| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
American Journal of Pathology, Vol 143, 875-885, Copyright © 1993 by American Society for Investigative Pathology
REGULAR ARTICLES |
PG Tipping, P Davenport, M Gallicchio, EL Filonzi, J Apostolopoulos and J Wojta
Department of Medicine (Monash Medical Centre), Monash University, Clayton, Victoria, Australia.
The capacity of macrophages to influence directly and indirectly fibrinolytic processes in atherosclerosis was studied using macrophages isolated from atherosclerotic plaques of patients undergoing surgical repair of distal aortic and femoral arteries. These cells were characterized by their morphology, adherence, esterase positivity, and expression of CD14 antigen. Production of plasminogen activator inhibitor type-1 (PAI-1) by plaque macrophages (6.7 +/- 2.7 ng/10(5) cells/24 hours [mean +/- SEM]) was significantly greater than PAI-1 production by blood monocytes isolated simultaneously from the same patients (1.8 +/- 1.5 ng/10(5) cells/24 hours). Production of tissue type plasminogen activator and urokinase type was not augmented compared to blood monocytes. Conditioned medium from cultured plaque macrophages significantly increased production of PAI-1 by endothelial cells (85 +/- 11% above basal) and vascular smooth muscle cells (25 +/- 10%) in vitro. This response was significantly greater than the response to monocyte-conditioned medium (endothelial cells 38 +/- 11%, vascular smooth muscle cells 2.5 +/- 2.0%). Stimulation of endothelial cell PAI-1 production by macrophage-conditioned medium was partially inhibitable by a monoclonal antibody to transforming growth factor- beta. Tissue type plasminogen activator production by endothelial cells and vascular smooth muscle cells was not affected by plaque macrophage- or monocyte-conditioned medium. Urokinase type plasminogen activator production by endothelial cells and vascular smooth muscle cells was undetectable in control medium and was augmented to similar levels in response to plaque macrophage- and monocyte-conditioned media. These results demonstrate upregulation of PAI-1 production by macrophages in atheromatous plaques and the capacity of soluble products from plaque macrophages to upregulate PAI-1 production by endothelial cells and vascular smooth muscle cells in vitro. These data suggest that macrophages in atherosclerotic plaques may inhibit thrombolysis both directly and indirectly by effects of their soluble products on endothelial cells and vascular smooth muscle cells.
This article has been cited by other articles:
 |
|
 |
|
  E. M. Kairuz, M. N. Barber, C. R. Anderson, M. Kanagasundaram, G. R. Drummond, and R. L. Woods C-type natriuretic peptide (CNP) suppresses plasminogen activator inhibitor-1 (PAI-1) in vivo Cardiovasc Res, June 1, 2005; 66(3): 574 - 582. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Brogren, L. Karlsson, M. Andersson, L. Wang, D. Erlinge, and S. Jern Platelets synthesize large amounts of active plasminogen activator inhibitor 1 Blood, December 15, 2004; 104(13): 3943 - 3948. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. A. Hsueh and D. Bruemmer Peroxisome Proliferator-Activated Receptor {gamma}: Implications for Cardiovascular Disease Hypertension, February 1, 2004; 43(2): 297 - 305. [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]
|
|
|
|
 |
|
 E. W. RAINES, H. KOYAMA, and N. O. CARRAGHER The Extracellular Matrix Dynamically Regulates Smooth Muscle Cell Responsiveness to PDGF Ann. N.Y. Acad. Sci., May 1, 2000; 902(1): 39 - 52. [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]
|
|
|
|
 |
|
 B. E. Sobel Increased Plasminogen Activator Inhibitor-1 and Vasculopathy : A Reconcilable Paradox Circulation, May 18, 1999; 99(19): 2496 - 2498. [Full Text] [PDF]
|
|
|
|
|
|
A. M. Thogersen, J.-H. Jansson, K. Boman, T. K. Nilsson, L. Weinehall, F. Huhtasaari, and G. Hallmans High Plasminogen Activator Inhibitor and Tissue Plasminogen Activator Levels in Plasma Precede a First Acute Myocardial Infarction in Both Men and Women : Evidence for the Fibrinolytic System as an Independent Primary Risk Factor Circulation, November 24, 1998; 98(21): 2241 - 2247. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Geppert, S. Graf, R. Beckmann, S. Hornykewycz, E. Schuster, B. R. Binder, and K. Huber Concentration of Endogenous tPA Antigen in Coronary Artery Disease : Relation to Thrombotic Events, Aspirin Treatment, Hyperlipidemia, and Multivessel Disease Arterioscler. Thromb. Vasc. Biol., October 1, 1998; 18(10): 1634 - 1642. [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]
|
|
|
|
|
|
G. Christ, P. Hufnagl, C. Kaun, G. Mundigler, G. Laufer, K. Huber, J. Wojta, and B. R. Binder Antifibrinolytic Properties of the Vascular Wall: Dependence on the History of Smooth Muscle Cell Doublings In Vitro and In Vivo Arterioscler. Thromb. Vasc. Biol., April 1, 1997; 17(4): 723 - 730. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. M. Schwartz, D. deBlois, and E. R. M. O'Brien The Intima : Soil for Atherosclerosis and Restenosis Circ. Res., September 1, 1995; 77(3): 445 - 465. [Full Text]
|
|
|
|
|
|
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]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
