© 1996 American Heart Association, Inc.
Articles |
Regulation of Vascular Smooth Muscle Cell Migration and Proliferation In Vitro and in Injured Rat Arteries by a Synthetic Matrix Metalloproteinase Inhibitor
From the Department of Surgery, University of Washington, Seattle.
Correspondence to Alexander W. Clowes, MD, Department of Surgery, RF-25, University of Washington, Seattle, WA 98195.
 |
Abstract |
|---|
 Top Abstract IntroductionMethods Results Discussion References |
|---|
Abstract Smooth muscle cell (SMC) migration and proliferation and extracellular matrix remodeling are essential aspects of the arterial response to injury, vessel development, and atherogenesis. Matrix metalloproteinase (MMP) expression is associated with SMC proliferation and migration after arterial injury. To assess the role of MMPs in SMC proliferation and migration and intimal thickening, we measured the effect of the synthetic MMP inhibitor BB94 (Batimastat) on DNA synthesis and migration of SMCs in vitro as well as the formation of a neointima after balloon injury to the rat carotid artery. BB94 dose-dependently inhibited SMC migration induced by platelet-derived growth factor (PDGF)–BB through a filter coated with a thick basement membrane matrix (Matrigel) layer but did not show any inhibitory effect on SMC migration through a lightly coated filter. At concentrations up to 1 µmol/L, BB94 did not alter DNA synthesis induced by PDGF-AA or PDGF-BB. Treatment with 30 mg BB94·kg-1·d-1 IP for 7 or 14 days after balloon injury to the rat carotid artery decreased the total number of intimal SMC nuclei and suppressed intimal thickening. SMC proliferation (5-bromo-2'-deoxyuridine labeling) was decreased in the media at 2 days, whereas it was increased in the intima at 7 but not 14 days. These results suggest that BB94 inhibits intimal thickening after arterial injury by decreasing SMC migration and proliferation and support the conclusion that MMPs play a significant role in regulating intimal thickening in injured arteries.
Key Words: metalloproteinases • smooth muscle cells • rats • arterial injury • migration
|
Introduction |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
SMC proliferation and migration and ECM remodeling are important for intimal hyperplasia after arterial injury1 2 3 and vascular grafting4 5 and in atherosclerosis.6 These events are regulated by various cytokines and growth factors secreted by platelets and vascular cells6 and might depend on matrix degradation by enzymes such as MMPs, plasminogen activators, and plasminogen. This hypothesis is based on observations in other physiological settings requiring tissue growth (tumor metastasis, wound healing, and organ remodeling).7 8 9 10 11 MMPs expressed in human atherosclerotic lesions include interstitial collagenase (MMP-1), 72-kD type IV collagenase (MMP-2), stromelysin (MMP-3), and 92-kD type IV collagenase (MMP-9).12 13 14 We reported15 16 that the expression and activation of 72-kD type IV collagenase and 92-kD type IV collagenase by SMCs are associated with increased SMC proliferation and migration after arterial injury. SMC expression of tissue-type plasminogen activator is associated with migration and that of urokinase-type plasminogen activator with mitogenesis in the balloon-injured rat carotid artery.17 Plasminogen increases SMC migration from baboon arterial explants in a urokinase-type and tissue-type plasminogen activator–dependent manner.18 19 This is of particular interest because plasminogen, when converted to plasmin by plasminogen activators, degrades a broad range of matrix molecules and can activate interstitial collagenase, stromelysin, and 92-kD type IV collagenase.20 21 These reports suggest that MMPs and other proteases may play a role in vascular remodeling.
To test the hypothesis that MMPs are required for SMC proliferation and migration, we determined whether a synthetic metalloproteinase inhibitor, BB94, inhibits these processes in vitro and in vivo.
|
Methods |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Reagents
A synthetic MMP inhibitor, BB94 (Batimastat) {[4-(N-hydroxyamino)-2R-isobutyl-3S-(thienyl-thiomethyl)-succinyl]-L-phenylalanine-N-methylamide, MW 478}, was provided by British Biotechnology Limited. BB94 contains a peptide backbone that binds to the MMP and a hydroxamic acid group that binds to the catalytically active zinc atom. The concentrations of BB94 producing 50% inhibition against the MMPs are interstitial collagenase, 5 nmol/L; 72-kD type IV collagenase, 4 nmol/L; stromelysin, 20 nmol/L; and 92-kD type IV collagenase, 1 to 10 nmol/L.22 The activity of 72-kD and 92-kD type IV collagenases in gelatin zymograms of rat SMC–conditioned medium was inhibited by 1 to 10 nmol/L BB94 (unpublished data). Recombinant human PDGF-BB was kindly supplied by Dr Charles Hart (Zymogenetics, Inc); it was produced in a yeast expression system as described previously23 and purified to >95% homogeneity. 3H-Thymidine was purchased from Amersham.
Cell Culture
Rat aortic medial SMCs grown in Dulbecco's
modified Eagle's
medium (DMEM) supplemented with 10% fetal bovine serum, 200 µg
streptomycin/mL, and 200 U penicillin/mL (GIBCO Laboratories) were
isolated by the explant method. Cells were used between passages 3 and
15. In immunohistochemical preparations, SMCs stained positive for
smooth muscle 
-actin (mouse anti-human smooth muscle
-actin, Boehringer Mannheim Corp).
SMC DNA Synthesis
Confluent SMCs were trypsinized, suspended
in DMEM plus 10%
fetal bovine serum with streptomycin and penicillin, and seeded at
2.5x104 cells per well into 24-well plates (Corning Co).
