Circulation. 1997;96:3555-3560
(Circulation. 1997;96:3555-3560.)
© 1997 American Heart Association, Inc.
Primate Smooth Muscle Cell Migration From Aortic Explants Is Mediated by Endogenous Platelet-Derived Growth Factor and Basic Fibroblast Growth Factor Acting Through Matrix Metalloproteinases 2 and 9
R. D. Kenagy, PhD;
C. E. Hart, PhD;
W. G. Stetler-Stevenson, MD, PhD;
;
A. W. Clowes, MD
From the Department of Surgery, University of Washington (R.D.K.,
A.W.C.), and Zymogenetics, Inc, Seattle, Wash (C.E.H.), and Laboratory of
Pathology, Division of Clinical Sciences, National Cancer Institute, Bethesda,
Md (W.G.S.-S.).
Correspondence to Richard Kenagy, PhD, University of Washington School of Medicine, Department of Surgery, Box 356410, 1959 NE Pacific St, Seattle, Wash 98195-6410. E-mail rkenagy{at}u.washington.edu
 |
Abstract
|
|---|
Background Migration of arterial smooth muscle
cells (SMCs)
is regulated by basic fibroblast growth factor (bFGF),
platelet-derived
growth factor (PDGF), and matrix
metalloproteinases (MMPs) in
the injured rat carotid artery. We have
recently shown that
migration of SMCs from baboon aortic explants
depends on the
activity of MMPs, but the identity of the stimulatory
MMPs and
the role of bFGF and PDGF in this primate system are not
known.
Methods and Results These experiments were designed to determine
whether MMP2, MMP9, bFGF, or PDGF plays a role in SMC migration from
medial explants of baboon aorta. Explants were cultured in serum-free
medium with insulin, transferrin, and ovalbumin. Neutralizing
antibodies to MMP2 and antibodies that inhibit activation of proMMP9
decreased SMC migration from the aortic explants. Antibodies to bFGF
and to the
- and ß-subunits of the PDGF receptor also inhibited
migration from the explants. Addition of bFGF and PDGF-BB but not
PDGF-AA increased migration. The antibodies to bFGF but not the
antibodies to the PDGF receptor subunits decreased the levels of MMP9,
whereas all the antibodies decreased activated MMP2.
Conclusions These data demonstrate that SMC migration from
primate aortic explants is dependent on endogenous MMP2,
MMP9, PDGF, and bFGF. The data also suggest that PDGF-induced (PDGF-BB
or possibly PDGF-AB) migration is dependent on MMP2, whereas
bFGF-induced migration depends on both MMP2 and MMP9.
Key Words: atherosclerosis metalloproteinases muscle, smooth platelet-derived factors tissue
 |
Introduction
|
|---|
Smooth
muscle cell migration, an important factor in the development
and
pathophysiology of blood vessels,
1,2 is regulated
in vitro
by various proteinases, cytokines, and growth
factors.
36 In the balloon-injured rat carotid
artery, the correlation of
changes in plasminogen
activators
79 and
MMPs
10,11 with
SMC migration has suggested a role
for plasminogen activators
and MMPs. The
inhibition of SMC migration in vivo in the rat
by treatment with the
plasminogen inhibitor tranexamic
acid
8 and MMP
inhibitors
11,12 supports these
conclusions. In addition,
endogenous
bFGF
13 and PDGF
8 have been
clearly shown to stimulate
SMC migration from the media to the
developing neointima.
We recently developed a primate model of migration, because the
observations in the rat might not be relevant for
humans.1419 We have demonstrated that urokinase
plasminogen activator, tissue
plasminogen activator, and an unidentified MMP
are needed for primate SMC migration in baboon aortic
explants.20 In this report, we demonstrate the
importance of MMP2, MMP9, bFGF, and PDGF in the migration of SMCs out
of baboon aortic explants.
 |
Methods
|
|---|
Reagents and supplies were purchased from Sigma Chemical Co
unless
indicated otherwise. Electrophoresis supplies were from BioRad
and
National Diagnostics. bFGF and rabbit anti-human bFGF
were obtained
from R&D Systems. The anti-bFGF at 2 µg/mL
neutralizes
50% of the bioactivity of 0.5 to 1.5 ng bFGF/mL and has no
activity
against acidic fibroblast growth factor. Recombinant PDGF-BB
was
purified as described previously.
21
Monoclonal antibodies to
the PDGF-

