© 1998 American Heart Association, Inc.
Vascular Biology |
Expression of Tissue Factor Pathway Inhibitor in Vascular Smooth Muscle Cells and Its Regulation by Growth Factors
From the Divisions of Cardiovascular Diseases and Biochemistry and Molecular Biology (N.M.C., C.S.M., L.S.K., T.E.P., R.D.S.), Molecular Medicine Program, Mayo Clinic and Foundation, Rochester, Minn; and the Department of Medicine, Washington University Medical Center (G.J.B.), St. Louis, Mo.
Correspondence to Robert D. Simari, MD, 200 1st St SW, Rochester, MN 55904. E-mail simari.robert{at}mayo.edu
Abstract—Tissue factor
pathway inhibitor (TFPI) in vivo is thought to be
synthesized mainly by endothelial cells. To date, no
significant regulator of TFPI synthesis has been described. Vascular
smooth muscle cells (VSMC) express tissue factor in vitro and in vivo,
which may contribute to vascular thrombosis. We hypothesized that VSMC
might also express TFPI. To determine this, we examined growth-arrested
coronary VSMC in culture and found that VSMC secreted an amount
of TFPI similar to that seen in endothelial cells.
Immunohistochemistry of normal human coronary arteries showed
TFPI staining throughout the media and intima of the vessel with
localization to VSMC and endothelial cells. To
determine regulation of TFPI expression in VSMC, we examined the
effects of serum stimulation on TFPI secretion and found that FBS
induced a 5-fold increase in TFPI antigen and activity levels in
conditioned medium at 48 hours (P<0.001) when compared
with serum-free conditions. A similar stimulatory effect was seen with
10% pooled human serum. Moreover, epidermal growth factor and
platelet-derived growth factor-B increased TFPI secretion by 4- to
5-fold and 2- to 3-fold, respectively (P<0.05), and
these growth factors accounted for 
50% of the TFPI secretion
effects of human serum. The serum effect was associated with a 3-fold
increase in TFPI mRNA 24 hours after release from growth arrest and a
50% decrease in TFPI secretion after treatment with actinomycin D.
Taken together, this study suggests that there is significant TFPI
expression in VSMC in culture and in VSMC within the intima and media
of the normal coronary artery wall. We present the first
evidence for TFPI regulation by serum in VSMC and more specifically by
its constituent growth factors, epidermal growth factor and
platelet-derived growth factor-B.
Key Words: tissue factor • inhibitor • smooth muscle • regulation
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