After 6 hours, the cells were washed with PBS, and the medium was
changed to DMEM containing insulin (10 µg/mL), transferrin (5
µg/mL), and ovalbumin (1 mg/mL) to allow the cells to
become quiescent. After 2 days, PDGF-BB at 10 ng/mL was added directly
to the serum-free medium, and the cells were incubated an
additional 20 hours at 37°C. 3H-Thymidine (1 µCi/well)
was then added for an additional 6 hours. Incorporation of
3H-thymidine into the trichloroacetic
acid–precipitable fraction was determined as previously
described.24 BB94 was solubilized in ethanol at a
concentration of 10 mmol/L. BB94 was added to the cells at final
concentrations between 1 nmol/L and 1 µmol/L 1 hour before the
addition of PDGF-BB.
SMC Migration Assay
Migration of SMCs was assayed with
polycarbonate filters
(Nucleopore Corp) having 5.0-µm pores in 48-well chemotaxis chambers
(Neuro Probe Inc).25 The filters were coated in one of two
ways. Either 2.7 µg/well of Matrigel (Collaborative Research), a
basement membrane preparation, was dried at room temperature and
reconstituted with distilled water before the assay,26 or
filters were incubated in 100 µg/mL of Vitrogen (mainly type I
collagen; Celtrix Pharmaceuticals, Inc) overnight at room temperature
and dried. Cultured SMCs were trypsinized and suspended at a
concentration of 5.0x105 cells/mL in serum-free DMEM
with streptomycin and penicillin. A volume of 50 µL of SMC suspension
was placed in the upper chamber, and 25 µL of DMEM containing 10
ng/mL of PDGF-BB was placed in the lower chamber. In some experiments,
the SMC suspension was mixed with increasing concentrations of BB94
before it was placed in the upper chamber. The chamber was incubated at
37°C for 24 hours. For the migration experiments with filters coated
with a thin layer of Vitrogen, the chamber was incubated for 4 hours.
After incubation, the filters were removed and the SMCs on the upper
side of the filter were scraped off. The SMCs that had migrated to the
lower side of the filter were fixed in methanol, stained with
Diff-Quick staining solution (Baxter), and counted under a microscope
(x100) for quantification of SMC migration. Migration activity was
expressed as the mean number of cells that had migrated per x100
field.
Animal Model
Three-month-old male Sprague-Dawley rats (370
to 400 g) were obtained from Bantin & Kingman, Inc. Rats were
anesthetized with 1.0 mL/kg IM of a solution containing
acepromazine 1 mg/mL (Fermenta Animal Health Corp), ketamine 50
mg/mL (Aveco, Inc), and xylazine 5 mg/mL (Mobay Corp) in saline and
were cared for according to the `Principles of Laboratory Animal
Care' (formulated by the National Society for Medical Research) and
the Guide for the Care and Use of Laboratory Animals (NIH
publication 86-23, revised 1985). Endothelial
denudation was performed in the left common carotid artery by the
passage of a 2F balloon embolectomy catheter (V. Mueller) as described
previously.1 A 2.5-mg/mL suspension of BB94 was made by
sonication in PBS, pH 7.2, with Tween-80 (0.01%).22 Rats
received a daily injection of the BB94 suspension at 1 to 30
mg·kg-1·d-1 IP from 2 to 14
days.
Control animals were given vehicle alone.
Morphometry
Animals were killed with an overdose of
pentobarbital, and the
carotid arteries were fixed by perfusion with 10% formalin or 4%
paraformaldehyde in PBS, pH 7.4, at 100 mm Hg. The
arteries were embedded in paraffin (two segments per animal),
cross-sectioned, and stained with hematoxylin-eosin. Intimal
and medial cross-sectional areas were measured as described
previously,27 and the total number of nuclei in each cross
section was also counted.
Measurement of SMC Proliferation in Tissues
The thymidine
analogue BrdU (Boehringer Mannheim Corp)
was injected (30 mg/kg IP) at 1, 9, and 17 hours before death. In some
experiments, a tablet containing 50 mg of BrdU was placed
subcutaneously 20 hours before death. The BrdU labeling index (the
fraction of labeled nuclei times 100) was determined as described
previously28 by use of a monoclonal antibody against BrdU
(Boehringer Mannheim Corp) on histological
cross sections.
Statistical Analysis
In vitro experiments were analyzed by
one-tailed
t tests. In vivo experiments were analyzed by the
Mann-Whitney U test for comparisons of two groups or, for
comparing multiple groups, the Kruskal-Wallis test (an extension of the
Mann-Whitney test) with Dunn's correction for multiple comparisons. To
determine whether BB94 increased the 7-day intimal BrdU labeling index,
post hoc analysis was performed with a two-tailed
t test. This analysis was confirmed
(P<.04, BB94 versus control) by permutation
analysis,29 with the test statistic being the
difference between the means.
|
Results |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
Effects of BB94 on Migration and Proliferation of Cultured SMCs
SMC migration through Matrigel was stimulated by PDGF-BB at the maximally effective dose of 10 ng/mL.30 BB94 dose-dependently suppressed the migration through a thick layer of Matrigel (Fig 1
). In contrast, BB94 at concentrations up
to 100 nmol/L did not suppress SMC migration through filters lightly
coated with Vitrogen. In either type of coating, BB94 did not alter
cell attachment to the upper side of the membrane (unpublished
data).
