Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 Apr;86(8):2839–2843. doi: 10.1073/pnas.86.8.2839

Localization of tissue factor in the normal vessel wall and in the atherosclerotic plaque.

J N Wilcox 1, K M Smith 1, S M Schwartz 1, D Gordon 1
PMCID: PMC287014  PMID: 2704749

Abstract

Tissue factor (TF)-producing cells were identified in normal human vessels and atherosclerotic plaques by in situ hybridization and immunohistochemistry using a specific riboprobe for TF mRNA and a polyclonal antibody directed against human TF protein. TF mRNA and protein were absent from endothelial cells lining normal internal mammary artery and saphenous vein samples. In normal vessels TF was found to be synthesized in scattered cells present in the tunica media as well as fibroblast-like adventitial cells surrounding vessels. Atherosclerotic plaques contained many cells synthesizing TF mRNA and protein. Macrophages present as foam cells and monocytes adjacent to the cholesterol clefts contained TF mRNA and protein, as did mesenchymal-appearing intimal cells. Significant TF protein staining was found deposited in the extracellular matrix surrounding mRNA-positive cells adjacent to the cholesterol clefts and within the necrotic cores. These results suggest that deposition of TF protein in the matrix of the necrotic core of the atherosclerotic plaque may contribute to the hyperthrombotic state of human atherosclerotic vessels.

