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

Abstract

Background-Data about the effects of smoking on thrombo-hemostatic factors (tissue factor [TF] and tissue factor pathway inhibitor ) 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 (Ϸ85%) 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 (PϽ0.02) and SP-stimulated (Pϭ0.059) t-PA production but similar basal and stimulated PAI-1 production (Pϭ0.9 and Pϭ0.6) compared with nonsmokers. Basal t-PA/PAI-1 molar ratio was significantly reduced in smokers (PϽ0.005). TFPI-1 level in the cell culture supernatant was also significantly lower in smokers compared with the nonsmoker group (PϽ0.05) with no difference in TF level between both groups (Pϭ0.5). As previously reported, both basal (PϽ0.001) and SP-stimulated (PϽ0.05) NO production were significantly reduced in smokers. Basal TFPI-1 in culture correlated positively with basal NO production (rϭ0.42, Pϭ0.04) and negatively with serum cotinine level (rϭϪ0.6, Pϭ0.01). 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.

Mechanisms of Coronary Thrombosis in Cigarette Smoke Exposure

“…67 In vitro, HUVECs exposed to serum from chronic smokers showed a relatively higher increase in TF level after 12 hours. 68 However, it was not statistically significant. 68 In the same cell culture supernatant, there was a significant decrease in EC-derived TFPI-1 secretion in the smoking group.…”

“…68 However, it was not statistically significant. 68 In the same cell culture supernatant, there was a significant decrease in EC-derived TFPI-1 secretion in the smoking group. .68 TFPI-1 is a potent regulator of TF factor VIIadependent activation of the TF pathway.…”

“…Additionally, TFPI-1 showed a significant positive correlation with NO. 68. This suggested that the prothrombotic alteration in TF/TFPI-1 could be partially mediated by decreased NO bioavailability.…”

“…The lysis of fibrin is mediated by plasmin. Plasminogen is activated to plasmin by t-PA. 68 On the contrary, t-PA is inhibited by PAI-1. 68 Smokers have higher PAI-1, which correlated with the estimated packyears of cigarettes smoked.…”

Cytochrome P450 Epoxygenase CYP2J2 G-50T Polymorphism is an Independent Genetic Prognostic Risk Factor and Interacts with Smoking Cessation After Index Premature Myocardial Infarction

“…Smoking can disturb lipoprotein metabolism by increasing insulin resistance and lipid intolerance, and is implicated in the production of small dense low-density lipoprotein (Craig et al, 1989;Eliasson et al, 1997;Barua et al, 2002). The smoking-associated risk of MI www.intechopen.com has been reported to be greater in subgrouping subjects with several genetic variants background Liu et al, 2005;Humphries et al, 2002).…”