|
Proliferation (3H-thymidine incorporation) was
stimulated
by 10 ng/mL of either PDGF-AA or PDGF-BB. PDGF-AA increased
3H-thymidine incorporation by 2.1-fold over control, and
PDGF-BB increased it by 8.2-fold. BB94 at concentrations from 1 nmol/L
to 1 µmol/L had no effect on 3H-thymidine incorporation
in either unstimulated SMCs or SMCs stimulated by PDGF-AA or PDGF-BB
(Fig 2).
|
Suppression of Intimal Thickening in Balloon-Injured Rat Carotid
Artery by BB94
Seven days after balloon injury to the left carotid
artery,
intimal area was increased to 0.037±0.013 mm2. Uninjured
controls did not exhibit intimal thickening.1
Intraperitoneal administration of BB94 at 30
mg·kg-1·d-1 decreased intimal
area by
50% (Fig 3A versus 3B; Fig 4A). BB94
also decreased the total number of SMC nuclei in the intimal layer by
40% at 7 days (Fig 4B). Medial area was not changed
(0.135±0.009 and
0.124±0.013 mm2 for control and BB94, respectively;
n=10).
At 14 days, the effect of BB94 on intimal area was less, with a
decrease of only 26% (Figs 3C, 3D, and
5A), whereas the
total number of intimal SMC nuclei was decreased by 30% (Fig
5B).
Medial area was not altered by treatment with BB94 (0.145±0.057 and
0.126±0.019 mm2 for control and BB94, respectively;
n=10).
|
|
|
To determine whether BB94 inhibited SMC proliferation, we
measured the
fraction of cells labeled with BrdU at 2, 7, and 14 days after carotid
artery injury. BB94 decreased the BrdU labeling index in the media at 2
days after injury (Fig 6) but not at 7 or 14 days. The
intimal BrdU-labeling index was increased by BB94 at 7 days but not
altered at 14 days (Fig 6).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
In this study, we demonstrate that the potent MMP inhibitor BB94 suppresses intimal thickening after arterial injury. BB94 also inhibited the initial wave of proliferation in the media from day 1 to day 2 after injury, although it had no significant effect on medial proliferation at later times. The synthetic MMP inhibitors Ro31-4724 and Ro31-7467 were reported to decrease entry into the S phase by SMCs in rabbit aortic explants.31 In contrast, previous results using different MMP inhibitors showed no effect on medial SMC proliferation in vivo after labeling between days 3 and 4.16 BB94 had no effect on SMC proliferation in vitro but inhibited SMC migration through Matrigel. Whether the lack of an effect of BB94 on proliferation is the result of phenotypic changes in SMCs caused by culture in vitro is not known, but this result confirms previous observations on other cell lines, such as Chinese hamster ovary cells, human foreskin fibroblasts, and various cancer cells.22 We have also observed that BB94 inhibits the migration of SMCs from baboon arterial explants in vitro.32 Together, these observations suggest that MMP inhibitors may inhibit migration and only the first wave of SMC proliferation in vivo. The maintenance of inhibitory levels of BB94 for as long as 6 months of treatment in rats (Alan Galloway, PhD, British Biotech, Ltd, personal communication, 1995) indicates that the lack of an effect of BB94 on medial proliferation after 2 days does not result from increasing metabolism of BB94.
In contrast to the effect of BB94 on medial SMC proliferation,
proliferation in the intima was increased by BB94 at 7 days but not 14
days. The reason for this difference is not clear but may be the result
of differences in the cells or the matrix surrounding the cells or may
be a compensatory response to hemodynamic forces that
results from the reduced migration of SMCs into the intima. Regarding
the former possibility, intimal and medial SMCs demonstrate many
differences. For example, intimal SMCs express less
1-integrin33 and can produce more
PDGF34 and migrate faster35 in culture than
medial SMCs. Concerning the matrix, it is clear that matrix components
can signal cells (for example, via integrins) and influence SMC
differentiation and growth.36 BB94 might alter turnover of
matrix binding sites. BB94 can inhibit the turnover of proteoglycans in
cartilage,37 and if this is true for SMCs, the balance of
growth-inhibitory and -stimulatory factors in the
matrix (eg, heparan sulfate proteoglycans and fibroblast growth factor)
may be altered to favor proliferation in the intima and inhibition in
the media. Finally, vascular growth is regulated by
hemodynamic forces such as flow and shear
stress38 39 40 that may determine final
intimal size. These
factors may cause increased proliferation in the intima as a
compensatory response to decreased SMC migration from the media.
BB94 had less effect on intimal area and SMC number at 14 days than 7 days. In a preliminary report, Prescott and colleagues41 found that an MMP inhibitor also significantly decreased intimal thickening in the injured rat carotid artery after 7 days but had no effect at 21 days. One explanation for this is the increased intimal proliferation at 7 days after treatment with BB94. Another possibility is that BB94 increased ECM by decreasing matrix degradation. However, BB94 did not alter the number of nuclei per square millimeter in the intima at 14 days (ie, cell density) and by inference did not affect the amount of matrix per square millimeter. So even though BB94 decreased the absolute number of cells in the intima, there was a proportional decrease in matrix. In addition, there was no effect of treatment with BB94 on histochemical staining for collagen, elastin, and proteoglycans (unpublished data, 1995). These results indicate to us that BB94 did not increase the accumulation of matrix.
