title: Impaired capacity for acute endogenous fibrinolysis in smokers is restored by ascorbic acid.
abstract: Elevated levels of fibrinogen, C-reactive protein, and increased platelet aggregation are known to be increased by cigarette smoking, but the underlying mechanisms of the prothrombotic state in smokers are not completely understood. Since cigarette smoke contains several oxidants, we investigated the effect of the antioxidant ascorbic acid on stimulated fibrinolytic activity in smokers. Long-term heavy smokers and nonsmokers were studied by measurement of forearm blood flow; coinfusion of ascorbic acid was used to reduce oxidative stress. Concentrations of t-PA antigen and activity, of plasminogen activator inhibitor-1 (PAI-1) antigen and activity, and of C-reactive protein were determined by enzyme-linked immunosorbent assays and photometry, respectively. While dose-response curves of forearm blood flow elicited by substance P were not altered by the coadministration of ascorbic acid in nonsmokers, impaired flow in smokers markedly increased, P=0.003. Also, selectively in smokers, the maximal stimulated net release of t-PA antigen and of t-PA activity increased when ascorbic acid was infused simultaneously, P=0.002. In smokers CRP concentrations correlated significantly with the effect of ascorbic acid on maximal t-PA activity release, P<0.0001. Our data demonstrate that the endothelial capacity to acutely release t-PA is significantly reduced in heavy smokers and can be reversed by ascorbic acid. This association is particularly pronounced in smokers with high serum levels of C-reactive protein, suggesting that smoking-induced inflammation impairs fibrinolysis in these patients.
authors.affiliation: Department of Cardiology/Angiology, University Heart Center, University Hospital Hamburg, Martinistrasse 52, 20246 Hamburg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Kaehler
authors.forename: Katharina
authors.initials: K
authors.lastname: Koeke
authors.forename: Manuela
authors.initials: M
authors.lastname: Karstens
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schneppenheim
authors.forename: Thomas
authors.initials: T
authors.lastname: Meinertz
authors.forename: Thomas
authors.initials: T
authors.lastname: Heitzer
mesh_terms: D000328:Adult; D001205:Ascorbic Acid / Q000008:administration & dosage*; D002097:C-Reactive Protein / Q000032:analysis; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects; D012907:Smoking / Q000503:physiopathology*; D013373:Substance P / Q000008:administration & dosage; D010959:Tissue Plasminogen Activator / Q000097:blood / Q000378:metabolism
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D013373:Substance P; D002097:C-Reactive Protein; D010959:Tissue Plasminogen Activator; D001205:Ascorbic Acid