Thromb Haemost 1998; 79(03): 500-508
DOI: 10.1055/s-0037-1614933
Review Articles
Schattauer GmbH

Abnormal Expression of Type 1 Plasminogen Activator Inhibitor and Tissue Factor in Severe Preeclampsia

Amparo Estellés
1   Centro de Investigación and Centro Maternal, Hospital La Fe, Valencia, Spain
,
Juan Gilabert
2   Centro Maternal, Hospital La Fe, Valencia, Spain The Scripps Research Institute, Department of Vascular Biology, La Jolla, CA, USA
,
Salvador Grancha
1   Centro de Investigación and Centro Maternal, Hospital La Fe, Valencia, Spain
,
Koji Yamamoto
3   The Scripps Research Institute, Department of Vascular Biology, La Jolla, CA, USA
,
Terri Thinnes
3   The Scripps Research Institute, Department of Vascular Biology, La Jolla, CA, USA
,
Francisco España
1   Centro de Investigación and Centro Maternal, Hospital La Fe, Valencia, Spain
,
Justo Aznar
1   Centro de Investigación and Centro Maternal, Hospital La Fe, Valencia, Spain
,
David Loskutoff
3   The Scripps Research Institute, Department of Vascular Biology, La Jolla, CA, USA
› Author Affiliations
Further Information

Publication History

Received 16 June 1997

Accepted after revision 05 November 1997

Publication Date:
07 December 2017 (online)

Summary

Preeclampsia is a multisystemic obstetric disease of unknown etiology that is commonly associated with fibrin deposition, occlusive lesions in placental vasculature, and intrauterine fetal growth retardation. We previously reported that type 1 plasminogen activator inhibitor (PAI-1) levels are significantly increased in plasma and placenta from pregnant women with preeclampsia compared to normal pregnant women. In the present report we localize the expression of placental PAI-1 in greater detail and compare it with that of tissue factor (TF), a procoagulant molecule, and vitronectin (Vn), a PAI-1 cofactor. We also examine the expression of two cytokines, tumor necrosis factor α (TNFα) and interleukin-1 (IL-1), in order to begin to define the underlying mechanisms responsible for the elevated levels of PAI-1 and fibrin deposits observed in placenta from preeclampsia. We demonstrate a significant increase in PAI-1, TF and TNFα antigen and PAI-1 and TF mRNA in placentas from preeclamptic patients. PAI-1 mRNA was increased not only in syncytiotrophoblast and infarction areas, but also in fibroblasts and in some endothelial cells of fetal vessels in placentas from preeclamptic patients. However, there was no colocalization between PAI-1, TF, Vn and TNFα in placental villi. The elevated TNFα in the placenta may induce PAI-1 and TF, and thus promote the thrombotic alterations associated with preeclampsia.

