Published Online
on August 5, 2002

A more recent version of this article appeared on August 20, 2002

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Submitted on June 5, 2002
Revised on June 26, 2002
Accepted on June 26, 2002

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, and 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.

^* To whom correspondence should be addressed. 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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