SEARCH:   Advanced

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Eitzman, D. T. Articles by Ginsburg, D. Search for Related Content PubMed PubMed Citation Articles by Eitzman, D. T. Articles by Ginsburg, D. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 December 2000, Vol. 96, No. 13, pp. 4212-4215 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Plasminogen activator inhibitor-1 deficiency protects against atherosclerosis progression in the mouse carotid artery Daniel T. Eitzman, Randal J. Westrick, Zuojun Xu, Julia Tyson, and David Ginsburg From the Divisions of Cardiology and Medical Genetics, Department of Internal Medicine, and the Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor, MI. Dissolution of the fibrin blood clot is regulated in large part by plasminogen activator inhibitor-1 (PAI-1). Elevated levels of plasma PAI-1 may be an important risk factor for atherosclerotic vascular disease and are associated with premature myocardial infarction. The role of the endogenous plasminogen activation system in limiting thrombus formation following atherosclerotic plaque disruption is unknown. This study found that genetic deficiency for PAI-1, the primary physiologic regulator of tissue-type plasminogen activator (tPA), prolonged the time to occlusive thrombosis following photochemical injury to carotid atherosclerotic plaque in apolipoprotein E-deficient (apoE/) mice. However, anatomic analysis revealed a striking difference in the extent of atherosclerosis at the carotid artery bifurcation between apoE/ mice and mice doubly deficient for apoE and PAI-1 (PAI-1//apoE/). Consistent with a previous report, PAI-1+/+/apoE/and PAI-1//apoE/ mice developed similar atherosclerosis in the aortic arch. The marked protection from atherosclerosis progression at the carotid bifurcation conferred by PAI-1 deficiency suggests a critical role for PAI-1 in the pathogenesis of atherosclerosis at sites of turbulent flow, potentially through the inhibition of fibrin clearance. Consistent with this hypothesis, intense fibrinogen/fibrin staining was observed in atherosclerotic lesions at the carotid bifurcation compared to the aortic arch. These observations identify significant differences in the pathogenesis of atherosclerosis at varying sites in the vascular tree and suggest a previously unappreciated role for the plasminogen activation system in atherosclerosis progression at sites of turbulent flow. © 2000 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. G. Camici, J. Steffel, I. Amanovic, A. Breitenstein, J. Baldinger, S. Keller, T. F. Luscher, and F. C. Tanner Rapamycin promotes arterial thrombosis in vivo: implications for everolimus and zotarolimus eluting stents Eur. Heart J., June 29, 2009; (2009) ehp259v1. [Abstract] [Full Text] [PDF] D. Peters, M. Kastantin, V. R. Kotamraju, P. P. Karmali, K. Gujraty, M. Tirrell, and E. Ruoslahti Targeting atherosclerosis by using modular, multifunctional micelles PNAS, June 16, 2009; 106(24): 9815 - 9819. [Abstract] [Full Text] [PDF] H. Liu, A. E Dear, L. B Knudsen, and R. W Simpson A long-acting glucagon-like peptide-1 analogue attenuates induction of plasminogen activator inhibitor type-1 and vascular adhesion molecules J. Endocrinol., April 1, 2009; 201(1): 59 - 66. [Abstract] [Full Text] [PDF] M. Drinane, J. Mollmark, L. Zagorchev, K. Moodie, B. Sun, A. Hall, S. Shipman, P. Morganelli, M. Simons, and M. J. Mulligan-Kehoe The Antiangiogenic