 
  • References

  • 1 De Wolf F, Robertson WB, Brosens I. The ultrastructure of acute atherosis in hypertensive pregnancy.. Am J Obstet Gynecol 1975; 123: 164-74.
  • 2 Canavagh D, Kmuppel LA. Preeclampsia and eclampsia.. In: Principles and Practice of Obstetrics and Perinatology.. Iffy L, Kaminetzky H. eds. John Wiley & Sons; New York, NY: 1981. pp 1271-89.
  • 3 Hathaway W, Bonnar J. Hemostatic alterations in hypertensive and placental insufficiency disorders of pregnancy.. In: Hemostatic Disorders of the Pregnant Woman and Newborn Infant.. Hathaway W, Bonnar J. eds. John Wiley & Sons; New York, NY: 1987. pp 185-201.
  • 4 Pijnenborg R, Anthony J, Davey JA, Rees A, Tiltman A, Vercruysse L, Van Assche A. Placental bed spiral arteries in the hypertensive disorders of pregnancy.. Br J Obstet Gynecol 1991; 88: 695-705.
  • 5 Benirschke K, Kaufmann P. Hypertensive disorders.. In: Pathology of the human placenta.. Benirschke K, Kaufmann P. eds. Springer-Verlag; New York, NY: 1990. pp 499-529.
  • 6 Brown MA. The physiology of preeclampsia.. Clin Exp Pharmacol P 1995; 22: 781-91.
  • 7 Kruithof EKO, Tran-Thang C, Gudinchet A, Havert J, Nicoloso G, Genton C, Welti H, Bachmann F. Fibrinolysis in pregnancy: A study of plasminogen activator inhibitors.. Blood 1987; 69: 460-6.
  • 8 Estellés A, Gilabert J, Aznar J, Loskutoff DJ, Schleef RR. Changes in the plasma levels of type 1 and type 2 plasminogen activator inhibitors in normal pregnancy and in patients with severe preeclampsia.. Blood 1989; 74: 1332-8.
  • 9 Estellés A, Gilabert J, Keeton M, Eguchi Y, Aznar J, Grancha S, España F, Loskutoff DJ, Schleef RR. Altered expression of plasminogen activator inhibitor type 1 in placentas from pregnant women with preeclampsia and/or intrauterine fetal growth retardation.. Blood 1994; 84: 143-50.
  • 10 Camerer E, Kolsto A-B, Prydz H. Cell biology of tissue factor. The principal initiator of blood coagulation.. Thromb Res 1996; 81: 1-41.
  • 11 Spicer EK, Horton R, Bloem L, Bach R, Williams KR, Guha A, Kraus J, Lin T-C, Nemerson Y, Konigsberg WH. Isolation and cDNA clones coding for human tissue factor: primary structure of the protein and cDNA.. Proc Natl Acad Sci USA 1987; 84: 5148-52.
  • 12 Loskutoff DJ. Regulation of PAI-1 gene expression.. Fibrinolysis 1991; 5: 197-206.
  • 13 Sprengers ED, Kluft C. Plasminogen activator inhibitors.. Blood 1987; 69: 381-7.
  • 14 Sawdey M, Podor TJ, Loskutoff DJ. Regulation of type 1 plasminogen activator inhibitor gene. Expression in cultured bovine aortic endothelial cells, induction by transforming growth factor-β, lipopolysaccharide, and tumor necrosis factor-α.. J Biol Chem 1989; 264: 10396-401.
  • 15 Sawdey M, Loskutoff DJ. Regulation of murine type 1 plasminogen activator inhibitor gene expression in vivo. Tissue specificity and induction by lipopolysaccharide, tumor necrosis factor-α, and transforming growth factor-β.. J Clin Invest 1991; 88: 1346-53.
  • 16 Declerck PJ, De Mol M, Alessi M-C, Baudner S, Paques E-P, Preissner KT, Müller-Barghaus G, Collen D. Purification and characterization of a plasminogen activator inhibitor 1 binding protein from human plasma.. J Biol Chem 1988; 263: 15454-61.
  • 17 Mimuro J, Loskutoff DJ. Purification of a protein from bovine plasma that binds to type 1 plasminogen activator inhibitor and prevents its interaction with extracellular matrix. Evidence that the protein is vitronectin.. J Biol Chem 1989; 264: 936-9.
  • 18 Deng G, Royle G, Seiffert D, Loskutoff DJ. The PAI-1/vitronectin interaction: two cats in a bag?. Thromb Haemost 1995; 74: 66-70.
  • 19 Radtke KP, Wenz K-H, Heimburger N. Isolation of plasminogen activator inhibitor-2 (PAI-2) from human placenta. Evidence for vitronectin/PAI-2 complexes in human placenta extract.. Biol Chem Hoppe-Seyler 1990; 371: 1119-27.
  • 20 Watanabe T, Araki M, Mimuro J, Tamada T, Sakata Y. Fibrinolytic components in fetal membranes and amniotic fluid.. Am J Obstet Gynecol 1993; 168: 1283-9.
