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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:218.)
© 2002 American Heart Association, Inc.

Vascular Biology

Expression and Localization of Tissue Factor Pathway Inhibitor-2 in Normal and Atherosclerotic Human Vessels

James T.B. Crawley; David A. Goulding; Valérie Ferreira; Nicholas J. Severs; Florea Lupu

From the Thrombosis Research Institute (J.T.B.C., D.A.G., F.L.), London, England; the Oklahoma Medical Research Foundation (J.T.B.C., F.L.), Oklahoma City, Oklahoma; the Center for Molecular Microbiology (D.A.G.), Imperial College, London, England; the Academic Medical Center (V.F.), University of Amsterdam, Amsterdam, Netherlands; and the National Heart and Lung Institute (N.J.S.), Imperial College, London, England.

Reprint requests to Dr Florea Lupu, Oklahoma Medical Research Foundation, Cardiovascular Biology Research Program, Acree-Woodworth Research Building, 825 NE 13th St, Oklahoma City, OK 73104. E-mail florea-lupu{at}omrf.ouhsc.edu

Tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type, serine protease inhibitor with inhibitory activity toward activated factor XI, plasma kallikrein, plasmin, certain matrix metalloproteinases, and the tissue factor:activated factor VII complex. In this study, we investigated TFPI-2 expression and localization in normal and atherosclerotic human arteries by using in situ hybridization and immunohistochemical techniques. In healthy human blood vessels, TFPI-2 was detected in the vascular endothelium alone. In human atherosclerotic tissues, TFPI-2 expression was assigned to macrophages, T cells, endothelial cells, and smooth muscle cells. Western blot analysis for TFPI-2 confirmed its production by cultured human aortic smooth muscle cells, U937 cells (monocytes), and Jurkat (T cell) cell lines. Reverse transcription–polymerase chain reaction revealed similar TFPI-2 expression levels in both monocytes and macrophages in culture. Electron microscopic study with immunogold labeling revealed the association of TFPI-2 antigen with both the extracellular matrix and plasma membranes. TFPI-2 antigen was detected in some areas of atheroma that also stained positively for both tissue factor and factor VII. Moreover, detection of TFPI-2 in close spatial proximity to plasmin/plasminogen on macrophages, on endothelial cells, and in matrix-rich areas highlighted its possible functional significance in the regulation of plasmin activity and downstream proteolytic mechanisms that occur in the atherosclerotic lesion.

Key Words: atherosclerosis • matrix metalloproteinases • tissue factor pathway inhibitor-2 • plasmin • tissue factor

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