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Protein C pathway impairment in nonsymptomatic cigarette smokers

Academic Article
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Overview

authors

  • Fernandez, J. A.
  • Gruber, A.
  • Heeb, Mary Jo
  • Griffin, John

publication date

  • July 2002

journal

  • Blood Cells Molecules and Diseases  Journal

abstract

  • 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.

subject areas

  • Adult
  • Complement Inactivator Proteins
  • Female
  • Fibrinogen
  • Fibrinopeptide A
  • Glycoproteins
  • Humans
  • Male
  • Middle Aged
  • Protein C
  • Serpins
  • Smoking
  • Thrombomodulin
  • Thrombophilia
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Research

keywords

  • activated protein C
  • coagulation
  • protein S
  • smoking
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Identity

International Standard Serial Number (ISSN)

  • 1079-9796

Digital Object Identifier (DOI)

  • 10.1006/bcmd.2002.0542

PubMed ID

  • 12482406
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Additional Document Info

start page

  • 73

end page

  • 82

volume

  • 29

issue

  • 1

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