(169.3.1.1.1) and PDGF-ß
(163.3.1.1.1) receptors
were produced as previously
described.
22,23 Antibodies to MMP9
(66B and
711C) were generously provided by Deborah
French, Naomi
Ramos-DeSimone, and James Quigley.
24 These
antibodies
do not cross-react with other MMPs. IgG was purified from
rabbit
antiserum to MMP2 (Ab IVase
25) by protein
A affinity chromatography
(Pierce). This antibody has
been used previously to specifically
inhibit the activity of MMP2 in
SMCs and in HT-1080 cells.
26,27 Normal rabbit IgG
(R&D Systems, Inc) and a monoclonal antibody
against bovine liver
carboxylase (an IgG1; No. 170.3.1; Zymogenetics
Inc) were used as
control antibodies.
Explants were prepared from baboon thoracic aortas as previously
described.20 After the
endothelial layer was removed, the inner media was
dissected from the adventitia and chopped into
1-mm2 pieces. Explants were then distributed to
25-cm2 tissue culture flasks (15 per flask) in
DMEM with 5 µg transferrin/mL, 6 µg insulin/mL, 1 mg
ovalbumin/mL, and any test factors. Explants were examined
daily and counted as positive for migration if one or more cells were
observed on the plastic culture surface. This method of quantification
precludes any involvement of proliferation of cells outside of the
explants. In some experiments, the number of migrating cells per
explant was determined at day 7.
Gelatin zymography for MMPs was performed as described
previously28 on medium harvested on day 7.
Because the DNA content per flask20 was not
altered by any treatment (data not presented), equal volumes of
medium were loaded per lane. Explants from each flask were extracted in
200 µL of 2 mol/L guanidine HCl, 0.2% Triton X-100, 10
mmol/L CaCl2, and 50 mmol/L
Tris (pH 7.5) with a Teflon pestle in a 1.5-mL microfuge tube. The
extract was dialyzed overnight against 500 to 1000 volumes of 50
mmol/L Tris/0.2% Triton X-100 (pH 7.4) twice. Equal amounts of
protein were loaded per lane for extracts of explants. Bands were
quantified by scanning of gels with an HP3C Deskscan (Hewlett Packard)
and analyzed with NIH Imagequant software. MMP2 and MMP9,
purified as complexes of tissue inhibitor of
metalloproteinases 2 and 1, respectively, were used as standards (a
gift from H.G. Welgus, Washington University, St Louis, Mo)
Analysis of results was performed with the
Wilcoxon signed-rank test (SPSS/PC+). The Bonferroni correction
was used for multiple comparisons. In the experiments designed to test
whether PDGF-AA altered the stimulatory effect of PDGF-BB, results were
analyzed by repeated-measures ANOVA (SPSS/PC+). Explant
experiments were done with single or multiple flasks for each condition
with explants from a single animal. All values are the mean±SEM of the
indicated number of animals.
 |
Results
|
|---|
Role of MMP2 and MMP9 in SMC Migration
Because MMP activity is needed for migration of SMCs from baboon
aortic
explants and MMP2 and MMP9 are the major MMPs we have
detected,
20 we tested the effect of antibodies to
MMP2 and MMP9 on migration.
We have previously observed that SMCs
migrate out of the explants
at a steady rate after a lag of 3 days.
Approximately 50% of
explants exhibit migrating SMCs at day 7, and
>90% are positive
by day 10.
20 The antibody to
MMP2 blocked migration dose-dependently
(Fig 1A

). The antibodies to MMP9, which
inhibit the activation
of proMMP9,
24 also
decreased the rate of SMC migration but to
a lesser extent (Fig 1B

).

View larger version (19K):
[in this window]
[in a new window]
|
Figure 1. Role of MMP2 and MMP9 in SMC migration.
Results are expressed as % of control migration at day 7. A, Effect of
anti-MMP2 (solid bars) or rabbit IgG (open bars). n=9 or 10 for 25 to
150 µg/mL and 4 for 200 µg/mL; *P<.05. On average,
9 or 10 of 15 explants were positive for migration for control groups
of 25, 150, and 200 µg/mL, and for 50 µg/mL, 7 of 15 control
explants were positive. B, Antibodies to MMP9 (66B and 711C) and an
irrelevant IgG1 were used at 40 µg/mL. On average, 7 of 15 control
explants were positive. n=5 to 9; *P<.05.
|
|
Role of bFGF and PDGF in SMC Migration
To determine whether endogenous bFGF and PDGF
stimulate migration of SMCs in primate arterial tissue as
is observed in the rat, we studied the effects of blocking antibodies
to bFGF and the PDGF receptor subunits. Addition of antibodies to bFGF
decreased migration by 50% at day 7 (Fig 2
). Antibodies to the
- and ß-chains
of the PDGF receptor each decreased migration by 30%. A mixture of
anti
- and antiß-antibodies at 25 µg/mL each did
not inhibit SMC migration from explants to any greater extent than
either antibody alone at 50 µg/mL (Fig 2
). These
concentrations were chosen to be greater than the maximally
inhibitory concentrations on the basis of previous studies
in which the anti
-chain antibody (2.5 µg/mL) inhibited
PDGF-AA (100%) and PDGF-BB (80%) mediated mitogenesis in baboon
SMCs.22 The antiß-chain antibody does not
block PDGF-AAmediated mitogenesis because PDGF-AA activates
only the PDGF
-receptor. The antibody does block 50% of
PDGF-BBmediated baboon SMC mitogenesis at 5 µg/mL and up to
60% at higher concentrations.22

View larger version (20K):
[in this window]
[in a new window]
|
Figure 2. Effect of antibodies to bFGF at 100 µg/mL and to
- and ß-chains of PDGF receptor at 50 µg/mL individually or
combined at 25 µg/mL each on migration as % of control migration
(*P<.05; n=9 to 13; on average, 8 of 15 control
explants had migrating cells on day 7).
|
|
The addition of either PDGF-BB or bFGF stimulated migration of SMCs
from the explants at day 7 (Fig 3A
). The
relative effect of bFGF and PDGF-BB was greater at earlier times when
control migration was low (eg, at day 5, migration with bFGF and
PDGF-BB, each at 50 ng/mL, was 269±51% and 343±64% of
control, respectively, when
4 of 15 control explants had migrating
cells; n=19). Qualitatively similar results were observed when the
number of cells migrating from explants was counted (Fig 3B
), although
this form of quantification includes migration and proliferation of
cells on the plastic. In contrast to PDGF-BB, PDGF-AA (50 ng/mL)
did not significantly alter migration, nor did it alter the effect of
PDGF-BB when added with PDGF-BB (Fig 4
).

