Arteriosclerosis, Thrombosis, and Vascular Biology. 1996;16:539-545
© 1996 American Heart Association, Inc.
Articles |
Inhibitors of Fibrinolysis Are Elevated in Atherosclerotic Plaque
From the Department of Medicine and Therapeutics (L.A.R., B.B.), the Department of Molecular and Cell Biology (L.A.R., N.A.B.), and the Department of Pathology (P.A.J.B.), University of Aberdeen, Scotland, UK.
Correspondence to Dr L. A. Robbie, Department of Medicine and Therapeutics, University of Aberdeen, Foresterhill, Aberdeen AB9 2ZD, Scotland, UK. E-mail larobbie@abdn.ac.uk.
Abstract The proteins of the fibrinolytic system have been
examined in the human normal and atherosclerotic arterial
wall by immunohistochemical techniques and by quantitative immunoassay
of extracts. The concentration of plasminogen
activator inhibitor-1 (PAI-1) increased
significantly during the progression from normal vessels to fatty
streaks to the developed atherosclerotic plaque. Staining for PAI-1 was
strongly positive, particularly in the areas adjacent to the plaque. In
these areas, PAI-1 appeared to be colocalized with its binding protein
vitronectin. 
2-Antiplasmin
(2-AP) was present in the aorta at even higher
concentrations than PAI-1; a small but significant increase was seen in
some atherosclerotic compared with normal vessel walls. Tissue
plasminogen activator (TPA) showed the opposite
trend, being lowest in lesions with plaque. Thus, higher concentrations
of the two principal inhibitors of
fibrinolysis, PAI-1 and 2-AP, together
with lower levels of TPA, are characteristic of advanced
atheromatous lesions. Alteration in the balance of the
fibrinolytic system, favoring its inhibition, may predispose to the
development or maintenance of atherosclerotic plaque.
Key Words: atherosclerosis • fibrinolysis • PAI-1 • 2-AP
This article has been cited by other articles:
 |
|
 |
|
  K. Quinn, M. Henriques, T. Parker, A. S. Slutsky, and H. Zhang Human neutrophil peptides: a novel potential mediator of inflammatory cardiovascular diseases Am J Physiol Heart Circ Physiol, November 1, 2008; 295(5): H1817 - H1824. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. V. Gorlatova, J. M. Cale, H. Elokdah, D. Li, K. Fan, M. Warnock, D. L. Crandall, and D. A. Lawrence Mechanism of Inactivation of Plasminogen Activator Inhibitor-1 by a Small Molecule Inhibitor J. Biol. Chem., March 23, 2007; 282(12): 9288 - 9296. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. G. Nielsen, J. P. Crow, F. Zhou, and D. A. Parks Peroxynitrite Inactivates Tissue Plasminogen Activator Anesth. Analg., May 1, 2004; 98(5): 1312 - 1317. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Schafer, K. Muller, A. Hecke, E. Mounier, J. Goebel, D. J. Loskutoff, and S. Konstantinides Enhanced Thrombosis in Atherosclerosis-Prone Mice Is Associated With Increased Arterial Expression of Plasminogen Activator Inhibitor-1 Arterioscler Thromb Vasc Biol, November 1, 2003; 23(11): 2097 - 2103. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Konstantinides, K. Schafer, and D. J. Loskutoff Do PAI-1 and Vitronectin Promote or Inhibit Neointima Formation?: The Exact Role of the Fibrinolytic System in Vascular Remodeling Remains Uncertain Arterioscler Thromb Vasc Biol, December 1, 2002; 22(12): 1943 - 1945. [Full Text] [PDF]
|
|
|
|
 |
|
 T. Hryszko, J. Malyszko, J. S. Malyszko, S. Brzosko, K. Pawlak, and M. Mysliwiec A possible role of thrombin-activatable fibrinolysis inhibitor in disturbances of fibrinolytic system in renal transplant recipients Nephrol. Dial. Transplant., August 1, 2001; 16(8): 1692 - 1696. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Sironi, A. M. Calvio, L. Arnaboldi, A. Corsini, A. Parolari, M. de Gasparo, E. Tremoli, and L. Mussoni Effect of Valsartan on Angiotensin II-Induced Plasminogen Activator Inhibitor-1 Biosynthesis in Arterial Smooth Muscle Cells Hypertension, March 1, 2001; 37(3): 961 - 966. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Orbe, J. A Rodriguez, A. Calvo, A. Grau, M. S Belzunce, D. Martinez-Caro, and J. A Paramo Vitamins C and E attenuate plasminogen activator inhibitor-1 (PAI-1) expression in a hypercholesterolemic porcine model of angioplasty Cardiovasc Res, February 1, 2001; 49(2): 484 - 492. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. H. A. Quax, M. L. M. Lamfers, J. H. P. Lardenoye, J. M. Grimbergen, M. R. de Vries, J. Slomp, M. C. de Ruiter, M. M. Kockx, J. H. Verheijen, and V. W. M. van Hinsbergh Adenoviral Expression of a Urokinase Receptor-Targeted Protease Inhibitor Inhibits Neointima Formation in Murine and Human Blood Vessels Circulation, January 30, 2001; 103(4): 562 - 569. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Konstantinides, K. Schafer, T. Thinnes, and D. J. Loskutoff Plasminogen Activator Inhibitor-1 and Its Cofactor Vitronectin Stabilize Arterial Thrombi After Vascular Injury in Mice Circulation, January 30, 2001; 103(4): 576 - 583. