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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:712.)
© 2009 American Heart Association, Inc.

Cell Biology/Signaling

Effects of Aspirin on Clot Structure and Fibrinolysis Using a Novel In Vitro Cellular System

R.A. Ajjan; K.F. Standeven; M. Khanbhai; F. Phoenix; K.C. Gersh; J.W. Weisel; M.T. Kearney; R.A.S. Ariëns; P.J. Grant

From the Division of Cardiovascular and Diabetes Research (R.A.A., K.F.S., M.K., F.P., M.T.K., R.A.S.A., P.J.G.), Leeds Institute for Genetics, Health, and Therapeutics (LIGHT), University of Leeds, UK; and the Department of Cell and Developmental Biology (K.C.G., J.W.W.), University of Pennsylvania School of Medicine, Philadelphia.

Correspondence to Peter J. Grant, MD, FRCP, Division of Cardiovascular and Diabetes Research, The LIGHT Laboratories, University of Leeds, Leeds, LS2 9JT, United Kingdom. E-mail p.j.grant{at}leeds.ac.uk

Objectives— The purpose of this study was to investigate the direct effects of aspirin on fibrin structure/function.

Methods and Results— Chinese Hamster Ovary cell lines stably transfected with fibrinogen were grown in the absence (0) and presence of increasing concentrations of aspirin. Fibrinogen was purified from the media using affinity chromatography, and clots were made from recombinant protein. Mean final turbidity [OD(±SEM)] was 0.083(±0.03), 0.093(±0.002), 0.101(±0.005), and 0.125(±0.003) in clots made from 0, 1, 10, and 100 mg/L aspirin-treated fibrinogen, respectively (P<0.05). Permeability coefficient (Ks cm²x10^–8) was 1.68(±0.29) and 4.13(±0.33) comparing fibrinogen produced from cells grown with 0 mg/L and 100 mg/L aspirin respectively (P<0.05). Scanning electron microscopy confirmed a looser clot structure and increased fiber thickness of clots made from aspirin-treated fibrinogen, whereas rheometer studies showed a significant 30% reduction in clot rigidity. Fibrinolysis was quicker in clots made from aspirin-treated fibrinogen. Ex vivo studies in 3 normal volunteers given 150 mg aspirin daily for 1 week demonstrated similar changes in clot structure/function.

Conclusion— Aspirin directly altered clot structure resulting in the formation of clots with thicker fibers and bigger pores, which are easier to lyse. This study clearly demonstrates an alternative mode of action for aspirin, which should be considered in studies evaluating the biochemical efficacy of this agent.

We investigated the direct effects of aspirin on fibrin clot structure and fibrinolysis both in vitro and ex vivo. We showed that aspirin mainly acetylates the alpha chain of fibrinogen, resulting in the formation of clots with thicker fibers, larger pores, and reduced rigidity, which are easier to lyse.

Key Words: —fibrinogen • aspirin • fibrin polymerization • fibrin structure • acetylation • fibrinolysis

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