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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. 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