From the Divisions of Cardiovascular Diseases (N.M.C.) and Biochemistry
and Molecular Biology, Molecular Medicine Program, Mayo Clinic and Foundation,
Rochester, Minn.
Correspondence to Robert D. Simari, MD, 200 1st Street SW, Rochester, MN 55904. E-mail simari.robert{at}mayo.edu
Background—Plaque disruption and
exposure of subendothelial procoagulants such as tissue
factor (TF) to circulating factor VII/VIIa (FVII/VIIa) lead to
intravascular thrombosis. Tissue factor pathway inhibitor
(TFPI) is an endogenous inhibitor of TF-induced
coagulation that binds to factor Xa and the TF-FVIIa catalytic complex
in a two-step process. The aim of this study was to determine the
expression of TFPI within human atherosclerotic plaque and its role in
modulation of TF activity.
Methods and Results—We measured the level of TFPI antigen in
human carotid plaque and determined the relationship between TFPI and
TF activity within plaque. Furthermore, we examined the biological
activity and immunolocalization patterns of TFPI within carotid plaque.
TFPI was detectable (TFPI+ group) in 22 of 34 specimens (mean±SEM,
404.4±91.8 pg/mg) and undetectable (TFPI- group) in 12 of 34
specimens. In the TFPI- group, normalized TF activity was
significantly greater than that in the TFPI+ group (0.28±0.04 vs
0.14±0.02 U/pg, P=0.002). Furthermore, neutralization
of TFPI activity using a polyclonal antibody resulted in an 8-fold
increase in TF activity in the TFPI+ group (P=0.001) but
had no effect in the TFPI- group. Immunostaining for
TFPI showed localization to endothelial cells, vascular
smooth muscle cells within the fibrous cap region of the plaque, and
macrophages within the shoulder region of the plaque.
Conclusions—Taken together, these data suggest that biologically
active TFPI is present within human atherosclerotic plaque and is
associated with attenuated TF activity.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Presence of Tissue Factor Pathway Inhibitor in Human Atherosclerotic Plaques Is Associated With Reduced Tissue Factor Activity
Key Words: atherosclerosis • tissue factor • inhibitor • plaque
This article has been cited by other articles:
 |
|
 |
|
  M. Jayachandran, A. Sanzo, W. G. Owen, and V. M. Miller Estrogenic regulation of tissue factor and tissue factor pathway inhibitor in platelets Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H1908 - H1916. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Fisher, A. Paganini-Hill, A. Martin, M. Cosgrove, J. F. Toole, H. J.M. Barnett, and J. Norris Carotid Plaque Pathology: Thrombosis, Ulceration, and Stroke Pathogenesis Stroke, February 1, 2005; 36(2): 253 - 257. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.E. Morange, C. Simon, M.C. Alessi, G. Luc, D. Arveiler, J. Ferrieres, P. Amouyel, A. Evans, P. Ducimetiere, I. Juhan-Vague, et al. Endothelial Cell Markers and the Risk of Coronary Heart Disease: The Prospective Epidemiological Study of Myocardial Infarction (PRIME) Study Circulation, March 23, 2004; 109(11): 1343 - 1348. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. W. Kopp, T. Holzenbein, S. Steiner, R. Marculescu, H. Bergmeister, D. Seidinger, I. Mosberger, C. Kaun, M. Cejna, R. Horvat, et al. Inhibition of restenosis by tissue factor pathway inhibitor: in vivo and in vitro evidence for suppressed monocyte chemoattraction and reduced gelatinolytic activity Blood, March 1, 2004; 103(5): 1653 - 1661. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. R. Bijsterveld, A. H. Moons, J. C. M. Meijers, M. Levi, H. R. Buller, and R. J. G. Peters The impact on coagulation of an intravenous loading dose in addition to a subcutaneousregimen of low-molecular-weight heparinin the initial treatment of acute coronary syndromes J. Am. Coll. Cardiol., August 6, 2003; 42(3): 424 - 427. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. M. Caplice, T. J. Bunch, P. G. Stalboerger, S. Wang, D. Simper, D. V. Miller, S. J. Russell, M. R. Litzow, and W. D. Edwards Smooth muscle cells in human coronary atherosclerosis can originate from cells administered at marrow transplantation PNAS, April 15, 2003; 100(8): 4754 - 4759. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Yin, C. Yutani, Y. Ikeda, K. Enjyoji, H. Ishibashi-Ueda, S. Yasuda, Y. Tsukamoto, H. Nonogi, Y. Kaneda, and H. Kato Tissue factor pathway inhibitor gene delivery using HVJ-AVE liposomes markedly reduces restenosis in atherosclerotic arteries Cardiovasc Res, December 1, 2002; 56(3): 454 - 463. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kato Regulation of Functions of Vascular Wall Cells by Tissue Factor Pathway Inhibitor: Basic and Clinical Aspects Arterioscler. Thromb. Vasc. Biol., April 1, 2002; 22(4): 539 - 548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H.M Moons, M. Levi, and R. J.G Peters Tissue factor and coronary artery disease Cardiovasc Res, February 1, 2002; 53(2): 313 - 325. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. K. Shah Reduced Tissue Factor Pathway Inhibitor-1 After Pharmacological Thrombolysis: An Epiphenomenon or Potential Culprit in Rethrombosis? Circulation, January 22, 2002; 105(3): 270 - 271. [Full Text] [PDF]
|
|
|
|
|
|
I. Ott, V. Malcouvier, A. Schomig, and F.-J. Neumann Proteolysis of Tissue Factor Pathway Inhibitor-1 by Thrombolysis in Acute Myocardial Infarction Circulation, January 22, 2002; 105(3): 279 - 281. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. M. Caplice, C. Panetta, T. E. Peterson, L. S. Kleppe, C. S. Mueske, G. M. Kostner, G. J. Broze Jr, and R. D. Simari Lipoprotein (a) binds and inactivates tissue factor pathway inhibitor: a novel link between lipoproteins and thrombosis Blood, November 15, 2001; 98(10): 2980 - 2987. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Jander, M. Sitzer, A. Wendt, M. Schroeter, M. Buchkremer, M. Siebler, W. Muller, W. Sandmann, and G. Stoll Expression of Tissue Factor in High-Grade Carotid Artery Stenosis : Association With Plaque Destabilization Stroke, April 1, 2001; 32(4): 850 - 854. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Schecter, B. Spirn, M. Rossikhina, P. L. A. Giesen, V. Bogdanov, J. T. Fallon, E. A. Fisher, L. M. Schnapp, Y. Nemerson, and M. B. Taubman Release of Active Tissue Factor by Human Arterial Smooth Muscle Cells Circ. Res., July 21, 2000; 87(2): 126 - 132. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Crawley, F. Lupu, A. D. Westmuckett, N. J. Severs, V. V. Kakkar, and C. Lupu Expression, Localization, and Activity of Tissue Factor Pathway Inhibitor in Normal and Atherosclerotic Human Vessels Arterioscler. Thromb. Vasc. Biol., May 1, 2000; 20(5): 1362 - 1373. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Zoldhelyi, J. McNatt, H. S. Shelat, Y. Yamamoto, Z.-Q. Chen, and J. T. Willerson Thromboresistance of Balloon-Injured Porcine Carotid Arteries After Local Gene Transfer of Human Tissue Factor Pathway Inhibitor Circulation, January 25, 2000; 101(3): 289 - 295. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Schonbeck, F. Mach, G. K. Sukhova, M. Herman, P. Graber, M. R. Kehry, and P. Libby CD40 Ligation Induces Tissue Factor Expression in Human Vascular Smooth Muscle Cells Am. J. Pathol., January 1, 2000; 156(1): 7 - 14. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Soejima, H. Ogawa, H. Yasue, K. Kaikita, K. Takazoe, K. Nishiyama, K. Misumi, S. Miyamoto, M. Yoshimura, K. Kugiyama, et al. Angiotensin-converting enzyme inhibition reduces monocyte chemoattractant protein-1 and tissue factor levels in patients with myocardial infarction J. Am. Coll. Cardiol., October 1, 1999; 34(4): 983 - 988. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Soejima, H. Ogawa, H. Yasue, K. Kaikita, K. Nishiyama, K. Misumi, K. Takazoe, Y. Miyao, M. Yoshimura, K. Kugiyama, et al. Heightened Tissue Factor Associated With Tissue Factor Pathway Inhibitor and Prognosis in Patients With Unstable Angina Circulation, June 8, 1999; 99(22): 2908 - 2913. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Singh, S. Pan, C. S. Mueske, T. Witt, L. S. Kleppe, T. E. Peterson, A. Slobodova, J.-Y. Chang, N. M. Caplice, and R. D. Simari Role for Tissue Factor Pathway in Murine Model of Vascular Remodeling Circ. Res., July 6, 2001; 89(1): 71 - 76. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kato Regulation of Functions of Vascular Wall Cells by Tissue Factor Pathway Inhibitor: Basic and Clinical Aspects Arterioscler. Thromb. Vasc. Biol., April 1, 2002; 22(4): 539 - 548. [Abstract] [Full Text] [PDF]
|
|