  • 21 Robbie LA, Booth NA, Brown PAJ, Bennett B. Inhibitors of fibrinolysis are elevated in atherosclerotic plaque.. Arterioscler Thromb Vasc Biol 1996; 16: 539-45.
  • 22 van Aken BE, Seiffert D, Thinnes T, Loskutoff DJ. Localization of vitronectin in the normal and atherosclerotic human vessel wall.. Histochem Cell Biol 1997; 107: 313-20.
  • 23 Estellés A, Gilabert J, España F, Aznar J, Galbis M. Fibrinolytic parameters in normotensive pregnancy with intrauterine fetal growth retardation and in severe preeclampsia.. Am J Obstet Gynecol 1991; 165: 138-42.
  • 24 Ballegeer V, Spitz B, Kieckens L, Moreau H, Van Assche A, Collen D. Predictive value of increased plasma levels fibronectine in gestational hyper-tension.. Am J Obstet Gynecol 1991; 161: 432-6.
  • 25 Caron C, Goudemand J, Marey A, Beagne D, Ducroux G, Drouvin F. Are the hemostatic and fibrinolytic parameters predictors of preeclampsia in pregnancy-associated hypertension?. Thromb Haemost 1991; 66: 410-4.
  • 26 Reith A, Booth NA, Moore NR, Cruickshank DJ, Bennett B. Plasminogen activator inhibitors (PAI-1 and PAI-2) in normal pregnancies, preeclampsia and hydatidiform mole.. Br J Obstet Gynecol 1993; 100: 370-4.
  • 27 Halligan A, Bonnar J, Sheppard B, Darling M, Walshe J. Haemostatic, fibrinolytic and endothelial variables in normal pregnancies and preeclampsia.. Br J Obstet Gynecol 1994; 101: 488-92.
  • 28 Friedman SA, Schiff E, Emeis JJ, Dekker GA, Sibai BM. Biochemical corroboration of endothelial involvement in severe preeclampsia.. Am J Obstet Gynecol 1995; 172: 202-3.
  • 29 Jaattela M, Kuusela P, Sakkela E. Demonstration of tumor necrosis factor in human amniotic fluids and supernatants of placental and decidual tissues.. Lab Invest 1988; 58: 48-52.
  • 30 Eades DK, Cornelius P, Pekala PH. Characterization of the tumor necrosis factor receptor in human placenta.. Placenta 1988; 9: 247-51.
  • 31 Chen H-L, Yang Y, Hu X-L, Yelavarthi KK, Fishback JL, Hunt JS. Tumor necrosis factor α mRNA and protein are present in human placental and uterine cells at early and late stages of gestation.. Am J Pathol 1991; 139: 327-35.
  • 32 Kauma S, Matt D, Strom S, Eierman D, Turner T. Interleukin-1β, human leukocyte antigen HA-DRα, and transforming growth factorβ expression in endometrium, placenta, and placental membranes.. Am J Obstet Gynecol 1990; 163: 1430-7.
  • 33 Wolf HK, Zarnegar R, Oliver L, Michalopoulos GK. Hepatocyte growth factor in human placenta and trophoblastic disease.. Am J Pathol 1991; 138: 1035-43.
  • 34 Cunninghan FG, MacDonald PC, Gant NF. In: Williams’ Obstetrics. Eighteenth Edition. Appleton & Lange; Connecticut/San Mateo, CA, Norwalk: 1987
  • 35 Keeton M, Eguchi Y, Sawdey M, Loskutoff DJ. Cellular localization of type-1 plasminogen activator inhibitor messenger RNA and protein in murine renal tissue.. Am J Pathol 1991; 142: 59-70.
  • 36 Schleef RR, Podor TJ, Dunne E, Mimuro J, Loskutoff DJ. The majority of type 1 plasminogen activator inhibitor associated with cultured human endothelial cells is located under the cells and is accessible to solution-phase tissue-type plasminogen activator.. J Cell Biol 1990; 110: 155-63.
  • 37 Seiffert D, Ciambrone G, Wagner NV, Binder BR, Loskutoff DJ. The somatomedin B domain of vitronectin. Structural requirements for the binding and stabilization of active type 1 plasminogen activator inhibitor.. J Biol Chem 1994; 269: 2659-66.
  • 38 Garvey W, Fathi A, Bigelow F, Carpenter B, Jimenez C. A combined elastic, fibrin and collagen stain.. Stain Technology 1987; 62: 365-7.
  • 39 Schneiderman J, Sawdey MS, Keeton MR, Bordin GM, Bernstein EF, Dilley RB, Loskutoff DJ. Increased type 1 plasminogen activator inhibitor gene expression in atherosclerotic human arteries.. Proc Natl Acad Sci USA 1992; 89: 6998-7002.