View larger version (19K):
[in this window]
[in a new window]
|
Figure 3. Dose-response effects of bFGF (open bars) and
PDGF-BB (solid bars) on migration at day 7. A, Migration measured as %
of explants showing migrating cells and expressed as % of control
values (*P<.05 vs control; n=7 to 19). On average, 9 of
15 control explants showed migrating cells. B, Effects on number of
migrating cells per explant expressed as % control values
(*P<.05 vs control; n=7 to 13). Number of cells per
explant in control explants was 8.5±2.8 (mean±SEM; n=13).
|
|

View larger version (27K):
[in this window]
[in a new window]
|
Figure 4. Time course of effects of PDGF-BB, PDGF-AA, or both
together (each at 50 ng/mL) on SMC migration (as % of
migration-positive explants; n=6). By repeated-measures ANOVA, PDGF-AA
neither had an effect of its own nor did it affect stimulatory action
of PDGF-BB.
|
|
Effects of bFGF and PDGF on MMP2 and MMP9
Because MMP2, MMP9, bFGF, and PDGF activity are required for SMC
migration in this model, we performed gelatin zymography to determine
whether bFGF or PDGF might act by increasing either of the MMPs.
Addition of 50 ng/mL bFGF increased levels of MMP9 and 60-kD
MMP2 (activated MMP2) by >60%, whereas 50 ng/mL
PDGF-BB had no significant effect on either (Figs 5A
and 6
).
The antibody to bFGF decreased levels of MMP9 by 45% and the
activated 60-kD form of MMP2 by 36% (Figs 5B
and 6
).
Antibodies to the PDGF receptor subunits had no effect on MMP9 but
decreased levels of the 60-kD MMP2 by 52% (Figs 5B
and 6
). Levels of
proMMP2 (70-kD) were not changed by any of the treatments (data not
presented).

View larger version (51K):
[in this window]
[in a new window]
|
Figure 5. Gelatin zymograms of 7-day conditioned medium after
treatment with (A) 50 ng/mL bFGF or PDGF-BB or with (B) anti-PDGF
receptor- plus anti-PDGF receptor-ß (25 µg/mL each or a control
IgG1at 50 µg/mL) or anti-bFGF (or a control rabbit IgG [RbIgG] at
100 µg/mL).
|
|