These effects of BB94 are probably mediated through the inhibition of MMP activity. BB94 inhibited SMC migration in vitro when a thick layer of Matrigel was present on the filter but failed to do so when the membranes were lightly coated. A matrix-dependent inhibitory effect on SMC migration in vitro was also demonstrated for antibodies to 72-kD type IV collagenase and peptides of the amino terminus of pro–72-kD type IV collagenase.42 Wang and colleagues43 reported that the blood levels of BB94 administered at 30 mg·kg-1·d-1 IP in mice were 10-fold higher than the IC50 for various MMPs; rats given 25 mg·kg-1·d-1 BB94 also attain levels >50 nmol/L in whole blood (Alan Galloway, PhD, British Biotech, Ltd, personal communication, 1995), well in excess of the IC50s of 72- and 92-kD type IV collagenase, interstitial collagenase, and stromelysin.22
It is not clear which MMPs play a role in the formation of the neointima. However, we recently showed that activation of 72-kD type IV collagenase is associated with SMC migration into the intima 4 to 5 days after arterial injury.15 16 This finding is consistent with the report of Pauly and coworkers,42 who found that antibodies to 72-kD type IV collagenase inhibit rat SMC migration through Matrigel in vitro. In addition, the expression of 92-kD type IV collagenase is increased within 24 hours after arterial injury as SMCs are entering the S phase. The activity of 92-kD type IV collagenase decreases thereafter.15 16 Our present results showing inhibition of medial SMC mitogenesis at 2 days suggest that 92-kD type IV collagenase may be involved in entry into the cell cycle by medial SMCs. Although these data do not rule out a role for other MMPs in SMC proliferation and migration, we have been unable to detect interstitial collagenase (MMP-1), stromelysin (MMP-3), or matrilysin (MMP-7) in the injured rat carotid artery.15
Inhibition of MMP activity by BB94 may alter cell function in more dynamic ways than just blocking the degradation of a simple physical barrier to migration. It is possible that some ECM proteins provide inhibitory signals to migration. Elastin peptides and fibronectin decrease SMC migration.44 In addition, we recently reported that heparan sulfate proteoglycans potentiate a migration-inhibitory signal induced by PDGF-AA in cultured SMCs.45 Matrix factors like fibronectin, elastin, and proteoglycans are substrates for MMPs and would be protected by treatment with BB94. A second way BB94 might act could be by changing the matrix that SMCs interact with, which in turn might alter the ability of SMCs to produce MMPs.46 Attachment of human alveolar macrophages to collagen types I and III but not type IV, laminin, fibronectin, or elastin augments the production of interstitial collagenase.47 Similar results have been reported for keratinocytes.48 The interactive effects of matrix proteins are illustrated by the observation that expression of several MMPs is increased in human synovial fibroblasts when cells are plated on a mixture of fibronectin and tenascin but not on fibronectin alone.49 These effects of the ECM on MMP expression are mediated in part by integrins.46 50 51 52
The effects of MMPs and other proteinases on cell migration, tissue development, and tissue remodeling depend on the balance of these proteinases with their endogenous inhibitors, such as TIMP-1 and -2 and PAI-1.53 54 55 56 For example, increased activity of interstitial collagenase, 72-kD and 92-kD type IV collagenases, and stromelysin is associated with accelerated tumor metastasis as well as angiogenesis.53 54 57 58 59 60 Members of the TIMP family of proteinase inhibitors and synthetic metalloproteinase inhibitors block tumor invasion and metastasis in vitro and in vivo,22 43 61 62 angiogenesis,63 64 65 collagen degradation by endothelial cells,66 and mammary gland involution.11 SMCs that overexpress TIMP-1 have reduced capacity to migrate through ECM (unpublished data, 1995). TIMP-1, TIMP-2, PAI-1, plasminogen activators, and several MMPs are expressed in human atherosclerotic plaques12 13 14 67 68 ; TIMP-2, PAI-1, plasminogen activators, and several MMPs are increased with different kinetics after injury in rat carotid arteries.15 17 69 These observations suggest that there is a complex interplay among proteinases and their inhibitors in the vascular wall.
In conclusion, the synthetic MMP inhibitor BB94 inhibits SMC migration through ECM but has no effect on DNA synthesis in vitro. BB94 also suppresses intimal thickening after injury in rat arteries and has complex effects on SMC proliferation. Thus, MMPs may play an important role in SMC migration and proliferation during the arterial response to injury.
|
Selected Abbreviations and Acronyms |
|---|
|
|
Acknowledgments |
|---|
This study was supported by grant HL-18645 from the National Institutes of Health. We thank Reza Forough and David Hassenstab for valuable discussions and Monika M. Clowes for technical advice regarding animal experiments. We also thank Paul Sampson, Chris Volinsky, and Juanjuan Fan, Department of Statistics, University of Washington, for performing the permutation analysis.
Received June 23, 1995; accepted October 20, 1995.
|
References |
|---|
|
TopAbstractIntroductionMethods Results Discussion References |
|---|
1. Clowes AW, Reidy MA, Clowes MM. Kinetics of cellular proliferation after arterial injury, I: smooth muscle growth in the absence of endothelium. Lab Invest. 1983;49:327-333. [Medline] [Order article via Infotrieve]
2.
Clowes AW, Schwartz SM. Significance of
quiescent smooth muscle migration in the injured rat carotid
artery. Circ Res. 1985;56:139-145.
3. Clowes AW, Clowes MM, Reidy MA. Kinetics of cellular proliferation after arterial injury, III: endothelial and smooth muscle growth in chronically denuded vessels. Lab Invest. 1986;54:295-303. [Medline] [Order article via Infotrieve]
4. Clowes AW, Gown AM, Hanson SR, Reidy MA. Mechanisms of arterial graft failure, I: role of cellular proliferation in early healing of PTFE prostheses. Am J Pathol. 1985;118:43-54. [Abstract]
5. Clowes AW, Kirkman TR, Clowes MM. Mechanisms of arterial graft failure, II: chronic endothelial and smooth muscle cell proliferation in healing polytetrafluoroethylene prostheses. J Vasc Surg. 1986;3:877-884. [Medline] [Order article via Infotrieve]
6. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993;362:801-809. [Medline] [Order article via Infotrieve]
7.
