Protein C pathway impairment in nonsymptomatic cigarette smokers.
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.
Fernández
José A
JA
Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road MEM-180, La Jolla, CA 92037, USA. jfernand@scripps.edu
Gruber
András
A
Heeb
Mary Jo
MJ
Griffin
John H
JH
D000328:Adult; D003169:Complement Inactivator Proteins / Q000032:analysis; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D005344:Fibrinopeptide A / Q000032:analysis; D006023:Glycoproteins; D006801:Humans; D008297:Male; D008875:Middle Aged; D011486:Protein C / Q000032:analysis / Q000378:metabolism*; D015843:Serpins / Q000097:blood; D012907:Smoking / Q000009:adverse effects / Q000097:blood*; D018180:Thrombomodulin / Q000097:blood; D019851:Thrombophilia / Q000209:etiology*
D003169:Complement Inactivator Proteins; D006023:Glycoproteins; D011486:Protein C; D015843:Serpins; D018180:Thrombomodulin; D005344:Fibrinopeptide A; D005340:Fibrinogen