Abstract
Fibrin is a major component of atherosclerotic plaques, and there may also be situations in which intravascular fibrin is formed in contact with the endothelium. The studies to be presented describe the distribution of fibrinogen/fibrin I, fibrin II, and fragments D and D-dimer in normal vessels and atherosclerotic plaques of increasing severity and also describe some functional effects of fibrin on normal endothelium. Immunohistochemical studies using three specific monoclonal antibodies with the avidin-biotin complex immunoperoxidase technique demonstrated that little fibrinogen/fibrin I or fibrin II and no D/D-dimer were detected in normal aortas. In early lesions and in fibrous plaques, fibrinogen/fibrin I and fibrin II were distributed in long threads and around vessel wall cells. D/D-dimer was not seen in early lesions. In advanced plaques all three molecular forms were detected in areas of loose connective tissue, in thrombi, and around cholesterol crystals. Thus increased fibrin formation and degradation may be associated with progression of atherosclerotic disease. Additionally, the presence of fibrin II around vessel wall cells suggests that these cells may be involved in the fbgn to fibrin transition within the vessel wall.
The second aspect of the work to be presented concerns effects of fibrin on vascular endothelium. Fibrin formed on the surface of cultured human umbilical vein endothelial cells stimulated production of prostacyclin and tissue plasminogen activator by the cells in a time-and dose-dependent manner. Stimulation of prostacyclin was completely inhibited by indomethacin and partially inhibited by actinomycin D, cycloheximide, and trifluoperazine, while stimulation of t-PA synthesis was completely inhibited by actinomycin D and cycloheximide and partially inhibited by cytochalasin D, vinblastine, and trifluoperazine Neither collagen polymerization on the cells nor thrombin added in subclotting concentrations was stimulatory, and Reptilase fibrin caused only a slight increase in t-PA. Soluble fibrin II generated in the presence of gly-pro-arg-pro failed to stimulate production of prostacyclin or t-PA. Thus these studies demonstrate that polymerized fibrin II is necessary for stimulation. Such stimulation could limit vascular occlusion by inhibiting platelet activation and stimulating fibrinolysis via tissue plasminogen activator.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
R. Ross, J. Glomset, and L. Harker. A platelet-dependent serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro. Proc. Natl. Acad. Sci. USA,71:1207–1210, (1974).
C. V. Rokitansky. A manual of pathologic anatomy. The Syndenham Society, London, 4.265–275, (1852).
F. W. Beneke. Grundlinien der Pathologie des Stoffwechsels. Berlin, (1874).
F. B. Mallory. The Infectious Lesions of Blood Vessels, in: The Harvey Lectures, New York (1912), pp. 150–166.
E. Clark, I. Graef, and H. Chasis. Thrombosis of the aorta and coronary arteries. Arch. Pathol, 22:183–212, (1936).
J. B. Duguid. Thrombosis as a factor in the pathogenesis of aortic atherosclerosis. J. Pathol. Bacteriol, 60:57–61, (1948).
A. Bini, J. J. Fenoglio, Jr., J. Sobel, J. Owen, M. Fejgl, and K. L. Kaplan. Immunochemical characterization of fibrinogen, fibrin I and fibrin II in human thrombi and atherosclerotic lesions. Blood, 69:1038–1045 (1987).
A. Bini, J. J. Fenoglio, Jr., R. Mesa-Tejada, B. Kudryk, and K. L. Kaplan. Identification and distribution of fibrinogen, fibrin, and fibrin(ogen) degradation products in atherosclerosis. Use of monoclonal antibodies. Arteriosclerosis,9:109–121 (1989).
A. Bini, R. Mesa-Tejada, J. J. Fenoglio, Jr., B. Kudryk, and K. L. Kaplan. Immunohistochemical characterization of fibrin(ogen)-related antigens in human tissues using monoclonal antibodies. Lab. Invest, 60:814–821, (1989).
K. L. Kaplan, T, Mather, L. DeMarco, and S. Solomon. Effect of fibrin on endothelial cell production of prostacyclin and tissue plasminogen activator. Arteriosclerosis,9:43–49, (1989).
J. L. Kadish, C. E. Butterfield, and J. Folkman. The effect of fibrin on cultured vascular endothelial cells. Tissue Cell, 11:99–108(1979).
K. Watanabe and K. Tanaka. Influence of fibrin, fibrinogen and fibrinogen degradation products on cultured endothelial cells. Atherosclerosis, 48:57–70, (1983).
R. R. Schleef and C. R. Birdwell. The effect of fibrin on endothelial cell migration in vitro. Tissue Cell, 14:629–636, (1982).
R. R. Schleef and C. R. Birdwell. Biochemical changes in endothelial cell monolayers induced by fibrin deposition in vitro. Atherosclerosis,4:13–20, 1984.
J. A. Ribes, C. W. Francis, and D. D. Wanger. Fibrin induces release of von Willebrand factor from endothelial cells. J. Clin. Invest, 79:117–123, (1987).
E. G. Levin, U. Marzec, J. Anderson, and L. A. Harker. Thrombin stimulates tissue plasmnogen activator release from cultured human endothelial cells. J. Clin. Invest, 74:1984–1995 (1984).
E. G. Levin, D. M. Stern, P. P. Nawroth, R. A. Marlar, D. S. Fair, J. W. Fenton 2nd, and L. A. Harker. Specificity of the thrombin-induced release of tissue plasminogen activator from cultured human endothelial cells. Thromb. Haemost, 52:115–119, (1986).
B. B. Weksler, C. W. Ley, and E. A. Jaffe. Stimulation of endothelial cell prostacyclin production by thrombin, trypsin, and the ionophore A23187. J. Clin. Invest, 62:923–930, (1978).
S. L. Hong. Effect of bradykinin and thrombin on prostacyclin synthesis in endothelial cells from calf and pig aorta and human umbilical vein. Thrombosis Res, 18:787–795, (1980).
A. P. Laudano and R. F. Doolittle. Studies on synthetic peptides that bind to fibrinogen and prevent fibrin polymerization. Structural requirements, number of binding sites, and species differences. Biochemistry, 19:1013–1019 (1980).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1990 Springer Science+Business Media New York
About this chapter
Cite this chapter
Kaplan, K.L., Bini, A., Fenoglio, J., Kudryk, B. (1990). Fibrin and the Vessel Wall. In: Liu, C.Y., Chien, S. (eds) Fibrinogen, Thrombosis, Coagulation, and Fibrinolysis. Advances in Experimental Medicine and Biology, vol 281. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3806-6_33
Download citation
DOI: https://doi.org/10.1007/978-1-4615-3806-6_33
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-6697-3
Online ISBN: 978-1-4615-3806-6
eBook Packages: Springer Book Archive