Ossowski L. Invasion of connective tissue by
human carcinoma cell lines: requirement for urokinase, urokinase
receptor, and interstitial collagenase.
Cancer Res. 1992;52:6754-6760.
8. Stetler-Stevenson WG, Liotta LA, Kleiner DE Jr. Extracellular matrix 6: role of matrix metalloproteinases in tumor invasion and metastasis. FASEB J. 1993;7:1434-1441. [Abstract]
9. Kirchheimer JC, Remold HG. Endogenous receptor-bound urokinase mediates tissue invasion of human monocytes. J Immunol. 1989;143:2634-2639. [Abstract]
10. Matrisian LM, Gaire M, Rodgers WH, Osteen KG. Metalloproteinase expression and hormonal regulation during tissue remodeling in the cycling human endometrium. Contrib Nephrol. 1994;107:94-100. [Medline] [Order article via Infotrieve]
11.
Talhouk RS, Bissell MJ, Werb Z. Coordinated
expression of extracellular matrix-degrading proteinases and their
inhibitors regulates mammary epithelial function during
involution. J Cell Biol. 1992;118:1271-1282.
12. Galis ZS, Sukhova GK, Lark MW, Libby P. Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest. 1994;94:2493-2503.
13.
Henney AM, Wakeley PR, Davies MJ, Foster K, Hembry R,
Murphy G, Humphries S. Localization of stromelysin gene
expression in atherosclerotic plaques by in situ hybridization.
Proc Natl Acad Sci U S A. 1991;88:8154-8158.
14.
Brown DL, Hibbs MS, Kearney M, Loushin C, Isner
JM. Identification of 92-kD gelatinase in human coronary
atherosclerotic lesions: association of active enzyme synthesis with
unstable angina. Circulation. 1995;91:2125-2131.
15. 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;20:209-217. [Medline] [Order article via Infotrieve]
16.
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;75:539-545.
17.
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;67:61-67.
18. Kenagy RD, Hart C, Clowes AW. Role for growth factors and proteinases in the migration of smooth muscle cells through native extracellular matrix in vitro. FASEB J. 1993;7:A637.
19. Kenagy RD, Clowes AW. Primate smooth muscle cell migration from arterial explants depends on tissue plasminogen activator and urokinase activity. Circulation. 1995;92(suppl I):I-559. Abstract.
20. Nagase H, Enghild JJ, Suzuki K, Salveson G. Stepwise activation mechanisms of the precursor of matrix metalloproteinase 3 (stromelysin) by proteinases and (4-aminophenyl)mercuric acetate. Biochemistry. 1990;29:5783-5789. [Medline] [Order article via Infotrieve]
21. 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;667:1-12.
22.
Davies B, Brown PD, East N, Crimmin MJ, Balkwill
FR. A synthetic matrix metalloproteinase inhibitor
decreases tumor burden and prolongs survival of mice bearing human
ovarian carcinoma xenografts. Cancer Res. 1993;53:2087-2091.
23.
Kelly JD, Haldeman BA, Grant FJ, Murray MJ, Seifert RA,
Bowen-Pope DF, Cooper JA, Kazlauskas A. Platelet-derived
growth factor (PDGF) stimulates PDGF receptor subunit dimerization and
intersubunit trans-phosphorylation.
J Biol Chem. 1991;266:8987-8992.
24.
Raines EW, Ross R. Platelet-derived
growth factor. High yield purification and evidence for multiple
forms. J Biol Chem. 1982;257:5154-5160.
25.
Koyama N, Harada K, Yamamoto A, Morisaki N, Saito Y,
Yoshida S. Purification and characterization of an autocrine
migration factor for vascular smooth muscle cells (SMC): SMC-derived
migration factor. J Biol Chem. 1993;268:13301-13308.
26.
Albini A, Iwamoto Y, Kleinman HK, Martin GR,
Aaronson SA, Kozlowski JM, McEwan RN. A rapid in vitro assay for
quantitating the invasive potential of tumor cells.
Cancer Res. 1987;47:3239-3245.
27. Clowes AW, Reidy MA, Clowes MM. Mechanisms of stenosis after arterial injury. Lab Invest. 1983;49:208-215. [Medline] [Order article via Infotrieve]
28. Hardonk MJ, Harms G. The use of 5'-bromodeoxyuridine in the study of cell proliferation. Acta Histochem Suppl. 1990;XXXIX:99-108.
29. Good PI. Permutation Tests: A Practical Guide to Resampling Methods for Testing Hypotheses. New York, NY: Springer-Verlag; 1994:1.
30.
Koyama N, Morisaki N, Saito Y, Yoshida S.
Regulatory effects of platelet-derived growth factor-AA
homodimer on migration of vascular smooth muscle cells.
J Biol Chem. 1992;267:22806-22812.
31. Southgate KM, Davies M, Booth RFG, Newby AC. Involvement of extracellular-matrix-degrading metalloproteinases in rabbit aortic smooth-muscle cell proliferation. Biochem J. 1992;288:93-99.
