TY - JOUR
T1 - Protein C pathway impairment in nonsymptomatic cigarette smokers
AU - Fernández, José A.
AU - Gruber, András
AU - Heeb, Mary Jo
AU - Griffin, John H.
N1 - Funding Information:
Correspondence and reprint requests to: José A. Fernández, M.D., PhD., Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road MEM-180, La Jolla, CA 92037. Telephone: (858) 784-2176. Fax: (858) 784-2243. E-mail: jfernand@scripps.edu. 1Grant support was provided by the Cigarette and Tobacco Surtax Fund of the State of California through the Tobacco-Related Disease Research Program of the University of California, Grant Nos. 1RT304 and 2RT0342, National Institutes of Health Grants HL52246 and MOI RR00833, and the Stein Endowment Fund. 2Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037. 3Department of BioMedical Engineering, Emory University, Atlanta, Georgia 30322.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
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U2 - 10.1006/bcmd.2002.0542
DO - 10.1006/bcmd.2002.0542
M3 - Article
C2 - 12482406
AN - SCOPUS:19044394521
SN - 1079-9796
VL - 29
SP - 73
EP - 82
JO - Blood cells, molecules & diseases
JF - Blood cells, molecules & diseases
IS - 1
ER -