Download PDF
Thromb Haemost 1995; 74(01): 429-436
DOI: 10.1055/s-0038-1642716
Symposium
Plenary Lecture
Schattauer GmbH Stuttgart

Gene Targeting and Gene Transfer Studies of the Biological Role of the Plasminogen/Plasmin System

Peter Carmeliet
Center for Transgene Technology and Gene Therapy, Vlaams Interuniversitair Instituut voor Biotechnologie, Campus Gasthuisberg, Leuven, Belgium
,
Désiré Collen
Center for Transgene Technology and Gene Therapy, Vlaams Interuniversitair Instituut voor Biotechnologie, Campus Gasthuisberg, Leuven, Belgium
› Author Affiliations
Further Information

Publication History

Publication Date:
09 July 2018 (online)

  PDF Download  Permissions and Reprints
 

  • References

  • 1 Astrup T. In: Progress in Chemical Fibrinolysis and Thrombolysis. Vol 3 . Davidson JF, Rowan RM, Samama MM, Desnoyers PC. eds. Raven Press; New Yorie: 1978: 1-57
  • 2 Collen D, Lijnen HR. Basic and clinical aspects of fibrinolysis and thrombolysis. Blood 1991; 78: 3114-3124
    PubMedGoogle Scholar
  • 3 Blasi F, Vassalli JD, Dano K. Urokinase-type plasminogen activator: proenzyme, receptor, and inhibitors. J Cell Biol 1987; 104: 801-804
    CrossrefPubMedGoogle Scholar
  • 4 Vassalli JD. The Urokinase Receptor. Fibrinolysis 1994; 8 (01) 172-181
    PubMedGoogle Scholar
  • 5 Schneideiman J, Loskutoff DJ. Plasminogen activator inhibitors. Trends Cardiovasc Med 1991; 1: 99-102
    CrossrefPubMedGoogle Scholar
  • 6 Andreasen PA, Sottmp-Jensen LI. et al. Receptor-mediated endocytosis of plasminogen activators and activator/inhibitor complexes. FEBS Letters 1994; 338: 239-245
    CrossrefPubMedGoogle Scholar
  • 7 Richards WG, Carroll PM, KinlochR A, Wassarman PM, Strickland S. Creating maternal effect mutations in transgenic mice: antisense inhibition of an oocyte gene product. Develop Biol 1993; 160: 543-553
    CrossrefPubMedGoogle Scholar
  • 8 Erickson LA, Fici GJ, Lund JE, Boyle TP, Polites HG, Marotti KR. Development of venous occlusions in mice transgenic for the plasminogen activator inhibitor-1 gene. Nature 1990; 346: 74-76
    CrossrefPubMedGoogle Scholar
  • 9 Heckel JL, Sandgren EP, Degen JL, Palmiter RD, Brinster RL. Neonatal bleeding in transgenic mice expressing urokinase-type plasminogen activator. Cell 1990; 62: 447-456
    CrossrefPubMedGoogle Scholar
  • 10 Meiri N, Masos T, Rosenblum K, Miskin R, Dudai Y. Overexpression of urokinase-type plasminogen activator in transgenic mice is correlated with impaired learning. Proc Natl Acad Sci USA 1994; 91: 3196-3200
    CrossrefPubMedGoogle Scholar
  • 11 Sidenius N. Expression of the aminoteiminal fragment of urokinase-type plasminogen activator in transgenic mice. PhD.thesis. University of Copenhagen; Denmark: 1993
    Google Scholar
  • 12 Carmeliet P, Schoonjans L, Kieckens L, Ream B, Degen J, Bronson R, De Vos R, van den Oord JJ, Collen D, Mulligan R. Physiological consequences of loss of plasminogen activator gene function in mice. Nature 1994; 368: 419-424
    CrossrefPubMedGoogle Scholar
  • 13 Carmeliet P, De Clercq C, Janssen S, Pollefeyt S, Bouche A, Wijns S, Mulligan RC, Collen D. Biological effects of disruption of the tissue-type plasminogen activator, urokinase-type plasminogen activator and plasminogen activator inhibitor-1 genes in mice. Ann NY Acad Sci. (in press)
    PubMedGoogle Scholar
  • 14 Carmeliet P, Kieckens L, Schoonjans L, Ream B, Van Nuffelen A, Prendergast G, Cole M, Bronson R, Collen D, Mulligan RC. Plasminogen activator inhibitor-1 gene-deficient mice. I. Generation by homologous recombination and characterization. J Clin Invest 1993; 92: 2746-2755
    CrossrefPubMedGoogle Scholar