32. Kenagy RD, Clowes AW. A possible role for MMP-2 and MMP-9 in the migration of primate arterial smooth muscle cells through native matrix. Ann N Y Acad Sci. 1994;732:462-465. [Medline] [Order article via Infotrieve]
33.
Belkin VM, Belkin AM, Koteliansky VE. Human
smooth muscle VLA-1 integrin: purification, substrate specificity,
localization in aorta, and expression during development.
J Cell Biol. 1990;111:2159-2170.
34.
Walker LN, Bowen-Pope DF, Reidy MA.
Production of platelet-derived growth factor-like
molecules by cultured arterial smooth muscle cells
accompanies proliferation after arterial injury.
Proc Natl Acad Sci U S A. 1986;83:7311-7315.
35.
Grunwald J, Haudenschild CC. Intimal injury in
vivo activates vascular smooth muscle cell migration and
explant outgrowth in vitro.
Arteriosclerosis. 1984;4:183-188.
36. Carey DJ. Control of growth and differentiation of vascular cells by extracellular matrix proteins. Annu Rev Physiol. 1991;53:161-177. [Medline] [Order article via Infotrieve]
37. Buttle DJ, Handley CJ, Ilic MZ, Saklatvala J, Murata M, Barratt AJ. Inhibition of cartilage proteoglycan release by a specific inactivator of cathepsin B and an inhibitor of matrix metalloproteinases: evidence for two converging pathways of chondrocyte-mediated proteoglycan degradation. Arthritis Rheum. 1993;12:1709-1717.
38.
Langille BL, O'Donnell F. Reductions in
arterial diameter produced by chronic decreases in blood
flow are endothelium-dependent.
Science. 1986;231:405-407.
39.
Kohler TR, Jawien A. Flow affects development of
intimal hyperplasia after arterial injury in rats.
Arterioscler Thromb. 1992;12:963-971.
40. Zwolak RM, Adams MC, Clowes AW. Kinetics of vein graft hyperplasia: association with tangential stress. J Vasc Surg. 1987;5:126-136. [Medline] [Order article via Infotrieve]
41. Prescott MF, Sawyer WK, Von Linden-Reed J. Matrix metalloproteinase inhibitor-induced reduction of smooth muscle cell migration does not inhibit late lesion formation following ballooning. FASEB J. 1995;9:A855.
42.
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;75:41-54.
43.
Wang X, Fu X, Brown PD, Crimmin MJ, Hoffman RM.
Matrix metalloproteinase inhibitor BB-94 (batimastat)
inhibits human colon tumor growth and spread in a patient-like
orthotopic model in nude mice. Cancer Res. 1994;54:4726-4728.
44.
Ohyama T, Fukuda K, Oda H, Nakamura H, Hikita Y.
Substratum-bound elastin peptide inhibits aortic smooth muscle cell
migration in vitro.
Arteriosclerosis. 1987;7:593-598.
45. Koyama N, Seki J, Harlan JM, Clowes AW. Extracellular matrix regulates smooth muscle cell migration and contributes to the migration-inhibitory mechanism of PDGF-AA. Circulation. 1994;90(suppl I):I-637. Abstract.
46. Werb Z, Tremble P, Damsky CH. Regulation of extracellular matrix degradation by cell-extracellular matrix interactions. Cell Differ Dev. 1990;32:299-306. [Medline] [Order article via Infotrieve]
47.
Shapiro SD, Kobayashi DK, Pentland AP, Welgus
HG. Induction of macrophage metalloproteinases by
extracellular matrix: evidence for enzyme- and substrate-specific
responses involving prostaglandin-dependent
mechanisms. J Biol Chem. 1993;268:8170-8175.
48. Saarialho-Kere UK, Kovacs SO, Pentland AP, Olerud JE, Welgus HG, Parks WC. Cell-matrix interactions modulate interstitial collagenase expression by human keratinocytes actively involved in wound healing. J Clin Invest. 1993;92:2858-2866.
49. Tremble P, Chiquet-Ehrismann R, Werb Z. The extracellular matrix ligands fibronectin and tenascin collaborate in regulating collagenase gene expression in fibroblasts. Mol Biol Cell. 1994;5:439-453. [Abstract]
50. Larjava H, Lyons JG, Salo T, Makela M, Koivisto L, Birkedal-Hansen H, Akiyama SK, Yamada KM, Heino J. Anti-integrin antibodies induce type IV collagenase expression in keratinocytes. J Cell Physiol. 1993;157:190-200. [Medline] [Order article via Infotrieve]
51.
Seftor REB, Seftor EA, Stetler-Stevenson WG, Hendrix
MJC. The 72 kDa type IV collagenase is modulated via
differential expression of vß3 and
5ß1 integrins during human melanoma cell
invasion. Cancer Res. 1993;53:3411-3415.
52.
Romanic AM, Madri JA. The induction of 72-kD
gelatinase in T cells upon adhesion to endothelial
cells is VCAM-1 dependent. J Cell Biol. 1994;125:1165-1178.
53. Matrisian LM. Metalloproteinases and their inhibitors in matrix remodeling. Trends Genet. 1990;6:121-125. [Medline] [Order article via Infotrieve]
54. Woessner JF Jr. Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J. 1991;5:2145-2154. [Abstract]
55. Rifkin DB, Tsuboi R, Mignatti P. The role of proteases in matrix breakdown during cellular invasion. Am Rev Respir Dis. 1989;140:1112-1113. [Medline] [Order article via Infotrieve]
56. Scully MF. Plasminogen activator-dependent pericellular proteolysis. Br J Haematol. 1991;79:537-543. [Medline] [Order article via Infotrieve]
57. Stetler-Stevenson WG. Type IV collagenases in tumor invasion and metastasis. Cancer Metastasis Rev. 1990;9:289-303. [Medline] [Order article via Infotrieve]
58. McDonnell S, Matrisian LM. Stromelysin in tumor progression and metastasis. Cancer Metastasis Rev. 1990;9:305-319. [Medline] [Order article via Infotrieve]
59.