Full text

PDF
2841

Images in this article

2840Image
on p.2840

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bevilacqua M. P., Pober J. S., Wheeler M. E., Cotran R. S., Gimbrone M. A., Jr Interleukin-1 activation of vascular endothelium. Effects on procoagulant activity and leukocyte adhesion. Am J Pathol. 1985 Dec;121(3):394–403. [PMC free article] [PubMed] [Google Scholar]
  2. Bjørklid E., Holm T., Osterud B. The development of monospecific antibodies against human thromboplastin apoprotein (apoprotein III) and their application in the immunocytochemical detection of the antigen in blood cells. Thromb Res. 1987 Mar 1;45(5):609–624. doi: 10.1016/0049-3848(87)90324-0. [DOI] [PubMed] [Google Scholar]
  3. Brox J. H., Osterud B., Bjørklid E., Fenton J. W., 2nd Production and availability of thromboplastin in endothelial cells: the effects of thrombin, endotoxin and platelets. Br J Haematol. 1984 Jun;57(2):239–246. doi: 10.1111/j.1365-2141.1984.tb02892.x. [DOI] [PubMed] [Google Scholar]
  4. Buja L. M., Willerson J. T. Clinicopathologic correlates of acute ischemic heart disease syndromes. Am J Cardiol. 1981 Feb;47(2):343–356. doi: 10.1016/0002-9149(81)90407-0. [DOI] [PubMed] [Google Scholar]
  5. CHAPMAN I. MORPHOGENESIS OF OCCLUDING CORONARY ARTERY THROMBOSIS. Arch Pathol. 1965 Sep;80:256–261. [PubMed] [Google Scholar]
  6. Constantinides P. Pathogenesis of cerebral artery thrombosis in man. Arch Pathol. 1967 May;83(5):422–428. [PubMed] [Google Scholar]
  7. DRURY R. A. The role of intimal haemorrhage in coronary occlusion. J Pathol Bacteriol. 1954 Jan;67(1):207–215. doi: 10.1002/path.1700670125. [DOI] [PubMed] [Google Scholar]
  8. Davies M. J., Woolf N., Robertson W. B. Pathology of acute myocardial infarction with particular reference to occlusive coronary thrombi. Br Heart J. 1976 Jul;38(7):659–664. doi: 10.1136/hrt.38.7.659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. DeWood M. A., Spores J., Notske R., Mouser L. T., Burroughs R., Golden M. S., Lang H. T. Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction. N Engl J Med. 1980 Oct 16;303(16):897–902. doi: 10.1056/NEJM198010163031601. [DOI] [PubMed] [Google Scholar]
  10. Falk E. Plaque rupture with severe pre-existing stenosis precipitating coronary thrombosis. Characteristics of coronary atherosclerotic plaques underlying fatal occlusive thrombi. Br Heart J. 1983 Aug;50(2):127–134. doi: 10.1136/hrt.50.2.127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fisher K. L., Gorman C. M., Vehar G. A., O'Brien D. P., Lawn R. M. Cloning and expression of human tissue factor cDNA. Thromb Res. 1987 Oct 1;48(1):89–99. doi: 10.1016/0049-3848(87)90349-5. [DOI] [PubMed] [Google Scholar]
  12. Forrester J. S., Litvack F., Grundfest W., Hickey A. A perspective of coronary disease seen through the arteries of living man. Circulation. 1987 Mar;75(3):505–513. doi: 10.1161/01.cir.75.3.505. [DOI] [PubMed] [Google Scholar]
  13. Friedman M. The coronary thrombus: its origin and fate. Hum Pathol. 1971 Mar;2(1):81–128. doi: 10.1016/s0046-8177(71)80022-9. [DOI] [PubMed] [Google Scholar]
  14. Friedman M., Van den Bovenkamp G. J. The pathogenesis of a coronary thrombus. Am J Pathol. 1966 Jan;48(1):19–44. [PMC free article] [PubMed] [Google Scholar]
  15. Gown A. M., Tsukada T., Ross R. Human atherosclerosis. II. Immunocytochemical analysis of the cellular composition of human atherosclerotic lesions. Am J Pathol. 1986 Oct;125(1):191–207. [PMC free article] [PubMed] [Google Scholar]
  16. Green D., Ryan C., Malandruccolo N., Nadler H. L. Characterization of the coagulant activity of cultured human fibroblasts. Blood. 1971 Jan;37(1):47–51. [PubMed] [Google Scholar]
  17. Holthöfer H., Virtanen I., Kariniemi A. L., Hormia M., Linder E., Miettinen A. Ulex europaeus I lectin as a marker for vascular endothelium in human tissues. Lab Invest. 1982 Jul;47(1):60–66. [PubMed] [Google Scholar]
  18. Horie T., Sekiguchi M., Hirosawa K. Coronary thrombosis in pathogenesis of acute myocardial infarction. Histopathological study of coronary arteries in 108 necropsied cases using serial section. Br Heart J. 1978 Feb;40(2):153–161. doi: 10.1136/hrt.40.2.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Imparato A. M., Riles T. S., Mintzer R., Baumann F. G. The importance of hemorrhage in the relationship between gross morphologic characteristics and cerebral symptoms in 376 carotid artery plaques. Ann Surg. 1983 Feb;197(2):195–203. doi: 10.1097/00000658-198302000-00012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Jonasson L., Holm J., Skalli O., Bondjers G., Hansson G. K. Regional accumulations of T cells, macrophages, and smooth muscle cells in the human atherosclerotic plaque. Arteriosclerosis. 1986 Mar-Apr;6(2):131–138. doi: 10.1161/01.atv.6.2.131. [DOI] [PubMed] [Google Scholar]
  21. Levy G. A., Schwartz B. S., Curtiss L. K., Edgington T. S. Plasma lipoprotein induction and suppression of the generation of cellular procoagulant activity in vitro. J Clin Invest. 1981 Jun;67(6):1614–1622. doi: 10.1172/JCI110196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lyberg T., Galdal K. S., Evensen S. A., Prydz H. Cellular cooperation in endothelial cell thromboplastin synthesis. Br J Haematol. 1983 Jan;53(1):85–95. doi: 10.1111/j.1365-2141.1983.tb01989.x. [DOI] [PubMed] [Google Scholar]