  • 40 Jenne D, Stanley KK. Molecular cloning of S-protein, a link between complement, coagulation and cell-substrate adhesion.. EMBO J 1985; 4: 3153-7.
  • 41 Wilcox JN, Smith KM, Schmartz SM, Gordon D. Localization of tissue factor in the normal vessel wall and in the atherosclerotic plaque.. Proc Natl Acad Sci USA 1989; 86: 2839-43.
  • 42 Samad F, Yamamoto K, Loskutoff DJ. Distribution and regulation of plasminogen activator inhibitor-1 in murine adipose tissue in vivo: Induction of tumor necrosis factor-α and lipopolysaccharide.. J Clin Invest 1996; 97: 37-46.
  • 43 Yamamoto K, Loskutoff DJ. Fibrin deposition in tissues from endotoxin-treated mice correlates with decreases in the expression of urokinase-type but not tissue-type plasminogen activator.. J Clin Invest 1996; 97: 2440-51.
  • 44 Tokunaga K, Taniguchi K, Yoda K, Shimizu M, Sakiyama S. Nucleotide sequence of a full-length cDNA for mouse cytoskeletal β actin mRNA.. Nucleic Acids Res 1997; 14: 2829.
  • 45 Wang AM, Doyle MV, Mark DF. Quantitation of mRNA by the polymerase chain reaction.. Proc Natl Acad Sci USA 1989; 86: 9717-21.
  • 46 Feinberg RF, Kao L-C, Haimowitz JE, Queenan Jr JT, Wun T-C, Strauss III JF, Kliman HJ. Plasminogen activator inhibitor types 1 and 2 in human trophoblasts. PAI-1 is an immunocytochemical marker of invading tropho-blasts.. Lab Invest 1989; 61: 20-6.
  • 47 Estellés A, Gilabert J, Aznar J, España F, Schleef R, Loskutoff DJ. Cellular expression and potential roles of plasminogen activator inhibitors in normal and pathological pregnancies.. In: Fibrinolytic inhibitors. Cellular, biological and clinical aspects.. Aznar J, Gilabert J, Estellés A. eds. Garsi-Masson; Spain,: 1994. pp 43-59.
  • 48 Gilabert J, Estellés A, Aznar J, España F, Andrés C, Santos T, Vallés J. Contribution of platelets to increased plasminogen activator inhibitor type 1 in severe preeclampsia.. Thromb Haemost 1990; 63: 361-6.
  • 49 He S, Bream K, Blombäck M. Increased blood flow resistance in placental circulation and levels of plasminogen activator inhibitors types 1 and 2 in severe preeclampsia.. Blood Coagul Fibrin 1995; 6: 703-8.
  • 50 Graeff H, Von Hugo R, Schrock R. Recent aspects of hemostasis, hematology and hemorrheology in preeclampsia-eclampsia.. Eur J Obstet Gynec Reprod Biol 1984; 17: 91-102.
  • 51 Estellés A, Gilabert J, España F, Aznar J, Gómez-Lechón MJ. Fibrinolysis in preeclampsia.. Fibrinolysis 1987; 1: 209-13.
  • 52 Fox H. Placental pathology: a contemporary approach.. In: Obstetrics and Gynecology Annual.. Vol 14. Wynn RM. ed. Appleton-Century-Crofts; Connecticut: 1985. pp 427-40.
  • 53 Chen G, Wilson R, Wang SH, Zheng HZ, Walker JJ, Mckillop JH. Tumour necrosis factor-alpha (TNF-alpha) gene polymorphism and expression in pre-eclampsia.. Clin Exp Immunol 1996; 104: 154-9.
  • 54 Kanfer A, Bruch JF, Nguyen G, He CJ, Delarue F, Flahaut A, Nessmann C, Uzan S. Increased placental antifibrinolytic potential and fibrin deposits in pregnancy-induced hypertension and preeclampsia.. Lab Invest 1996; 74: 253-8.
  • 55 Lucore CL, Fujii S, Wun T-C, Burton BE, Billadello JJ. Regulation of the expression of type 1 plasminogen activator inhibitor in Hep G2 cells by epidermal growth factor.. J Biol Chem 1988; 263: 15845-8.
  • 56 Sawdey M, Loskutoff DJ. Regulation of type one plasminogen activator inhibitor gene expression in cultured endothelial cells and the vessel wall.. In: Arteriosclerosis: Cellular and Molecular Interactions in the Artery Wall.. Fedoroff S. ed. Plenum Publishing Corp.; New York, NY: 1991. pp 187-208.
  • 57 Schneiderman J, Bordin GM, Engelberg I, Adar R, Seiffert D, Thinnes T, Bernstein EF, Dilley RB, Loskutoff DJ. Expression of fibrinolytic genes in atherosclerotic abdominal aortic aneurysm wall.. J Clin Invest 1995; 96: 639-45.
  • 58 Edgington TS, Mackman N, Brand K, Ruf W. The structural biology of expression and function of tissue factor.. Thromb Haemost 1991; 66: 67-9.