View larger version (14K):
[in this window]
[in a new window]
|
Figure 6. Levels of MMP9 (A) and 60-kD MMP2 (B) by
densitometric scanning of gelatin zymograms of explant conditioned
medium. Explants were treated with anti-bFGF (100 µg/mL; n=5 to 6)
antibodies to - and ß-chains of PDGF receptor (a combination of 25
µg/mL each; n=5; *P<.05 vs IgG control) or 50 ng/mL
of either bFGF or PDGF-BB (n=10 to 20; *P<.05 vs
control). Results (mean±SEM) are presented as % of control or
% of appropriate IgG control.
|
|
 |
Discussion
|
|---|
The migration of vascular SMCs plays an important role in the
production
of the thickened intima after vascular
injury
29 and also in
the neovascularization that
occurs during wound healing, ischemia,
and the formation of
advanced atherosclerotic plaques.
3032 Less is
known about the regulation of SMC migration in vascular
tissue of
primate origin compared with the vascular tissue of
other experimental
animals. For example, SMC migration from
human restenotic
arterial tissue is faster than from primary
atherosclerotic
tissue or undiseased tissue.
3335 We and
others
have previously shown that a general MMP inhibitor blocks
migration
in the injured rat carotid artery
12,36
and also in baboon aortic
explants.
20 We have now
identified MMP2 and MMP9 as MMPs that
mediate primate SMC migration
through native matrix. MMP2 and
MMP9 have been shown to be involved in
the invasion through
matrix of various other cell
types,
37 including
cytotrophoblasts,
38 fibrosarcoma
cells,
27 glioblastoma
cells,
39 U937 cells,
40 and
T
cells.
41 Rat SMCs have been shown to require
MMP2 to invade
Matrigel in vitro.
26 MMP activity
is required for migration
in vitro only when SMCs migrate through
matrix 1,
12,26 indicating
that it is the ability
of the MMP2 and MMP9 to degrade one or
more of their described
substrates (including collagens I, III,
IV, V, and XI, gelatins I and
V, and elastin
4245) that
increases
migration.
MMP2 and MMP9 are secreted as inactive proenzymes that must be
activated by cleavage of the N-terminal prosegment. How the
MMPs are being activated in the explants is not known. MMP2 can
be activated by the membrane-type
MMPs,46,47 whereas binding to
Vß3
integrin48 may promote autoactivation. Whether
membrane-type MMPs and
Vß3 are expressed in
the normal baboon artery or after injury is not known. MMP9 can be
activated by MMP3, cathepsin G, tissue kallikrein, MMP2, and
high concentrations of plasmin.42,4952 The
antibodies 66B and 711C, which inhibited SMC migration from
explants, inhibit activation by MMP2, MMP3, and tissue kallikrein
(N. Ramos-deSimone, PhD, and J. Quigley, PhD, personal communication,
1997).
Our observation that migration of SMCs through explants is stimulated
by endogenous PDGF and bFGF confirms in a primate model the
results obtained in the balloon-injured rat carotid
artery.8,13,53 The inhibition of migration with
antibodies to the PDGF receptor subunits was only partial, because in
some experiments, antibodies were completely depleted by 7 days.
However, there was a significant negative correlation between migration
and the concentration of antibodies (R.D.K., C.E.H., A.W.C.,
unpublished data). PDGF might also be involved in the formation of a
"neointima" in cultured human saphenous
veins.54 These observations support the
conclusion reached in the rat experiments that a major effect of PDGF
in arterial tissue is to stimulate cell migration. In
addition, our results suggest that part of the stimulatory effect on
migration caused by bFGF or by PDGF is mediated by MMP2 and MMP9. The
induction of MMP9 that occurs after arterial injury in the
baboon20 and rat10,11 may
be at least partly caused by bFGF released from injured
SMCs.55,56 It is of interest that cultured rat,
baboon (R.D. Kenagy, N. Zempo, and A.W. Clowes, unpublished data), and
human SMCs57 do not make MMP9 constitutively or
in response to either bFGF or PDGF. These observations are
consistent with reports that SMCs on plastic respond
differently than when in matrix58 and that
passaged SMCs are different from primary SMCs.59
In addition, induction of MMP9 might depend on activation by several
growth factors
simultaneously.60,61
Because PDGF-BB but not PDGF-AA stimulates migration of SMCs from
explants, it is likely that the BB (or possibly AB) isoform of PDGF is
active in the explants. This is supported by the inhibitory
effects on SMC migration of antibodies against the
- and ß-PDGF
receptor subunits, because only PDGF-B chain can bind to both
subunits.62 PDGF-BB but not PDGF-AA also
stimulates migration of cultured baboon SMCs.22
We have previously reported that PDGF-AA can inhibit PDGF-BBmediated
chemotaxis but not chemokinesis of SMCs in
vitro.22 The lack of an effect of PDGF-AA on
PDGF-BBmediated migration from explants may be because a chemotactic
gradient might not be present in this system. Our results are also
consistent with the observation that injury induces
PDGF-Bchain expression in rat,64
rabbit,65 and human66
arteries. This leaves the role of PDGF-A chain, which is also induced
after arterial injury,6668 less
clear. The expression of PDGF-A does not correlate with proliferation
in vivo,69 even though PDGF-A chain mediates
proliferation in vitro.7073
The use of primate models is attractive compared with the commonly used
rat model because of differences between rats and humans and the
similarities between nonhuman primates and humans with regard to
vascular responses. We have demonstrated similar responses in the
injured baboon artery and arterial explants for SMC entry
into the S phase and production of urokinase
plasminogen activator and
MMP9.20 Arterial explants may prove
to be a promising model of arterial injury, which is
difficult to study in primates, particularly in humans.
 |
Selected Abbreviations and Acronyms
|
|---|
| bFGF |
= |
basic fibroblast growth factor |
| MMP |
= |
matrix metalloproteinase |
| PDGF |
= |