Activity of rPAI-123 Inhibits Vasa Vasorum and Growth of Atherosclerotic Plaque Circ. Res., February 13, 2009; 104(3): 337 - 345. [Abstract] [Full Text] [PDF] C. C. Werneck, C. P. Vicente, J. S. Weinberg, A. Shifren, R. A. Pierce, T. J. Broekelmann, D. M. Tollefsen, and R. P. Mecham Mice lacking the extracellular matrix protein MAGP1 display delayed thrombotic occlusion following vessel injury Blood, April 15, 2008; 111(8): 4137 - 4144. [Abstract] [Full Text] [PDF] Y. Izuhara, S. Takahashi, M. Nangaku, S. Takizawa, H. Ishida, K. Kurokawa, C. van Ypersele de Strihou, N. Hirayama, and T. Miyata Inhibition of Plasminogen Activator Inhibitor-1: Its Mechanism and Effectiveness on Coagulation and Fibrosis Arterioscler Thromb Vasc Biol, April 1, 2008; 28(4): 672 - 677. [Abstract] [Full Text] [PDF] R. L.C. Hoo, W.S. Chow, M.H. Yau, A. Xu, A. W.K. Tso, H.F. Tse, C. H.Y. Fong, S. Tam, L. Chan, and K. S.L. Lam Adiponectin Mediates the Suppressive Effect of Rosiglitazone on Plasminogen Activator Inhibitor-1 Production Arterioscler Thromb Vasc Biol, December 1, 2007; 27(12): 2777 - 2782. [Abstract] [Full Text] [PDF] R. J. Westrick, M. E. Winn, and D. T. Eitzman Murine Models of Vascular Thrombosis Arterioscler Thromb Vasc Biol, October 1, 2007; 27(10): 2079 - 2093. [Abstract] [Full Text] [PDF] S. Thalmann and C. A. Meier Local adipose tissue depots as cardiovascular risk factors Cardiovasc Res, September 1, 2007; 75(4): 690 - 701. [Abstract] [Full Text] [PDF] W. P. Fay, N. Garg, and M. Sunkar Vascular Functions of the Plasminogen Activation System Arterioscler Thromb Vasc Biol, June 1, 2007; 27(6): 1231 - 1237. [Abstract] [Full Text] [PDF] L. Hu, L.S.M. Boesten, P. May, J. Herz, N. Bovenschen, M.V. Huisman, J.F.P. Berbee, L.M. Havekes, B.J.M. van Vlijmen, and J.T. Tamsma Macrophage Low-Density Lipoprotein Receptor-Related Protein Deficiency Enhances Atherosclerosis in ApoE/LDLR Double Knockout Mice Arterioscler Thromb Vasc Biol, December 1, 2006; 26(12): 2710 - 2715. [Abstract] [Full Text] [PDF] J. Wang, L. Yin, and M. A. Lazar The Orphan Nuclear Receptor Rev-erb{alpha} Regulates Circadian Expression of Plasminogen Activator Inhibitor Type 1 J. Biol. Chem., November 10, 2006; 281(45): 33842 - 33848. [Abstract] [Full Text] [PDF] G. G. Camici, J. Steffel, A. Akhmedov, N. Schafer, J. Baldinger, U. Schulz, K. Shojaati, C. M. Matter, Z. Yang, T. F. Luscher, et al. Dimethyl Sulfoxide Inhibits Tissue Factor Expression, Thrombus Formation, and Vascular Smooth Muscle Cell Activation: A Potential Treatment Strategy for Drug-Eluting Stents Circulation, October 3, 2006; 114(14): 1512 - 1521. [Abstract] [Full Text] [PDF] J. K. Hennan, H. Elokdah, M. Leal, A. Ji, G. S. Friedrichs, G. A. Morgan, R. E. Swillo, T. M. Antrilli, A. Hreha, and D. L. Crandall Evaluation of PAI-039 [{1-Benzyl-5-[4-(trifluoromethoxy)phenyl]-1H-indol-3-yl}(oxo)acetic Acid], a Novel Plasminogen Activator Inhibitor-1 Inhibitor, in a Canine Model of Coronary Artery Thrombosis J. Pharmacol. Exp. Ther., August 1, 2005; 314(2): 710 - 716. [Abstract] [Full Text] [PDF] K. Yamamoto, K. Takeshita, T. Kojima, J. Takamatsu, and H. Saito Aging and plasminogen activator inhibitor-1 (PAI-1) regulation: implication in the pathogenesis of thrombotic disorders in the elderly Cardiovasc Res, May 1, 2005; 66(2): 276 - 285. [Abstract] [Full Text] [PDF] D. T. Eitzman, R. J. Westrick, Y. Shen, P. F. Bodary, S. Gu, S. L. Manning, S. L. Dobies, and D. Ginsburg Homozygosity for Factor V Leiden Leads to Enhanced Thrombosis and Atherosclerosis in Mice Circulation, April 12, 2005; 111(14): 1822 - 1825. [Abstract] [Full Text] [PDF] C Roncal, J Orbe, J.A Rodriguez, M Belzunce, O Beloqui, J Diez, and J.A Paramo Influence of the 4G/5G PAI-1 genotype on angiotensin II-stimulated human endothelial cells and in patients with hypertension Cardiovasc Res, July 1, 2004; 63(1): 176 - 185. [Abstract] [Full Text] [PDF] S. M. S. Espirito Santo, N. M. M. Pires, L. S. M. Boesten, G. Gerritsen, N. Bovenschen, K. W. van Dijk, J. W. Jukema, H. M. G. Princen, A. Bensadoun, W.-P. Li, et al. Hepatic low-density lipoprotein receptor-related protein deficiency in mice increases atherosclerosis independent of plasma cholesterol Blood, May 15, 2004; 103(10): 3777 - 3782. [Abstract] [Full Text] [PDF] A. E. Cozen, H. Moriwaki, M. Kremen, M. B. DeYoung, H. L. Dichek, K. I. Slezicki, S. G. Young, M. Veniant, and D. A. Dichek Macrophage-Targeted Overexpression of Urokinase Causes Accelerated Atherosclerosis, Coronary Artery Occlusions, and Premature Death Circulation, May 4, 2004; 109(17): 2129 - 2135. [Abstract] [Full Text] [PDF] Z. Xu, R. D. Balsara, N. V. Gorlatova, D. A. Lawrence, F. J. Castellino, and V. A. Ploplis Conservation of Critical Functional Domains in Murine Plasminogen Activator Inhibitor-1 J. Biol. Chem., April 23, 2004; 279(17): 17914 - 17920. [Abstract] [Full Text] [PDF] N. Ishimori, R. Li, P. M. Kelmenson, R. Korstanje, K. A. Walsh, G. A. Churchill, K. Forsman-Semb, and B. Paigen Quantitative Trait Loci Analysis for Plasma HDL-Cholesterol Concentrations and Atherosclerosis Susceptibility Between Inbred Mouse Strains C57BL/6J and 129S1/SvImJ Arterioscler Thromb Vasc Biol, January 1, 2004; 24(1): 161 - 166. [Abstract] [Full Text] [PDF] M. Roest and J. D. Banga Editorial Comment-- Genetic Make-Up for Increased PAI-1 Expression Protects Against Stroke Stroke, December 1, 2003; 34(12): 2828 - 2829. [Full Text] [PDF] B. E. Sobel, D. J. Taatjes, and D. J. Schneider Intramural Plasminogen Activator Inhibitor Type-1 and Coronary Atherosclerosis Arterioscler Thromb Vasc Biol, November 1, 2003; 23(11): 1979 - 1989. [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] I. Bot, J. H. von der Thusen, M. M.P.C. Donners, A. Lucas, M. L. Fekkes, S. C.A. de Jager, J. Kuiper, M. J.A.P. Daemen, T. J.C. van Berkel, S. Heeneman, et al. Serine Protease Inhibitor Serp-1 Strongly Impairs Atherosclerotic Lesion Formation and Induces a Stable Plaque Phenotype in ApoE-/- Mice Circ. Res., September 5, 2003; 93(5): 464 - 471. [Abstract] [Full Text] [PDF] M.-C. Alessi, D. Bastelica, A. Mavri, P. Morange, B. Berthet, M. Grino, and I. Juhan-Vague Plasma PAI-1 Levels Are More Strongly Related to Liver Steatosis Than to Adipose Tissue Accumulation Arterioscler Thromb Vasc Biol, July 1, 2003; 23(7): 1262 - 1268. [Abstract] [Full Text] [PDF] C. J. Lyon, R. E. Law, and W. A. Hsueh Minireview: Adiposity, Inflammation, and Atherogenesis Endocrinology, June 1, 2003; 144(6): 2195 - 2200. [Abstract] [Full Text] [PDF] N. V. Gorlatova, H. Elokdah, K. Fan, D. L. Crandall, and D. A. Lawrence Mapping of a Conformational Epitope on Plasminogen Activator Inhibitor-1 by Random Mutagenesis. IMPLICATIONS FOR SERPIN FUNCTION J. Biol. Chem., April 25, 2003; 278(18): 16329 - 16335. [Abstract] [Full Text] [PDF] A. T. Askari, M.-L. Brennan, X. Zhou, J. Drinko, A. Morehead, J. D. Thomas, E. J. Topol, S. L. Hazen, and M. S. Penn Myeloperoxidase and Plasminogen Activator Inhibitor 1 Play a Central Role in Ventricular Remodeling after Myocardial Infarction J. Exp. Med., March 3, 2003; 197(5): 615 - 624. [Abstract] [Full Text] [PDF] S. Devaraj, D. Y. Xu, and I. Jialal C-Reactive Protein Increases Plasminogen Activator Inhibitor-1 Expression and Activity in Human Aortic Endothelial Cells: Implications for the Metabolic Syndrome and Atherothrombosis Circulation, January 28, 2003; 107(3): 398 - 404. [Abstract] [Full Text] [PDF] V. de Waard, E. K. Arkenbout, P. Carmeliet, V. Lindner, and H. Pannekoek Plasminogen Activator Inhibitor 1 and Vitronectin Protect Against Stenosis in a Murine Carotid Artery Ligation Model Arterioscler Thromb Vasc Biol, December 1, 2002; 22(12): 1978 - 1983. [Abstract] [Full Text] [PDF] T. Kaneko, S. Fujii, A. Matsumoto, D. Goto, N. Ishimori, K. Watano, T. Furumoto, T. Sugawara, B. E. Sobel, and A. Kitabatake Induction of Plasminogen Activator Inhibitor-1 in Endothelial Cells by Basic Fibroblast Growth Factor and Its Modulation by Fibric Acid Arterioscler Thromb Vasc Biol, May 1, 2002; 22(5): 855 - 860. [Abstract] [Full Text] [PDF] A. Luttun, F. Lupu, E. Storkebaum, M. F. Hoylaerts, L. Moons, J. Crawley, F. Bono, A. R. Poole, P. Tipping, J.-M. Herbert, et al. Lack of Plasminogen Activator Inhibitor-1 Promotes Growth and Abnormal Matrix Remodeling of Advanced Atherosclerotic Plaques in Apolipoprotein E-Deficient Mice Arterioscler Thromb Vasc Biol, March 1, 2002; 22(3): 499 - 505. [Abstract] [Full Text] [PDF] A. Braun, B. L. Trigatti, M. J. Post, K. Sato, M. Simons, J. M. Edelberg, R. D. Rosenberg, M. Schrenzel, and M. Krieger Loss of SR-BI Expression Leads to the Early Onset of Occlusive Atherosclerotic Coronary Artery Disease, Spontaneous Myocardial Infarctions, Severe Cardiac Dysfunction, and Premature Death in Apolipoprotein E-Deficient Mice Circ. Res., February 22, 2002; 90(3): 270 - 276. [Abstract] [Full Text] [PDF] J. C.Y. Chan, D. A. Duszczyszyn, F. J. Castellino, and V. A. Ploplis Accelerated Skin Wound Healing in Plasminogen Activator Inhibitor-1-Deficient Mice Am. J. Pathol., November 1, 2001; 159(5): 1681 - 1688. [Abstract] [Full Text] [PDF] R. J. Westrick, P. F. Bodary, Z. Xu, Y.-C. Shen, G. J. Broze, and D. T. Eitzman Deficiency of Tissue Factor Pathway Inhibitor Promotes Atherosclerosis and Thrombosis in Mice Circulation, June 26, 2001; 103(25): 3044 - 3046. [Abstract] [Full Text] [PDF] Y. Zhu, P. M. Farrehi, and W. P. Fay Plasminogen Activator Inhibitor Type 1 Enhances Neointima Formation After Oxidative Vascular Injury in Atherosclerosis-Prone Mice Circulation, June 26, 2001; 103(25): 3105 - 3110. [Abstract] [Full Text] [PDF] A. Braun, B. L. Trigatti, M. J. Post, K. Sato, M. Simons, J. M. Edelberg, R. D. Rosenberg, M. Schrenzel, and M. Krieger Loss of SR-BI Expression Leads to the Early Onset of Occlusive Atherosclerotic Coronary Artery Disease, Spontaneous Myocardial Infarctions, Severe Cardiac Dysfunction, and Premature Death in Apolipoprotein E-Deficient Mice Circ. Res., February 22, 2002; 90(3): 270 - 276. [Abstract] [Full Text] [PDF] D. T. Eitzman, R. J. Westrick, X. Bi, S. L. Manning, J. E. Wilkinson, G. J. Broze, and D. Ginsburg Lethal Perinatal Thrombosis in Mice Resulting From the Interaction of Tissue Factor Pathway Inhibitor Deficiency and Factor V Leiden Circulation, May 7, 2002; 105(18): 2139 - 2142. [Abstract] [Full Text] [PDF]

	Copyright © 2000 by American Society of Hematology         Online ISSN: 1528-0020