  • 15 Carmeliet P, Stassen JM, Schoonjans L, Ream B, van den Oord JJ, De Mol M, Mulligan RC, Collen D. Plasminogen activator inhibitor-1 gene-deficient mice. II. Effects cm hemostasis, thrombosis and thrombolysis. J Clin Invest 1993; 92: 2756-2760
    CrossrefPubMedGoogle Scholar
  • 16 Herz J, Clouthier DE, Hammer RE. LDL receptor-related protein internalizes and degrades uPA:PAI-l complexes and is essential for embryo implantation. Cell 1992; 71: 411-421
    CrossrefPubMedGoogle Scholar
  • 17 Umans L, Semeels L, Stas L, Overbergh L, Van Leuven F, Van den Berghe H. Targeted inactivation of the mouse alphaj-Macroglobulin gene results in a viable phenotype (submitted).
    PubMedGoogle Scholar
  • 18 Dewerchin M, Carmeliet P, Van Nuffelen A, Collen D, and Mulligan RO M. Inactivation of the mouse urokinase receptor gene. Fibrinolysis 1994; 8 Suppl (Suppl. 01) A142
    PubMedGoogle Scholar
  • 19 Ploplis V, Carmeliet P, Vazirzadeh S, Van Vlaenderen I, Stassen JM, Plow E, Collen D. Targeted inactivation of the murine plasminogen gene (Thrombosis and Haemostasis; this meeting).
    PubMedGoogle Scholar
  • 20 Vassalli JD, Sappino JD, Belin D. The plasminogen activator/plasmin system. J Clin Invest 1991; 88: 1067-1072
    CrossrefPubMedGoogle Scholar
  • 21 Kluft C, Dooijewaard G, Emeis JJ. Role of the contact system in fibrinolysis. Sem. Thromb Hemost 1987; 13: 50-68
    Article in Thieme ConnectPubMedGoogle Scholar
  • 22 Plow EF, Edgington TS. An alternative pathway for fibrinolysis. I. The cleavage of fibrinogen by leukocyte proteases at physiologic pH. J Clin Invest 1975; 56: 30-38
    CrossrefPubMedGoogle Scholar
  • 23 Hamsten A, de Faire U, Walldius G. et al. Plasminogen activator inhibitor in plasma:. risk factor for recurrent myocardial infarction.. Lancet 1987; 2: 3-9
    PubMedGoogle Scholar
  • 24 Aoki N. Hemostasis associated with abnormalities of fibrinolysis. Blood Rev 1989; 3: 11-17
    CrossrefPubMedGoogle Scholar
  • 25 Carmeliet P, Stassen JM, Declercq C, Collen D. Arterial neointima formation in mice with inactivated plasminogen/plasmin system genes (submitted).
    PubMedGoogle Scholar
  • 26 Carmeliet P, Stassen JM, Collen D, Meidell R, and Gerard R. Adenovirus- mediated gene transfer of rt-PA restores thrombolysis in t-PA deficient mice. Fibrinolysis 1994; 8 (01) A282
    PubMedGoogle Scholar
  • 27 Fay WP, Shapiro AD, Shih JL, Schleef RR, Ginsburg D. Complete deficiency of plasminogen-activator inhibitor type 1 due to a frameshift mutation. . N Engl J Med 1992; 327: 1729-1733
    CrossrefPubMedGoogle Scholar
  • 28 Elliott MJ, Faulkner-Jones BE, Stanton H, Hamilton JA, Metcalf D. Plasminogen activator in granulocyte-macrophage-CSF transgenic mice. J Immunol 1992; 149: 3678-3681
    PubMedGoogle Scholar
  • 29 Clowes AW, Clowes MM, An Y PT, Reidy MA, Belin D. Smooth muscle cells express urokinase during mitogenesis and tissue-type plasminogen activator during migration in injured rat carotid artery. Circ Res 1990; 67: 61-67
    CrossrefPubMedGoogle Scholar
  • 30 Jackson CL, Reidy MA. The role of plasminogen activation in smooth muscle cell migration after arterial injury. Ann NY Acad Sci 1992; 667: 141-150
    CrossrefPubMedGoogle Scholar
  • 31 Sawa H, Sobel BE, Fujii S. Potentiation by hypercholesterolemia of the induction of aortic intramural synthesis of plasminogen activator inhibitor type 1 by endothelial injury. Circ Res 1993; 73: 671-680
    CrossrefPubMedGoogle Scholar
  • 32 Herbert JM, Lamarche I, Prabonnaud V, Dol F, Gauthier T. Tissue-type plasminogen activator is a potent mitogen for human aortic smooth muscle cells. J Biol Chem 1994; 269: 3076-3080
    PubMedGoogle Scholar