platelet-derived growth factor |
| SMC |
= |
smooth muscle cell |
|
 |
Acknowledgments
|
|---|
This work was supported by grants from the National Institutes
of
Health (HL-30946, HL-18645, and RR-00166). Our thanks to Randolph
Geary,
MD, Thomas R. Kirkman, Larry Kraiss, MD, Sandro Lepidi, MD,
Erney
Mattsen, MD, and Selina Vergel for procuring aortic specimens;
to
Debra Gilbertson for anti-PDGF receptor antibody generation;
and to
Kitty Ratcliff and Holly Lea for technical assistance.
We also thank
Deborah French, Naomi Ramos-DeSimone, and James
Quigley for their
advice and for providing the antibodies to
MMP9.
 |
Footnotes
|
|---|
Presented in part in abstract form at Experimental Biology 93,
March 28April 1, 1993, New Orleans, La (
FASEB J. 1993;7:A637)
and the Meeting of ASBMB, AAIP, and AAI, June 26, 1996,
New Orleans, La (
FASEB J. 1996;10:A1297).
Received May 6, 1997;
revision received August 6, 1997;
accepted August 13, 1997.
 |
References
|
|---|
-
Schwartz SM, Heimark RL, Majesky MW. Developmental
mechanisms underlying pathology of arteries. Physiol
Rev. 1990;70:11771210.[Abstract/Free Full Text]
-
Ross R. The pathogenesis of
atherosclerosis: a perspective for the 1990s.
Nature. 1993;362:801809.[Medline]
[Order article via Infotrieve]
-
Sato Y, Hamanaka R, Ono J, Kuwano M, Rifkin DB, Takaki
R. The stimulatory effect of PDGF on vascular smooth muscle cell
migration is mediated by the induction of endogenous basic
FGF. Biochem Biophys Res Commun. 1991;174:12601266.[Medline]
[Order article via Infotrieve]
-
Bell L, Madri JA. Effect of platelet factors on
migration of cultured bovine aortic endothelial and
smooth muscle cells. Circ Res. 1989;65:10571065.[Abstract/Free Full Text]
-
Koyama N, Koshikawa T, Morisaki N, Saito Y, Yoshida S.
Bifunctional effects of transforming growth factor-ß on
migration of cultured rat aortic smooth muscle cells. Biochem
Biophys Res Commun. 1990;169:725729.[Medline]
[Order article via Infotrieve]
-
Higashiyama S, Abraham JA, Klagsbrun M.
Heparin-binding EGF-like growth factor stimulation of smooth muscle
cell migration: dependence on interactions with cell surface heparan
sulfate. J Cell Biol. 1993;122:933940.[Abstract/Free Full Text]
-
Clowes AW, Clowes MM, Au YPT, Reidy MA, Belin D.
Smooth muscle cells express urokinase during mitogenesis and
tissue-type plasminogen activator during
migration in injured rat carotid artery. Circ Res. 1990;67:6167.[Abstract/Free Full Text]
-
Jackson CL, Raines EW, Ross R, Reidy MA. Role of
endogenous platelet-derived growth factor in
arterial smooth muscle cell migration after balloon
catheter injury. Arterioscler Thromb. 1993;13:12181226.[Abstract/Free Full Text]
-
Reidy MA, Irvin C, Lindner V. Migration of
arterial wall cells: expression of plasminogen
activators and inhibitors in injured rat
arteries. Circ Res. 1996;78:405414.[Abstract/Free Full Text]
-
Zempo N, Kenagy RD, Au YPT, Bendeck M, Clowes MM, Reidy
MA, Clowes AW. Matrix metalloproteinases of vascular wall cells are
increased in balloon-injured rat carotid artery. J Vasc
Surg. 1994;20:209217.[Medline]
[Order article via Infotrieve]
-
Bendeck MP, Zempo N, Clowes AW, Galardy RE, Reidy MA.
Smooth muscle cell migration and matrix metalloproteinase expression
after arterial injury in the rat. Circ Res. 1994;75:539545.[Abstract/Free Full Text]
-
Zempo N, Koyama N, Kenagy RD, Lea HJ, Clowes AW.
Regulation of vascular smooth muscle cell migration and proliferation
in vitro and in injured rat arteries by a synthetic matrix
metalloproteinase inhibitor. Arterioscler Thromb Vasc
Biol. 1996;16:2833.[Abstract/Free Full Text]
-
Jackson CL, Reidy MA. Basic fibroblast growth factor:
its role in the control of smooth muscle cell migration. Am
J Pathol. 1993;143:10241031.[Abstract]
-
MERCATOR Study Group. Does the new
angiotensin converting enzyme inhibitor
cilazapril prevent restenosis after
percutaneous transluminal coronary angioplasty?
Results of the MERCATOR study: a multicenter, randomized, double-blind
placebo-controlled trial. Circulation. 1992;86:100110.[Abstract/Free Full Text]
-
Pepine CJ. Angiotensin converting enzyme
inhibition and coronary artery disease. J
Hypertens. 1994;12:565571.
-
Powell JS, Clozel JP, Muller RKM, Kuhn H, Hefti F,
Hosang M, Baumgartner HR. Inhibitors of
angiotensin-converting enzyme prevent myointimal
proliferation after vascular injury. Science. 1989;245:186188.[Abstract/Free Full Text]
-
Hanson SR, Powell JS, Dodson T, Lumsden A, Kelly AB,
Anderson JS, Clowes AW, Harker LA. Effects of angiotensin
converting enzyme inhibition with cilazapril on intimal hyperplasia in
injured arteries and vascular grafts in the baboon.
Hypertension. 1991;18(suppl II):II-70-II-76.
-
Geary RL, Koyama N, Wang TW, Vergel S, Clowes AW.
Failure of heparin to inhibit intimal hyperplasia in injured baboon
arteries: the role of heparin-sensitive and insensitive pathways in the
stimulation of smooth muscle cell migration and proliferation.
Circulation. 1995;91:29722981.[Abstract/Free Full Text]
-
Clowes AW, Clowes MM, Kirkman TR, Jackson CL, Au YPT,
Kenagy R. Heparin inhibits the expression of tissue-type
plasminogen activator by smooth muscle cells in
injured rat carotid artery. Circ Res. 1992;70:11281136.[Abstract/Free Full Text]
-
Kenagy RD, Vergel S, Mattsson E, Bendeck M, Reidy MA,
Clowes AW. The role of plasminogen, plasminogen
activators, and matrix metalloproteinases in primate
arterial smooth muscle cell migration. Arterioscler
Thromb Vasc Biol. 1996;16:13731382.[Abstract/Free Full Text]
-
Kelly JD, Raines EW, Ross R, Murray MJ. The B chain of
PDGF alone is sufficient for mitogenesis. EMBO J. 1985;4:33993405.[Medline]
[Order article via Infotrieve]
-
Koyama N, Hart CE, Clowes AW. Different functions of
the platelet-derived growth factor-
and -ß receptors for
the migration and proliferation of cultured baboon smooth muscle cells.
Circ Res. 1994;75:682691.[Abstract/Free Full Text]
-
Tiesman J, Hart CE. Identification of a soluble