  23. Lyberg T., Nilsson K., Prydz H. Synthesis of thromboplastin by U-937 cells. Br J Haematol. 1982 Aug;51(4):631–641. doi: 10.1111/j.1365-2141.1982.tb02827.x. [DOI] [PubMed] [Google Scholar]
  24. Maynard J. R., Dreyer B. E., Stemerman M. B., Pitlick F. A. Tissue-factor coagulant activity of cultured human endothelial and smooth muscle cells and fibroblasts. Blood. 1977 Sep;50(3):387–396. [PubMed] [Google Scholar]
  25. Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Morrissey J. H., Fakhrai H., Edgington T. S. Molecular cloning of the cDNA for tissue factor, the cellular receptor for the initiation of the coagulation protease cascade. Cell. 1987 Jul 3;50(1):129–135. doi: 10.1016/0092-8674(87)90669-6. [DOI] [PubMed] [Google Scholar]
  27. Nawroth P. P., Handley D. A., Esmon C. T., Stern D. M. Interleukin 1 induces endothelial cell procoagulant while suppressing cell-surface anticoagulant activity. Proc Natl Acad Sci U S A. 1986 May;83(10):3460–3464. doi: 10.1073/pnas.83.10.3460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Nawroth P. P., Stern D. M. Modulation of endothelial cell hemostatic properties by tumor necrosis factor. J Exp Med. 1986 Mar 1;163(3):740–745. doi: 10.1084/jem.163.3.740. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Nemerson Y., Bach R. Tissue factor revisited. Prog Hemost Thromb. 1982;6:237–261. [PubMed] [Google Scholar]
  30. Nemerson Y. Regulation of the initiation of coagulation by factor VII. Haemostasis. 1983;13(3):150–155. doi: 10.1159/000214720. [DOI] [PubMed] [Google Scholar]
  31. Nemerson Y. The reaction between bovine brain tissue factor and factors VII and X. Biochemistry. 1966 Feb;5(2):601–608. doi: 10.1021/bi00866a029. [DOI] [PubMed] [Google Scholar]
  32. Nemerson Y. Tissue factor and hemostasis. Blood. 1988 Jan;71(1):1–8. [PubMed] [Google Scholar]
  33. Osterud B., Rapaport S. I. Activation of factor IX by the reaction product of tissue factor and factor VII: additional pathway for initiating blood coagulation. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5260–5264. doi: 10.1073/pnas.74.12.5260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Rosenthal A., Chan S. Y., Henzel W., Haskell C., Kuang W. J., Chen E., Wilcox J. N., Ullrich A., Goeddel D. V., Routtenberg A. Primary structure and mRNA localization of protein F1, a growth-related protein kinase C substrate associated with synaptic plasticity. EMBO J. 1987 Dec 1;6(12):3641–3646. doi: 10.1002/j.1460-2075.1987.tb02696.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Ross R. The pathogenesis of atherosclerosis--an update. N Engl J Med. 1986 Feb 20;314(8):488–500. doi: 10.1056/NEJM198602203140806. [DOI] [PubMed] [Google Scholar]
  36. Scarpati E. M., Wen D., Broze G. J., Jr, Miletich J. P., Flandermeyer R. R., Siegel N. R., Sadler J. E. Human tissue factor: cDNA sequence and chromosome localization of the gene. Biochemistry. 1987 Aug 25;26(17):5234–5238. doi: 10.1021/bi00391a004. [DOI] [PubMed] [Google Scholar]
  37. Sherman C. T., Litvack F., Grundfest W., Lee M., Hickey A., Chaux A., Kass R., Blanche C., Matloff J., Morgenstern L. Coronary angioscopy in patients with unstable angina pectoris. N Engl J Med. 1986 Oct 9;315(15):913–919. doi: 10.1056/NEJM198610093151501. [DOI] [PubMed] [Google Scholar]
  38. Spicer E. K., Horton R., Bloem L., Bach R., Williams K. R., Guha A., Kraus J., Lin T. C., Nemerson Y., Konigsberg W. H. Isolation of cDNA clones coding for human tissue factor: primary structure of the protein and cDNA. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5148–5152. doi: 10.1073/pnas.84.15.5148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Stern D. M., Drillings M., Kisiel W., Nawroth P., Nossel H. L., LaGamma K. S. Activation of factor IX bound to cultured bovine aortic endothelial cells. Proc Natl Acad Sci U S A. 1984 Feb;81(3):913–917. doi: 10.1073/pnas.81.3.913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Tipping P. G., Campbell D. A., Boyce N. W., Holdsworth S. R. Alveolar macrophage procoagulant activity is increased in acute hyperoxic lung injury. Am J Pathol. 1988 May;131(2):206–212. [PMC free article] [PubMed] [Google Scholar]
  41. Tsukada T., Tippens D., Gordon D., Ross R., Gown A. M. HHF35, a muscle-actin-specific monoclonal antibody. I. Immunocytochemical and biochemical characterization. Am J Pathol. 1987 Jan;126(1):51–60. [PMC free article] [PubMed] [Google Scholar]
  42. Wilcox J. N., Smith K. M., Williams L. T., Schwartz S. M., Gordon D. Platelet-derived growth factor mRNA detection in human atherosclerotic plaques by in situ hybridization. J Clin Invest. 1988 Sep;82(3):1134–1143. doi: 10.1172/JCI113671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Zaugg H. Thromboplastic activity of human arterial walls and its interaction with the plasmatic coagulation system. J Clin Chem Clin Biochem. 1980 Sep;18(9):545–549. doi: 10.1515/cclm.1980.18.9.545. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES