This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Konstantinides, S. Articles by Loskutoff, D. J. Search for Related Content PubMed PubMed Citation Articles by Konstantinides, S. Articles by Loskutoff, D. J. Related Collections Genetically altered mice Smooth muscle proliferation and differentiation Arterial thrombosis Fibrinogen/fibrin Thrombin

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1943.)
© 2002 American Heart Association, Inc.

Editorial

Do PAI-1 and Vitronectin Promote or Inhibit Neointima Formation?

The Exact Role of the Fibrinolytic System in Vascular Remodeling Remains Uncertain

Stavros Konstantinides; Katrin Schäfer; David J. Loskutoff

From the Department of Cardiology and Pulmonary Medicine (S.K., K.S.), Georg August University of Goettingen, Germany; and Department of Cell Biology (D.J.L.), Division of Vascular Biology, The Scripps Research Institute, La Jolla, Calif.

Correspondence to David J. Loskutoff, PhD, The Scripps Research Institute, Department of Cell Biology, Division of Vascular Biology, 10550 North Torrey Pines Rd, VB3, La Jolla, CA 92037. E-mail loskutof@scripps.edu

An extract of the first 250 words of the full text is provided, because this article has no abstract.

In this issue of Arteriosclerosis, Thrombosis and Vascular Biology, de Waard et al¹ report enhanced neointima formation and luminal stenosis following carotid artery ligation in mice deficient for plasminogen activator inhibitor-1 (PAI-1) or vitronectin (VN) compared with their wild-type counterparts. Their findings appear to contradict those of a recently published study by Peng et al,² thus adding fuel to the ongoing discussion and growing uncertainty about the exact role of PAI-1 and VN in the vascular remodeling process underlying atherosclerosis and restenosis. In this brief editorial, we review the evidence that suggests that PAI-1 and VN should influence this process, and then we attempt to reconcile the two publications.

See page 1978

Interest in the involvement of the fibrinolytic system, and particularly PAI-1, in the development and complications of human atherosclerosis was sparked by several clinical studies which reported elevated plasma concentrations of the inhibitor in patients with acute coronary syndromes.^3–5 In addition, histological observations consistently demonstrated that PAI-1 gene expression was upregulated in macrophages and smooth muscle cells (SMCs) present in human atherosclerotic lesions^6–8 and in lesions that develop in animal models of atherosclerosis.^9,10 Finally, inflammatory proatherosclerotic mediators, including oxidized LDL, were shown to upregulate the expression of PAI-1 in endothelial cells and vascular SMCs in culture.^11–13 Taken together, these observations implicate PAI-1 in the pathology of the vessel wall that develops in response to vascular insult.

As the principal physiological inhibitor of plasminogen activation, PAI-1 would seem to play a key role in the regulation of vascular . . . [Full Text of this Article]

This article has been cited by other articles:

				M. Blumenstein, R. Prakash, G. J. S. Cooper, R. A. North, and SCOPE Consortium Aberrant Processing of Plasma Vitronectin and High-Molecular-Weight Kininogen Precedes the Onset of Preeclampsia Reproductive Sciences, December 1, 2009; 16(12): 1144 - 1152. [Abstract] [PDF]

				G. Otsuka, A. Stempien-Otero, A. D. Frutkin, and D. A. Dichek Mechanisms of TGF-{beta}1-Induced Intimal Growth: Plasminogen-Independent Activities of Plasminogen Activator Inhibitor-1 and Heterogeneous Origin of Intimal Cells Circ. Res., May 11, 2007; 100(9): 1300 - 1307. [Abstract] [Full Text] [PDF]

				J. Sainz and M. Sata Maintenance of Vascular Homeostasis by Bone Marrow-Derived Cells. Arterioscler Thromb Vasc Biol, June 1, 2006; 26(6): 1196 - 1197. [Full Text] [PDF]

				K. Schafer, M. R. Schroeter, C. Dellas, M. Puls, M. Nitsche, E. Weiss, G. Hasenfuss, and S. V. Konstantinides Plasminogen Activator Inhibitor-1 From Bone Marrow-Derived Cells Suppresses Neointimal Formation After Vascular Injury in Mice Arterioscler Thromb Vasc Biol, June 1, 2006; 26(6): 1254 - 1259. [Abstract] [Full Text] [PDF]

				G. Otsuka, R. Agah, A. D. Frutkin, T. N. Wight, and D. A. Dichek Transforming Growth Factor Beta 1 Induces Neointima Formation Through Plasminogen Activator Inhibitor-1-Dependent Pathways Arterioscler Thromb Vasc Biol, April 1, 2006; 26(4): 737 - 743. [Abstract] [Full Text] [PDF]

				Y.-P. Wu, H. J. Bloemendal, E. E. Voest, T. Logtenberg, P. G. de Groot, M. F. B. G. Gebbink, and H. C. de Boer Fibrin-incorporated vitronectin is involved in platelet adhesion and thrombus formation through homotypic interactions with platelet-associated vitronectin Blood, August 15, 2004; 104(4): 1034 - 1041. [Abstract] [Full Text] [PDF]

				M. Pynn, K. Schafer, S. Konstantinides, and M. Halle Exercise Training Reduces Neointimal Growth and Stabilizes Vascular Lesions Developing After Injury in Apolipoprotein E-Deficient Mice Circulation, January 27, 2004; 109(3): 386 - 392. [Abstract] [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]

				R. N. Hasan, S. Phukan, and S. Harada Differential Regulation of Early Growth Response Gene-1 Expression by Insulin and Glucose in Vascular Endothelial Cells Arterioscler Thromb Vasc Biol, June 1, 2003; 23(6): 988 - 993. [Abstract] [Full Text] [PDF]