  • 33 Forrester JS, Fishbein M, Helfant R, Fagin J. A paradigm for restenosis based on cell biology: clues for the development of new preventive therapies. J Am Coll Cardiol 1991; 17: 758-769
    CrossrefPubMedGoogle Scholar
  • 34 Simpson AJ, Booth NA, Moore NR, Bennett B. Distribution of plasminogen activator inhibitor (PAI-1) in tissues. J Clin Pathol 1991; 44: 139-143
    CrossrefPubMedGoogle Scholar
  • 35 Lupu F, Bergonzelli GE, Heim DA, Cousin E, Genton CY, Bachmann F, Kruithof EK O. Localization and production of plasminogen activator inhibitor-1 in human healthy and atherosclerotic arteries. Arterioscler Thromb 1993; 13: 1090-1100
    CrossrefPubMedGoogle Scholar
  • 36 Sawa H, Fujii S, Sobel BE. Augmented arterial wall expression of type-1 plasminogen activator inhibitor induced by thrombosis. Arterioscl Thromb 1992; 12: 1507-1515
    CrossrefPubMedGoogle Scholar
  • 37 Jackson CL, Raines EW, Ross R, Reidy MA. Role of endogenous platelet- derived growth factor in arterial smooth muscle cell migration after balloon catheter injury. Arterioscl Thromb 1993; 13: 1218-1226
    CrossrefPubMedGoogle Scholar
  • 38 Hamsten A, and Eriksson P. Fibrinolysis and Atherosclerosis: and update. Fibrinolysis 1994; 8 (01) 253-262
    PubMedGoogle Scholar
  • 39 Juhan-Vague I, Collen D. On the role of coagulation and fibrinolysis in atherosclerosis. Ann Epidemiol 1992; 2: 427-438
    CrossrefPubMedGoogle Scholar
  • 40 Liu AC, and Lawn RM. Lipoprotein (a) and atherogenesis. Trends Cardiovasc Medicine 1994; 4: 40-44
    PubMedGoogle Scholar
  • 41 Smokovitis A, Kokolis N, Alexaki-Tzivanidou E. Fatty streaks and fibrous plaques in human aorta show increased plasminogen activator activity. Haemostasis 1988; 18: 146-153
    PubMedGoogle Scholar
  • 42 Underwood MJ, De Bono DP. Increased fibrinolytic activity in the intima of atheromatous coronary arteries: protection at a price. Cardiovasc Res 1993; 27: 882-885
    CrossrefPubMedGoogle Scholar
  • 43 Reilly JM, Sicard GA, Lucore CL. Abnormal expression of plasminogen activators in aortic aneurysmal and occlusive disease. J Vase Surg 1994; 19: 865-872
    CrossrefPubMedGoogle Scholar
  • 44 Grainger DJ, Kemp PR, Liu AC, Lawn RM, and Metcalfe JM. Activation of transforming growth factor-6 is inhibited in transgenic apolipoprotein (a) mice. Nature 1994; 370: 460-462
    CrossrefPubMedGoogle Scholar
  • 45 Bertozzi P, Astedt B, Zenzius L, Lynch K, LeMaire F, Zapoli W, Chapman HA. Depressed bronchioalveolar urokinase activity in patients with adult respiratory distress syndrome. N Engl J Med 1990; 322: 890-897
    CrossrefPubMedGoogle Scholar
  • 46 Tomooka S, Border WA, Marshall BC, Noble NA. Glomerular matrix accumulation is linked to inhibition of the plasmin protease system. Kidney Internal 1992; 42: 1462-1469
    PubMedGoogle Scholar
  • 47 Martin TJ, Allan EH, Fukumoto S. The plasminogen activator and inhibitor system in bone remodeling. Growth Regulation 1993; 3: 209-214
    PubMedGoogle Scholar
  • 48 Leloup G, Lemoine P, Carmeliet P, Vaes G. Bone resorption and response to parathyroid hormone or 1,25 dihyroxyvitamin D3 in fetal metatarsals and calvariae from transgenic mice devoid of tissue or urokinase type plasminogen activator or of their inhibitor, PAI-l. Twenty fourth European Symposium on Calcified Tissues. 05/1995. Aarhus; Denmark: Calcified Tissue International (Abstract)
    Google Scholar
  • 49 Bouillon R, Van Herck E, Verhaeghe J, Caimeliet P. Bone metabolism in transgenic mice, deficient in tissue type plasminogen activator. Xth International Congress on Calcium regulatory hormones. 02/1995. Melbourne; Australia: Bone and Mineral (Abstract)
