Smoking is associated with altered endothelial-derived fibrinolytic and antithrombotic factors: an in vitro demonstration.
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.


RESULTS
Serum from 8 nonsmokers and 15 smokers were incubated with confluent (approximately 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.
Barua
Rajat S
RS
Saint Vincent Catholic Medical Centers of New York, New York, NY 10011, USA.
Ambrose
John A
JA
Saha
Dhanonjoy C
DC
Eales-Reynolds
Lesley-Jane
LJ
D000328:Adult; D002478:Cells, Cultured; D003367:Cotinine / Q000097:blood; D016757:Death, Sudden, Cardiac / Q000209:etiology; D004730:Endothelium, Vascular / Q000378:metabolism*; D005343:Fibrinolytic Agents / Q000378:metabolism*; D006801:Humans; D008074:Lipoproteins / Q000096:biosynthesis; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology; D009569:Nitric Oxide / Q000096:biosynthesis; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis; D012907:Smoking / Q000009:adverse effects; D013925:Thromboplastin / Q000096:biosynthesis; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis
D005343:Fibrinolytic Agents; D008074:Lipoproteins; D017395:Plasminogen Activator Inhibitor 1; C051928:lipoprotein-associated coagulation inhibitor; D009569:Nitric Oxide; D013925:Thromboplastin; D010959:Tissue Plasminogen Activator; D003367:Cotinine