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(Circulation. 2002;106:905.)
© 2002 American Heart Association, Inc.

Brief Rapid Communications

Smoking Is Associated With Altered Endothelial-Derived Fibrinolytic and Antithrombotic Factors

An In Vitro Demonstration

Rajat S. Barua, MD; John A. Ambrose, MD; Dhanonjoy C. Saha, PhD; Lesley-Jane Eales-Reynolds, PhD

From Saint Vincent Catholic Medical Centers of New York (R.S.B., J.A.A., D.C.S.), New York, NY, and The School of Biomedical and Life Sciences (R.S.B., L.-J.R.), University of Surrey, UK.

Correspondence to John A. Ambrose, MD, The Comprehensive Cardiovascular Center, Department of Medicine, Saint Vincent Catholic Medical Centers of New York, 170 West 12th St, New York, NY 10011. E-mail jambrose{at}saintvincentsnyc.org

Background— Data about the effects of smoking on thrombo-hemostatic factors (tissue factor [TF] and tissue factor pathway inhibitor [TFPI-1]) are limited and on fibrinolytic factors (tissue plasminogen activator [t-PA] and plasminogen activator inhibitor-1 [PAI-1]) are debatable. The present study investigated the smoking-related, endothelial cell (EC)–specific responses for these factors and their relation to nitric oxide (NO) production in vitro.

Methods and Results— Serum from 8 nonsmokers and 15 smokers were incubated with confluent (85%) human umbilical vein endothelial cells (HUVECs) in 24-well tissue-culture plates for 12 hours. After the incubation, basal NO, t-PA, PAI-1, TF, TFPI-1 production, and substance P (SP)–stimulated NO, t-PA, and PAI-1 production were determined. HUVECs treated with smokers’ serum showed lower basal (P<0.02) and SP-stimulated (P=0.059) t-PA production but similar basal and stimulated PAI-1 production (P=0.9 and P=0.6) compared with nonsmokers. Basal t-PA/PAI-1 molar ratio was significantly reduced in smokers (P<0.005). TFPI-1 level in the cell culture supernatant was also significantly lower in smokers compared with the nonsmoker group (P<0.05) with no difference in TF level between both groups (P=0.5). As previously reported, both basal (P<0.001) and SP-stimulated (P<0.05) NO production were significantly reduced in smokers. Basal TFPI-1 in culture correlated positively with basal NO production (r=0.42, P=0.04) and negatively with serum cotinine level (r=-0.6, P=0.01).

Conclusions— These results indicate that cigarette smoking is associated with alterations in EC-derived fibrinolytic (t-PA) and antithrombotic (TFPI-1) factors. To our knowledge, this is the first demonstration that EC-derived TFPI is affected by smoking and endogenous NO or that the degree of smoke exposure may influence TFPI levels in an EC milieu.

Key Words: smoking • thrombosis • fibrinolysis • nitric oxide

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