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. A. Ploplis, I. Cornelissen, M. J. Sandoval-Cooper, L. Weeks, F. A. Noria, and F. J. Castellino Remodeling of the Vessel Wall after Copper-Induced Injury Is Highly Attenuated in Mice with a Total Deficiency of Plasminogen Activator Inhibitor-1 Am. J. Pathol., January 1, 2001; 158(1): 107 - 117. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Uchiyama, M. Kurabayashi, Y. Ohyama, T. Utsugi, N. Akuzawa, M. Sato, S. Tomono, S. Kawazu, and R. Nagai Hypoxia Induces Transcription of the Plasminogen Activator Inhibitor-1 Gene Through Genistein-Sensitive Tyrosine Kinase Pathways in Vascular Endothelial Cells Arterioscler Thromb Vasc Biol, April 1, 2000; 20(4): 1155 - 1161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Lopez, F. Peiretti, B. Bonardo, I. Juhan-Vague, and G. Nalbone Tumor Necrosis Factor alpha Up-regulates in an Autocrine Manner the Synthesis of Plasminogen Activator Inhibitor Type-1 during Induction of Monocytic Differentiation of Human HL-60 Leukemia Cells J. Biol. Chem., February 4, 2000; 275(5): 3081 - 3087. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Bourcier and P. Libby HMG CoA Reductase Inhibitors Reduce Plasminogen Activator Inhibitor-1 Expression by Human Vascular Smooth Muscle and Endothelial Cells Arterioscler Thromb Vasc Biol, February 1, 2000; 20(2): 556 - 562. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kietzmann, U. Roth, and K. Jungermann Induction of the Plasminogen Activator Inhibitor-1 Gene Expression by Mild Hypoxia Via a Hypoxia Response Element Binding the Hypoxia-Inducible Factor-1 in Rat Hepatocytes Blood, December 15, 1999; 94(12): 4177 - 4185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. M. Lang, K. M. Moser, and R. R. Schleef Elevated Expression of Urokinase-like Plasminogen Activator and Plasminogen Activator Inhibitor Type 1 During the Vascular Remodeling Associated With Pulmonary Thromboembolism Arterioscler Thromb Vasc Biol, May 1, 1998; 18(5): 808 - 815. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-Q. Chen, M. Su, R. R. Walia, Q. Hao, J. W. Covington, and D. E. Vaughan Sp1 Sites Mediate Activation of the Plasminogen Activator Inhibitor-1 Promoter by Glucose in Vascular Smooth Muscle Cells J. Biol. Chem., April 3, 1998; 273(14): 8225 - 8231. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Tomiyama, Y. Kimura, H. Mitsuhashi, T. Kinouchi, H. Yoshida, T. Kushiro, and N. Doba Relationship Between Endothelial Function and Fibrinolysis in Early Hypertension Hypertension, January 1, 1998; 31(1): 321 - 327. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Kanse, O. Benzakour, C. Kanthou, C. Kost, H. R. Lijnen, and K. T. Preissner Induction of Vascular SMC Proliferation by Urokinase Indicates a Novel Mechanism of Action in Vasoproliferative Disorders Arterioscler Thromb Vasc Biol, November 1, 1997; 17(11): 2848 - 2854. [Abstract] [Full Text]
|
|
|
|
|
|
T. Padro, M. Steins, C.-X. Li, R. M Mesters, D. Hammel, H. H Scheld, and J. Kienast Comparative analysis of plasminogen activator inhibitor-1 expression in different types of atherosclerotic lesions in coronary arteries from human heart explants Cardiovasc Res, October 1, 1997; 36(1): 28 - 36. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Kauhanen, V. Siren, O. Carpen, A. Vaheri, M. Lepantalo, and R. Lassila Plasminogen Activator Inhibitor-1 in Neointima of Vein Grafts : Its Role in Reduced Fibrinolytic Potential and Graft Failure Circulation, September 16, 1997; 96(6): 1783 - 1789. [Abstract] [Full Text]
|
|
|
|
|
|
T. J. Podor, S. G. Shaughnessy, M. N. Blackburn, and C. B. Peterson New Insights into the Size and Stoichiometry of the Plasminogen Activator Inhibitor Type-1{middle dot}Vitronectin Complex J. Biol. Chem., August 11, 2000; 275(33): 25402 - 25410. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Stefansson, E. Petitclerc, M. K. K. Wong, G. A. McMahon, P. C. Brooks, and D. A. Lawrence Inhibition of Angiogenesis in Vivo by Plasminogen Activator Inhibitor-1 J. Biol. Chem., March 9, 2001; 276(11): 8135 - 8141. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-Y. Zhang, I. Ishii, and H. S. Kruth Plasmin-mediated Macrophage Reversal of Low Density Lipoprotein Aggregation J. Biol. Chem., October 13, 2000; 275(42): 33176 - 33183. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Gorlach, I. Diebold, V. B. Schini-Kerth, U. Berchner-Pfannschmidt, U. Roth, R. P. Brandes, T. Kietzmann, and R. Busse Thrombin Activates the Hypoxia-Inducible Factor-1 Signaling Pathway in Vascular Smooth Muscle Cells : Role of the p22phox-Containing NADPH Oxidase Circ. Res., July 6, 2001; 89(1): 47 - 54. [Abstract] [Full Text] [PDF]
|
|