和蛋白酶裂解抗凝血酶III水平之间的关系。在本研究中使用的189名血浆捐献者中，83名无症状吸烟者（年龄范围20-44岁，男女比例= 1.13），106名健康非吸烟者（年龄范围22-59岁，男女比例= 1.36）。吸烟者的循环活化蛋白C比不吸烟者低23.3% (p = 0.003)，男性的差异比女性更明显。吸烟者的蛋白C水平也显著低于不吸烟者（p = 0.034）。吸烟强度与循环活化蛋白C水平呈负相关（r = -0.31, p = 0.004），吸烟与活化蛋白C与蛋白C酶原比值呈负相关（r == -0.37, p = 0.001）。吸烟强度与纤维蛋白原（r = 0.21, p = 0.042）、纤维蛋白肽A （r = 0.219, p = 0.034）呈正相关。测试的其他参数没有显示出吸烟数量的统计显著剂量反应。由于获得性活化蛋白C缺乏引起的香烟烟雾剂量依赖性高凝可能会增加吸烟者血栓形成的风险。(C) 2002 Elsevier Science （USA）。
Increased risk of thrombosis in cigarette smokers implies the existence of an underlying prethrombotic state. It is known that oxidative damage to the endothelium surface occurs in chronic smokers. Protein C activation takes place mostly on the endothelium of small vessels and the anticoagulant activity of protein C requires the presence of lipid membranes that are vulnerable to oxidation. Our objective was to analyze the relationship between smoking and plasma levels of activated protein C, protein C zymogen, activated protein C complexed with serpins, total and free protein S, C4b-binding protein, and thrombomodulin, as well as fibrinogen, fibrinopeptide A, and protease-cleaved antithrombin III. Of the 189 plasma donors used in this study 83 were nonsymptomatic smokers (age range 20-44 years, women/men ratio = 1.13) and 106 were healthy nonsmokers (age range 22-59 years, women/men ratio = 1.36). Smokers had 23.3% lower circulating activated protein C than nonsmokers (p = 0.003) and the differences were more pronounced in males than in females. Protein C levels were also significantly lower in smokers than in nonsmokers (p = 0.034). Correlations were negative between the intensity of smoking and circulating activated protein C levels (r = -0.31, p = 0.004) and between smoking and the ratio of activated protein C to protein C zymogen (r == -0.37, p = 0.001). Positive correlations were found between smoking intensity and fibrinogen (r = 0.21, p = 0.042), or fibrinopeptide A (r = 0.219, p = 0.034). Other parameters tested did not show a statistically significant dose-response for the number of cigarettes smoked. Cigarette smoke dose-dependent hypercoagulability due to acquired activated protein C deficiency could contribute to the increased risk of thrombosis in smokers. (C) 2002 Elsevier Science (USA).