Kalebic T, Garbisa S, Glaser B, Liotta LA.
Basement membrane collagen: degradation by migrating
endothelial cells. Science. 1983;221:281-283.
60.
Herron GS, Werb Z, Dwyer K, Banda MJ. Secretion
of metalloproteinases by stimulated capillary
endothelial cells. J Biol
Chem. 1986;261:2810-2813.
61.
Schultz RM, Silberman S, Persky B, Bajkowski AS,
Carmichael DF. Inhibition by human recombinant tissue
inhibitor of metalloproteinases of human amnion invasion
and lung colonization by murine B16-F10 melanoma cells.
Cancer Res. 1988;48:5539-5545.
62.
DeClerck YA, Yean T-D, Chan D, Shimada H, Langley
KE. Inhibition of tumor invasion of smooth muscle cell layers by
recombinant human metalloproteinase inhibitor.
Cancer Res. 1991;51:2151-2157.
63. Schnaper HW, Grant DS, Stetler-Stevenson WG, Fridman R, D'Orazi G, Murphy AN, Bird RE, Hoythya M, Fuerst TR, French DL, Quigley JP, Kleinman HK. Type IV collagenase(s) and TIMPs modulate endothelial cell morphogenesis in vitro. J Cell Physiol. 1993;156:235-246. [Medline] [Order article via Infotrieve]
64. Murphy AN, Unsworth EJ, Stetler-Stevenson WG. Tissue inhibitor of metalloproteinases-2 inhibits bFGF-induced human microvascular endothelial cell proliferation. J Cell Physiol. 1993;157:351-358. [Medline] [Order article via Infotrieve]
65. Moses MA, Langer R. A metalloproteinase inhibitor as an inhibitor of neovascularization. J Cell Biochem. 1991;47:230-235. [Medline] [Order article via Infotrieve]
66.
Gavrilovic J, Hembry RM, Reynolds JJ, Murphy G.
Tissue inhibitor of metalloproteinases (TIMP) regulates
extracellular type I collagen degradation by chondrocytes and
endothelial cells. J Cell
Sci. 1987;87:357-362.
67.
Schneiderman J, Sawdey MS, Keeton MR, Bordin GM,
Bernstein EF, Dilley RB, Loskutoff DJ. Increased type 1
plasminogen activator inhibitor
gene expression in atherosclerotic human arteries. Proc
Natl Acad Sci U S A. 1992;89:6998-7002.
68. Smokovitis A, Kokolis N, Alexaki-Tzivanidou E. Fatty streaks and fibrous plaques in human aorta show increased plasminogen activator activity. Haemostasis. 1988;18:146-153. [Medline] [Order article via Infotrieve]
69. Forough R, Hasenstab D, Zempo N, Langley K, DeClerck Y, Clowes AW. Induction of tissue inhibitor of metalloproteinase-2 in injured rat artery. Ann N Y Acad Sci. 1994;732:384-388.[Medline] [Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  B. Reel, G. Oktay, S. Ozkal, H. Islekel, E. Ozer, G. Ozsarlak-Sozer, Z. Cavdar, S. T. Akhisaroglu, and Z. Kerry MMP-2 and MMP-9 Alteration in Response to Collaring in Rabbits: The Effects of Endothelin Receptor Antagonism Journal of Cardiovascular Pharmacology and Therapeutics, December 1, 2009; 14(4): 292 - 301. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Dwivedi, S. C. Slater, and S. J. George MMP-9 and -12 cause N-cadherin shedding and thereby {beta}-catenin signalling and vascular smooth muscle cell proliferation Cardiovasc Res, January 1, 2009; 81(1): 178 - 186. [Abstract] [Full Text] [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. van Waveren, Y. Sun, H. S. Cheung, and C. T. Moraes Oxidative phosphorylation dysfunction modulates expression of extracellular matrix--remodeling genes and invasion Carcinogenesis, March 1, 2006; 27(3): 409 - 418. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P.G. Sluijter, D. P.V. de Kleijn, and G. Pasterkamp Vascular remodeling and protease inhibition-bench to bedside Cardiovasc Res, February 15, 2006; 69(3): 595 - 603. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Newby Matrix metalloproteinases regulate migration, proliferation, and death of vascular smooth muscle cells by degrading matrix and non-matrix substrates Cardiovasc Res, February 15, 2006; 69(3): 614 - 624. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Peterson The importance of estimating the therapeutic index in the development of matrix metalloproteinase inhibitors Cardiovasc Res, February 15, 2006; 69(3): 677 - 687. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. S. Perlstein and R. T. Lee Smoking, Metalloproteinases, and Vascular Disease Arterioscler Thromb Vasc Biol, February 1, 2006; 26(2): 250 - 256. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. G. Touchard and R. S. Schwartz Preclinical Restenosis Models: Challenges and Successes Toxicol Pathol, January 1, 2006; 34(1): 11 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Brassard, F. Amiri, G. Thibault, and E. L. Schiffrin Role of Angiotensin Type-1 and Angiotensin Type-2 Receptors in the Expression of Vascular Integrins in Angiotensin II-Infused Rats Hypertension, January 1, 2006; 47(1): 122 - 127. [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]
|
|
|
|
 |
|