receptor for platelet-derived growth factor in cell-conditioned
medium and human plasma. J Biol Chem. 1993;268:96219628.[Abstract/Free Full Text]
-
Ramos-DeSimone N, Moll UM, Quigley JP, French DL.
Inhibition of matrix metalloproteinase 9 activation by a specific
monoclonal antibody. Hybridoma. 1993;12:349363.[Medline]
[Order article via Infotrieve]
-
Brown PD, Levy AT, Margulies IMK, Liotta LA,
Stetler-Stevenson WG. Independent expression and cellular processing of
Mr 72,000 type IV collagenase
and interstitial collagenase in human
tumorigenic cell lines. Cancer Res. 1990;50:61846191.[Abstract/Free Full Text]
-
Pauly RR, Passaniti A, Bilato C, Monticone R, Cheng L,
Papadopoulos N, Gluzband YA, Smith L, Weinstein C, Lakatta EG, Crow MT.
Migration of cultured vascular smooth muscle cells through a basement
membrane barrier requires type IV collagenase activity and
is inhibited by cellular differentiation. Circ Res. 1994;75:4154.[Abstract/Free Full Text]
-
Albini A, Melchiori A, Santi L, Liotta LA, Brown PD,
Stetler-Stevenson WG. Tumor cell invasion inhibited by TIMP-2.
J Natl Cancer Inst. 1991;83:775779.[Abstract/Free Full Text]
-
Kenagy RD, Nikkari ST, Welgus HG, Clowes AW. Heparin
inhibits the induction of three matrix metalloproteinases (stromelysin,
92-kD gelatinase, and collagenase) in primate
arterial smooth muscle cells. J Clin
Invest. 1994;93:19871993.
-
Clowes AW, Schwartz SM. Significance of quiescent
smooth muscle migration in the injured rat carotid artery. Circ
Res. 1985;56:139145.[Abstract/Free Full Text]
-
Clark RAF. Mechanisms of cutaneous wound repair. In:
Fitzpatrick TB, Elsen AZ, Wolff K, Freedberg IM, Austen KF,
eds. Dermatology in General Medicine. 4th ed. New York, NY;
1993:473486.
-
White FC, Carroll SM, Magnet A, Bloor CM. Coronary
collateral development in swine after coronary artery occlusion.
Circ Res.. 1992;71:1490-1500.[Abstract/Free Full Text]
-
Zhang Y, Cliff WJ, Schoefl GI, Higgins G.
Immunohistochemical study of intimal microvessels in coronary
atherosclerosis. Am J Pathol. 1993;143:164172.[Abstract]
-
Pickering JG, Weir L, Rosenfield K, Stetz J, Jekanowski
J, Isner JM. Smooth muscle cell outgrowth from human atherosclerotic
plaque: implications for the assessment of lesion biology. J
Am Coll Cardiol. 1992;20:14301439.[Abstract]
-
Bauriedel G, Windstetter U, DeMaio SJ, Kandolf R,
Hofling B. Migratory activity of human smooth muscle cells cultivated
from coronary and peripheral primary and
restenotic lesions removed by percutaneous
atherectomy. Circulation. 1992;85:554564.[Abstract/Free Full Text]
-
Escaned J, de Jong M, Violaris AG, MacLeod DC, Umans
VA, van Suylen RJ, de Feyter PJ, Verdouw PD, Serruys PW. Clinical and
histological determinants of smooth-muscle cell outgrowth in cultured
atherectomy specimens: importance of thrombus organization. Coron
Artery Dis.. 1993;4:883890.[Medline]
[Order article via Infotrieve]
-
Bendeck MP, Irvin C, Reidy MA. Inhibition of matrix
metalloproteinase activity inhibits smooth muscle cell migration but
not neointimal thickening after arterial
injury. Circ Res. 1996;78:3843.[Abstract/Free Full Text]
-
MacDougall JR, Matrisian LM. Contributions of tumor and
stromal matrix metalloproteinases to tumor progression, invasion and
metastasis. Cancer Metast Rev. 1995;14:351362.[Medline]
[Order article via Infotrieve]
-
Librach CL, Werb Z, Fitzgerald ML, Chiu K, Corwin NM,
Esteves RA, Grobelny D, Galardy R, Damsky CH, Fisher SJ. 92-kD type IV
collagenase mediates invasion of human cytotrophoblasts.
J Cell Biol. 1991;113:437449.[Abstract/Free Full Text]
-
Rao JS, Steck PA, Tofilon P, Boyd D, Ali-Osman F,
Stetler-Stevenson WG, Liotta LA, Sawaya R. Role of
plasminogen activator and of 92-kDa type IV
collagenase in glioblastoma invasion using an in
vitro matrigel model. J Neurooncol. 1994;18:129138.[Medline]
[Order article via Infotrieve]
-
Watanabe H, Nakanishi I, Yamashita K, Hayakawa T, Okada
Y. Matrix metalloproteinase-9 (92 kDa gelatinase/type IV
collagenase) from U937 monoblastoid cells: correlation with
cellular invasion. J Cell Sci. 1993;104:991999.[Abstract]
-
Xia M, Leppert D, Hauser SL, Sreedharan SP, Nelson PJ,
Krensky AM, Goetzl EJ. Stimulus specificity of matrix metalloproteinase
dependence of human T cell migration through a model basement membrane.
J Immunol.. 1996;156:160167.[Abstract]
-
Murphy G, Crabbe T. Gelatinases A and B. Methods
Enzymol. 1995;248:470484.[Medline]
[Order article via Infotrieve]
-
Katsuda S, Okada Y, Imai K, Nakanishi I. Matrix
metalloproteinase-9 (92-kd gelatinase/type IV
collagenase equals gelatinase B) can degrade
arterial elastin. Am J Pathol. 1994;145:12081218.[Abstract]
-
Okada Y, Gonoji Y, Naka K, Tomita K, Nakanishi I, Iwata
K, Yamashita K, Hayakawa T. Matrix metalloproteinase 9 (92-kDa
gelatinase/type IV collagenase) from HT 1080 human
fibrosarcoma cells: purification and activation of the precursor and
enzymic properties. J Biol Chem. 1992;267:2171221719.[Abstract/Free Full Text]
-
Aimes RT, Quigley JP. Matrix metalloproteinase-2 is an
interstitial collagenase: inhibitor-free enzyme catalyzes the cleavage
of collagen fibrils and soluble native type I collagen generating the
specific 3/4- and 1/4-length fragments. J Biol Chem.. 1995;270:58725876.[Abstract/Free Full Text]
-
Sato H, Takino T, Okada Y, Cao J, Shinagawa A, Yamamoto
E, Seiki M. A matrix metalloproteinase expressed on the surface of
invasive tumour cells. Nature. 1994;370:6165.[Medline]
[Order article via Infotrieve]
-
Kinoshita T, Sato H, Takino T, Itoh M, Akizawa T, Seiki
M. Processing of a precursor of 72-kilodalton type IV
collagenase/gelatinase A by a recombinant membrane-type 1
matrix metalloproteinase. Cancer Res. 1996;56:25352538.[Abstract/Free Full Text]
-
Brooks BP, Stromblad S, Sanders LC, von Schalscha TL,
Stettler-Stevenson WG, Quigley JP, Cheresh DA. Localization of matrix
metalloproteinase MMP-2 to the surface of invasive cells by interaction
with integrin avb3.