    Google Scholar
  • 50 Friedman GC, Seeds NW. Tissue plasminogen activator expression in the embryonic nervous system. Des Brain PS 1994; 81: 41-49
    PubMedGoogle Scholar
  • 51 Sunni Y, Dent AR, Owen DE, Seeley PS, Morris RJ. The expression of tissue and urokinase plasminogen activator in neuronal development suggests different models of proteolytic involvement in neuronal growth. Development 1992; 116: 625-637
    PubMedGoogle Scholar
  • 52 Qian Z, Gilbert ME, Colicos MA, Kandel ER, Kuhl D. issue-type plasminogen activator is induced as an immediate-early gene during seizure, kindling and long-term potentiation. Nature 1993; 361: 453-457
    CrossrefPubMedGoogle Scholar
  • 53 Sappino AP, Madani R, Huarte J, Belin D, Kiss JZ, Wohlwend A, Vassalli JD. Extracellular proteolysis in the adult murine brain. J Clin Invest 1993; 92: 679-685
    CrossrefPubMedGoogle Scholar
  • 54 Krystosek A, Seeds NW. Plasminogen activator release at the neuronal growth cone. Sciencez 1981; 213: 1532-1534
    PubMedGoogle Scholar
  • 55 Carroll PM, Tsirka S, Richards WG, Frohman MA, Strickland S. Promoter sequences of the tissue-type plasminogen activator gene are able to confer tissue-specific expression of LacZ during mouse development (in press).
    PubMedGoogle Scholar
  • 56 Theuring F, Aguzzi A, Turner JD, Kropp C, Wohn KD, Hoffmann S, Schleuning WD. Analysis of human tissue-type plasminogen activator gene promoter activity during embiyogenesis of transgenic mice and rats and its induction in the adult mouse brain (submitted).
    PubMedGoogle Scholar
  • 57 Verrol S, Seeds NW. Characterization of l25I-tissue plasminogen activator binding to cerebellar granule neurons. J Cell Biol 1989; 109: 265-271
    CrossrefPubMedGoogle Scholar
  • 58 Kristensen P, Nielsen LS, Grpndahl-Jansen J, Andreasen PB, Larsson LI, Dano KI. J Cell Biol 1985; 101: 305-311
    CrossrefPubMed
  • 59 Dano K, Andreasen PA, Grondhal-Hansen J, Kristensen P, Nielsen LS, Skriver L. Plasminogen activators, tissue degradation and cancer. Adv Cancer Res 1985; 44: 139-266
    PubMedGoogle Scholar
  • 60 Pyke C, Kristensen P, Ralfkiaer E, Grondahl-Hansen J, Eriksen J, Blasi F, Dano K. Urokinase-type plasminogen activator is expressed in stromal cells and its receptor in cancer cells at invasive foci in human colon adenocarcinomas. Am J Pathol 1991; 138: 1059-1067
    PubMedGoogle Scholar
  • 61 Duffy MJ. Plasminogen activators and cancer. Blood Coagulation Fibrinolysis 1991; 1: 681-687
    PubMedGoogle Scholar
  • 62 Janicke F, Schmitt M, Graeff H. Clinical relevance of the urokinase-type and tissue-type plasminogen activators and of their type 1 inhibitor in breast cancer. Sem Thromb Hemostas 1991; 17: 303-312
    Article in Thieme ConnectPubMedGoogle Scholar
  • 63 Poggi A, Bellelli E, Carmela R, Castelli MP, Salvatore L, Marinacci R, Erickson LA, Benedetta Donati M, Bini A. Reduced pulmonary metastases of Lewis Lung Carcinoma in mice transgenic for the plasminogen activator inhibitor-1 gene (submitted).
    PubMedGoogle Scholar
  • 64 Wagner EF. On trasferring genes into stem cells and mice. Embo J 1990; 9: 3024-3032
    PubMedGoogle Scholar
  • 65 Botteri FM, Van der Putten H, Rajput B, Ballmer-Hofer K, Nagamine Y. Induction of the urokinase-type plasminogen activator gene by cytoskeleton- disrupting agents. In: Serine proteases and their serpin inhibitors in the nervous system.. Ed.: Festoff WB. Plenum Press; New York: 1990: 105-114
    Google Scholar
  • 66 Declerck P, Carmeliet P, Verstreken M, De Cock F, Collen D. Monoclonal antibodies raised against the targeted proteins in gene-inactivated mice (submitted).
    PubMedGoogle Scholar