Endothelial Dysfunction, Impaired Endogenous Fibrinolysis, and Cigarette Smoking: A Mechanism for Arterial Thrombosis and Myocardial Infarction.
Newby, David E. BA, BSc, BM, MRCP; Wright, Robert A. MB, ChB, MRCP; Labinjoh, Catherine BSc, MB, ChB, MRCP; Ludlam, Christopher A. PhD, FRCP, FRCPath; Fox, Keith A.A. BSc, MB, ChB, FRCP, FESC; Boon, Nicholas A. MD, FRCP; Webb, David J. MD, FRCP, FRCPE, FFPM
[Article]
Circulation.
99(11):1411-1415, March 23, 1999.
(Format: HTML)
Background: Effective endogenous fibrinolysis requires rapid release of tissue plasminogen activator (tPA) from the vascular endothelium. Smoking is a known risk factor for arterial thrombosis and myocardial infarction, and it causes endothelial dysfunction. We therefore examined the effects of cigarette smoking on substance P-induced tPA release in vivo in humans.
Methods and Results-Blood flow and plasma fibrinolytic factors were measured in both forearms of 12 smokers and 12 age- and sex-matched nonsmokers who received unilateral brachial artery infusions of substance P (2 to 8 pmol/min). In both smokers and nonsmokers, substance P caused dose-dependent increases in blood flow and local release of plasma tPA antigen and activity (P<0.001 for all) but had no effect on the local release of plasminogen activator inhibitor type 1. Compared with nonsmokers, increases in forearm blood flow (P=0.03) and release of tPA antigen (P=0.04) and activity (P<0.001) caused by substance P were reduced in smokers. The area under the curve for release of tPA antigen and activity decreased by 51% and 53%, respectively.
Conclusions: Cigarette smoking causes marked inhibition of substance P-induced tPA release in vivo in humans. This provides an important mechanism whereby endothelial dysfunction may increase the risk of atherothrombosis through a reduction in the acute fibrinolytic capacity. (Circulation. 1999;99:1411-1415.)
(C) 1999 American Heart Association, Inc.