Cell. 1996;85:683693.[Medline]
[Order article via Infotrieve]
-
Murphy G, Atkinson S, Ward R, Gavrilovic J, Reynolds
JJ. The role of plasminogen activators in the
regulation of connective tissue metalloproteinases. Ann N Y Acad
Sci. 1992;667:112.
-
Ogata Y, Enghild JJ, Nagase H. Matrix metalloproteinase
3 (stromelysin) activates the precursor for the human matrix
metalloproteinase 9. J Biol Chem. 1992;267:35813584.[Abstract/Free Full Text]
-
Fridman R, Toth M, Pena D, Mobashery S. Activation of
progelatinase B (MMP-9) by gelatinase A (MMP-2). Cancer Res. 1995;55:25482555. Abstract.[Abstract/Free Full Text]
-
Desrivières S, Lu H, Peyri N, Soria C, Legrand Y,
Ménashi S. Activation of the 92 kDa type IV
collagenase by tissue kallikrein. J Cell
Physiol. 1993;157:587593.[Medline]
[Order article via Infotrieve]
-
Jawien A, Bowen-Pope DF, Lindner V, Schwartz SM, Clowes
AW. Platelet-derived growth factor promotes smooth muscle migration
and intimal thickening in a rat model of balloon angioplasty.
J Clin Invest. 1992;89:507511.
-
George SJ, Williams A, Newby AC. An essential role for
platelet-derived growth factor in neointima formation
in human saphenous vein in vitro.
Atherosclerosis. 1996;120:227240.[Medline]
[Order article via Infotrieve]
-
Lindner V, Olson NE, Clowes AW, Reidy MA. Inhibition of
smooth muscle cell proliferation in injured rat arteries: interaction
of heparin with basic fibroblast growth factor. J Clin
Invest. 1992;90:20442049.
-
Villaschi S, Nicosia RF. Angiogenic role of
endogenous basic fibroblast growth factor released by rat
aorta after injury. Am J Pathol. 1993;143:181190.[Abstract]
-
Galis ZS, Muszynski M, Sukhova GK, Simon-Morrissey E,
Unemori EN, Lark MW, Amento E, Libby P. Cytokine-stimulated human
vascular smooth muscle cells synthesize a complement of enzymes
required for extracellular matrix digestion. Circ Res.. 1994;75:181189.[Abstract/Free Full Text]
-
Thie M, Harrach B, Shonherr E, Kresse H, Robenek H,
Rauterberg J. Responsiveness of aortic smooth muscle cells to soluble
growth mediators is influenced by cell-matrix contact.
Arterioscler Thromb.. 1993;13:9941004.[Abstract/Free Full Text]
-
Cahill PA, Hassid A. Differential
antimitogenic effectiveness of atrial
natriuretic peptides in primary versus subcultured rat
aortic smooth muscle cells: relationship to expression of ANF-C
receptors. J Cell Physiol. 1993;154:2838.[Medline]
[Order article via Infotrieve]
-
Bilato C, Pauly RR, Melillo G, Monticone R,
Gorelick-Feldman D, Gluzband YA, Sollott SJ, Ziman B, Lakatta EG, Crow
MT. Intracellular signaling pathways required for rat vascular smooth
muscle cell migration: interactions between basic fibroblast growth
factor and platelet-derived growth factor. J Clin
Invest. 1995;96:19051915.
-
Fabunmi RP, Baker AH, Murray EJ, Booth RFG, Newby AC.
Divergent regulation by growth factors and cytokines of 95 kDa
and 72 kDa gelatinases and tissue inhibitors of
metalloproteinases-1, -2 and -3 in rabbit aortic smooth muscle cells.
Biochem J. 1996;315:335342.
-
Seifert RA, Hart CE, Phillips PE, Forstrom JW, Ross R,
Murray MJ, Bowen-Pope DF. Two different subunits associate to create
isoform-specific platelet-derived growth factor receptors.
J Biol Chem. 1989;264:87718778.[Abstract/Free Full Text]
-
More RS, Rutty G, Underwood MJ, Brack MJ, Gershlick AH.
Assessment of myointimal cellular kinetics in a model of angioplasty by
means of proliferating cell nuclear antigen expression. Am
Heart J. 1994;128:681686.[Medline]
[Order article via Infotrieve]
-
Lindner V, Giachelli CM, Schwartz SM, Reidy MA. A
subpopulation of smooth muscle cells in injured rat arteries expresses
platelet-derived growth factor-B chain mRNA. Circ Res. 1995;76:951957.[Abstract/Free Full Text]
-
Uchida K, Sasahara M, Morigami N, Hazama F, Kinoshita
M. Expression of platelet-derived growth factor B-chain in
neointimal smooth muscle cells of balloon injured rabbit
femoral arteries. Atherosclerosis. 1996;124:923.[Medline]
[Order article via Infotrieve]
-
Ueda M, Becker AE, Kasayuki N, Kojima A, Morita Y,
Tanaka S. In situ detection of platelet-derived growth
factor-A and -B chain mRNA in human coronary arteries after
percutaneous transluminal coronary angioplasty.
Am J Pathol. 1996;149:831843.[Abstract]
-
Majesky MW, Reidy MA, Bowen-Pope DF, Hart CE, Wilcox
JN, Schwartz SM. PDGF ligand and receptor gene expression during repair
of arterial injury. J Cell Biol. 1990;111:21492158.[Abstract/Free Full Text]
-
Miano JM, Vlasic N, Tota RR, Stemerman MB. Smooth
muscle cell immediate-early gene and growth factor activation follows
vascular injury: a putative in vivo mechanism for autocrine growth.
Arterioscler Thromb. 1993;13:211219.[Abstract/Free Full Text]
-
Murry CE, Bartosek T, Giachelli CM, Alpers CE, Schwartz
SM. Platelet-derived growth factor-A mRNA expression in fetal,
normal adult, and atherosclerotic human aortas: analysis by
competitive polymerase chain reaction. Circulation. 1996;93:10951106.[Abstract/Free Full Text]
-
Crowley ST, Ray CJ, Nawaz DF, Majack RA, Horwitz LD.
Multiple growth factors are released from mechanically injured vascular
smooth muscle cells. Am J Physiol. 1995;269:H1641H1647.[Abstract/Free Full Text]
-
Raines EW, Dower SK, Ross R. Interleukin-1
mitogenic activity for fibroblasts and smooth muscle cells
is due to PDGF-AA. Science. 1989;243:393396.[Abstract/Free Full Text]
-
Battegay EJ, Raines EW, Seifert RA, Bowen-Pope DF, Ross
R. TGF-ß induces bimodal proliferation of connective tissue
cells via complex control of an autocrine PDGF loop. Cell. 1990;63:515524.[Medline]
[Order article via Infotrieve]
-
Calara F, Ameli S, Hultgardh-Nilsson A, Cercek B,
Kupfer J, Hedin U, Forrester J, Shah PK, Nilsson J. Autocrine induction
of DNA synthesis by mechanical injury of cultured smooth muscle cells:
potential role of FGF and PDGF. Arterioscler Thromb Vasc
Biol. 1996;16:187193.[Abstract/Free Full Text]
This article has been cited by other articles:

