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

Barua, Rajat S., Ambrose, John A., Saha, Dhanonjoy C. and Eales-Reynolds, Lesley-Jane ORCID: (2002) Smoking is associated with altered endothelial-derived fibrinolytic and antithrombotic factors: an in vitro demonstration. Circulation, 106 (8). pp. 905-908. ISSN 0009-7322

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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 (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{\textless}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{\textless}0.005). TFPI-1 level in the cell culture supernatant was also significantly lower in smokers compared with the nonsmoker group (P{\textless}0.05) with no difference in TF level between both groups (P=0.5). As previously reported, both basal (P{\textless}0.001) and SP-stimulated (P{\textless}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.

Item Type: Article
Identifier: 10.1161/01.CIR.0000029091.61707.6B
Keywords: Male, Humans, Cells, Cultured, Adult, Nitric Oxide, Cotinine, Endothelium, Vascular, Smoking, Death, Sudden, Cardiac, Fibrinolytic Agents, Lipoproteins, Myocardial Infarction, Plasminogen Activator Inhibitor 1, Thromboplastin, Tissue Plasminogen Activator
Subjects: Medicine and health > Clinical medicine
Medicine and health
Depositing User: Lesley-Jane Eales-Reynolds
Date Deposited: 20 May 2018 06:54
Last Modified: 06 Feb 2024 15:57

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