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.
Saint Vincent Catholic Medical Centers of New York, New York, NY 10011, USA.
Rajat S
RS
Barua
John A
JA
Ambrose
Dhanonjoy C
DC
Saha
Lesley-Jane
LJ
Eales-Reynolds
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