|
 |

|
 |
 
M. Ogawa, J.-i. Suzuki, K. Hishikari, K. Takayama, H. Tanaka, and M. Isobe
Clarithromycin Attenuates Acute and Chronic Rejection Via Matrix Metalloproteinase Suppression in Murine Cardiac Transplantation
J. Am. Coll. Cardiol.,
May 20, 2008;
51(20):
1977 - 1985.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. G. Dayer, B. Jenny, M.-O. Sauvain, G. Potter, P. Salmon, E. Zgraggen, M. Kanemitsu, E. Gascon, S. Sizonenko, D. Trono, et al.
Expression of FGF-2 in neural progenitor cells enhances their potential for cellular brain repair in the rodent cortex
Brain,
November 1, 2007;
130(11):
2962 - 2976.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Somers and M. Knaapen
The Histopathology of Varicose Vein Disease
Angiology,
October 1, 2006;
57(5):
546 - 555.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
G. M. Risinger Jr., T. S. Hunt, D. L. Updike, E. C. Bullen, and E. W. Howard
Matrix Metalloproteinase-2 Expression by Vascular Smooth Muscle Cells Is Mediated by Both Stimulatory and Inhibitory Signals in Response to Growth Factors
J. Biol. Chem.,
September 8, 2006;
281(36):
25915 - 25925.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. K. Sen, S. Khanna, and S. Roy
Perceived hyperoxia: Oxygen-induced remodeling of the reoxygenated heart
Cardiovasc Res,
July 15, 2006;
71(2):
280 - 288.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Kodali, M. Hajjou, A. B. Berman, M. B. Bansal, S. Zhang, J. J. Pan, and A. D. Schecter
Chemokines induce matrix metalloproteinase-2 through activation of epidermal growth factor receptor in arterial smooth muscle cells
Cardiovasc Res,
February 15, 2006;
69(3):
706 - 715.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Filippov, G. C. Koenig, T.-H. Chun, K. B. Hotary, I. Ota, T. H. Bugge, J. D. Roberts, W. P. Fay, H. Birkedal-Hansen, K. Holmbeck, et al.
MT1-matrix metalloproteinase directs arterial wall invasion and neointima formation by vascular smooth muscle cells
J. Exp. Med.,
September 6, 2005;
202(5):
663 - 671.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Rodriguez-Pla, J. A. Bosch-Gil, J. Rossello-Urgell, P. Huguet-Redecilla, J. H. Stone, and M. Vilardell-Tarres
Metalloproteinase-2 and -9 in Giant Cell Arteritis: Involvement in Vascular Remodeling
Circulation,
July 12, 2005;
112(2):
264 - 269.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. S. Garanich, M. Pahakis, and J. M. Tarbell
Shear stress inhibits smooth muscle cell migration via nitric oxide-mediated downregulation of matrix metalloproteinase-2 activity
Am J Physiol Heart Circ Physiol,
May 1, 2005;
288(5):
H2244 - H2252.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Levitzki
PDGF receptor kinase inhibitors for the treatment of restenosis
Cardiovasc Res,
February 15, 2005;
65(3):
581 - 586.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Tazaki, K. Minoguchi, T. Yokoe, K. T. R. Samson, H. Minoguchi, A. Tanaka, Y. Watanabe, and M. Adachi
Increased Levels and Activity of Matrix Metalloproteinase-9 in Obstructive Sleep Apnea Syndrome
Am. J. Respir. Crit. Care Med.,
December 15, 2004;
170(12):
1354 - 1359.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Zahradka, G. Harding, B. Litchie, S. Thomas, J. P. Werner, D. P. Wilson, and N. Yurkova
Activation of MMP-2 in response to vascular injury is mediated by phosphatidylinositol 3-kinase-dependent expression of MT1-MMP
Am J Physiol Heart Circ Physiol,
December 1, 2004;
287(6):
H2861 - H2870.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. S. Yao, Y. Chen, W. Zhai, K. Xu, W. L. Young, and G.-Y. Yang
Minocycline Exerts Multiple Inhibitory Effects on Vascular Endothelial Growth Factor-Induced Smooth Muscle Cell Migration: The Role of ERK1/2, PI3K, and Matrix Metalloproteinases
Circ. Res.,
August 20, 2004;
95(4):
364 - 371.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Shofuda, K.-i. Shofuda, N. Ferri, R. D. Kenagy, E. W. Raines, and A. W. Clowes
Cleavage of Focal Adhesion Kinase in Vascular Smooth Muscle Cells Overexpressing Membrane-Type Matrix Metalloproteinases
Arterioscler. Thromb. Vasc. Biol.,
May 1, 2004;
24(5):
839 - 844.
[Abstract]
[Full Text]
|
 |
|

|
 |

|
 |
 
X. W. Cheng, M. Kuzuya, T. Sasaki, K. Arakawa, S. Kanda, D. Sumi, T. Koike, K. Maeda, N. Tamaya-Mori, G.-P. Shi, et al.
Increased Expression of Elastolytic Cysteine Proteases, Cathepsins S and K, in the Neointima of Balloon-Injured Rat Carotid Arteries
Am. J. Pathol.,
January 1, 2004;
164(1):
243 - 251.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. S. Buetow, K. A. Tappan, J. R. Crosby, R. A. Seifert, and D. F. Bowen-Pope
Chimera Analysis Supports a Predominant Role of PDGFR{beta} in Promoting Smooth-Muscle Cell Chemotaxis after Arterial Injury
Am. J. Pathol.,
September 1, 2003;
163(3):
979 - 984.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Q. Liu, C. Tieche, D. Tang, and P. Alkema
Pattern formation of vascular smooth muscle cells subject to nonuniform fluid shear stress: role of PDGF-{beta} receptor and Src
Am J Physiol Heart Circ Physiol,
August 7, 2003;
285(3):
H1081 - H1090.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Z. S. Galis, C. Johnson, D. Godin, R. Magid, J. M. Shipley, R. M. Senior, and E. Ivan
Targeted Disruption of the Matrix Metalloproteinase-9 Gene Impairs Smooth Muscle Cell Migration and Geometrical Arterial Remodeling
Circ. Res.,
November 1, 2002;
91(9):
852 - 859.
[Abstract]
[Full Text]
[PDF]
|
 |
|