© 2000 American Heart Association, Inc.
Cellular Biology |
Release of Active Tissue Factor by Human Arterial Smooth Muscle Cells
From the Cardiovascular Institute (A.D.S., M.R., J.T.F., E.A.F., M.B.T.), Division of Thrombosis Research (P.L.A.G., V.B., Y.N.), Division of Pulmonary Medicine (L.M.S.), Department of Medicine (A.D.S., B.S., M.R., P.L.A.G., V.B., J.T.F., E.A.F., L.M.S., Y.N., M.B.T.), and Department of Pathology (J.T.F.), Mount Sinai School of Medicine, New York, NY.
Correspondence to Mark B. Taubman, Mount Sinai School of Medicine, Box 1269, One Gustave L. Levy Place, New York, NY 10029. E-mail mark.taubman{at}mssm.edu
Abstract—Tissue factor (TF), the
initiator of coagulation, is thought to function predominantly at the
cell surface. Recent data have suggested that active TF is present
extracellularly in atherosclerotic plaques, the arterial
wall, and the blood. This study was conducted to determine whether
smooth muscle cells (SMCs), a major source of arterial TF,
could generate extracellular TF. Active TF accumulated in the medium of
cultured human SMCs, representing 
10% of that measured
in the underlying cells at 24 hours. Platelet-derived growth
factor, phorbol ester, and tumor necrosis factor-
caused 3-fold
increases in TF activity in the medium. Release of TF into the medium
was dependent on the presence of the TF transmembrane domain but not
the cytoplasmic domain. Antibodies to TF precipitated most of the
activity from the culture medium, whereas antibodies to the
ß1-integrin subunit precipitated 33% of the activity.
Treatment with detergent or
phosphatidylserine:phosphatidylcholine did not
increase activity, suggesting that all TF released by SMCs was in the
appropriate lipid milieu and not encrypted. Western blotting showed
that the medium contained full-length TF protein. Fluorescent
cytometry showed that extracellular TF was present largely in
particles 
200 nm, which had a density of 1.10 g/mL. We hypothesize
that active extracellular TF found in the injured arterial
wall and atherosclerotic plaques derives, in part, from SMC
microparticles. (Circ Res. 2000;87:126-132.)
Key Words: smooth muscle • tissue factor • thrombosis • microparticles
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