 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. C. Newby Dual Role of Matrix Metalloproteinases (Matrixins) in Intimal Thickening and Atherosclerotic Plaque Rupture Physiol Rev, January 1, 2005; 85(1): 1 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. Koullias, P. Ravichandran, D. P. Korkolis, D. L. Rimm, and J. A. Elefteriades Increased Tissue Microarray Matrix Metalloproteinase Expression Favors Proteolysis in Thoracic Aortic Aneurysms and Dissections Ann. Thorac. Surg., December 1, 2004; 78(6): 2106 - 2110. [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]
|
|
|
|
 |
|
 R. S. Schwartz, N. A. Chronos, and R. Virmani Preclinical restenosis models and drug-eluting stents: Still important, still much to learn J. Am. Coll. Cardiol., October 6, 2004; 44(7): 1373 - 1385. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Frosen, A. Piippo, A. Paetau, M. Kangasniemi, M. Niemela, J. Hernesniemi, and J. Jaaskelainen Remodeling of Saccular Cerebral Artery Aneurysm Wall Is Associated With Rupture: Histological Analysis of 24 Unruptured and 42 Ruptured Cases Stroke, October 1, 2004; 35(10): 2287 - 2293. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Z. Lee, B. Xu, T. Hashimoto, C. E. McCulloch, G.-Y. Yang, and W. L. Young Doxycycline Suppresses Cerebral Matrix Metalloproteinase-9 and Angiogenesis Induced by Focal Hyperstimulation of Vascular Endothelial Growth Factor in a Mouse Model Stroke, July 1, 2004; 35(7): 1715 - 1719. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. W. Cheng, M. Kuzuya, T. Sasaki, S. Kanda, N. Tamaya-Mori, T. Koike, K. Maeda, E. Nishitani, and A. Iguchi Green tea catechins inhibit neointimal hyperplasia in a rat carotid arterial injury model by TIMP-2 overexpression Cardiovasc Res, June 1, 2004; 62(3): 594 - 602. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Jarvelainen, R. B. Vernon, M. D. Gooden, A. Francki, S. Lara, P. Y. Johnson, M. G. Kinsella, E. H. Sage, and T. N. Wight Overexpression of Decorin by Rat Arterial Smooth Muscle Cells Enhances Contraction of Type I Collagen In Vitro Arterioscler Thromb Vasc Biol, January 1, 2004; 24(1): 67 - 72. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Islam, C. D. Franco, D. W. Courtman, and M. P. Bendeck A Nonantibiotic Chemically Modified Tetracycline (CMT-3) Inhibits Intimal Thickening Am. J. Pathol., October 1, 2003; 163(4): 1557 - 1566. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kuzuya, S. Kanda, T. Sasaki, N. Tamaya-Mori, X. W. Cheng, T. Itoh, S. Itohara, and A. Iguchi Deficiency of Gelatinase A Suppresses Smooth Muscle Cell Invasion and Development of Experimental Intimal Hyperplasia Circulation, September 16, 2003; 108(11): 1375 - 1381. [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]
|
|
|
|
 |
|
 J. Herget, J. Novotna, J. Bibova, V. Povysilova, M. Vankova, and V. Hampl Metalloproteinase inhibition by Batimastat attenuates pulmonary hypertension in chronically hypoxic rats Am J Physiol Lung Cell Mol Physiol, July 1, 2003; 285(1): L199 - L208. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. B. Uglow, S. Slater, G. B. Sala-Newby, C. M. Aguilera-Garcia, G. D. Angelini, A. C. Newby, and S. J. George Dismantling of Cadherin-Mediated Cell-Cell Contacts Modulates Smooth Muscle Cell Proliferation Circ. Res., June 27, 2003; 92(12): 1314 - 1321. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M Aguilera, S. J George, J. L Johnson, and A. C Newby Relationship between type IV collagen degradation, metalloproteinase activity and smooth muscle cell migration and proliferation in cultured human saphenous vein Cardiovasc Res, June 1, 2003; 58(3): 679 - 688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B Smeets, J. P.G Sluijter, M. M.P.C Donners, E. Velema, S. Heeneman, G. Pasterkamp, and D. P.V de Kleijn Increased arterial expression of a glycosylated haptoglobin isoform after balloon dilation Cardiovasc Res, June 1, 2003; 58(3): 689 - 695. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Luan, A. J. Chase, and A. C. Newby Statins Inhibit Secretion of Metalloproteinases-1, -2, -3, and -9 From Vascular Smooth Muscle Cells and Macrophages Arterioscler Thromb Vasc Biol, May 1, 2003; 23(5): 769 - 775. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Lake, A. Bialik, K. Walsh, and J. J. Castellot Jr CCN5 Is a Growth Arrest-Specific Gene That Regulates Smooth Muscle Cell Proliferation and Motility Am. J. Pathol., January 1, 2003; 162(1): 219 - 231. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Tsukioka, J.-i. Suzuki, M. Fujimori, Y. Wada, K. Yamaura, K.-i. Ito, R. Morishita, Y. Kaneda, M. Isobe, and J. Amano Expression of matrix metalloproteinases in cardiac allograft vasculopathy and its attenuation by anti MMP-2 ribozyme gene transfection Cardiovasc Res, December 1, 2002; 56(3): 472 - 478. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Goetze, A. Bungenstock, C. Czupalla, F. Eilers, P. Stawowy, U. Kintscher, C. Spencer-Hansch, K. Graf, B. Nurnberg, R. E. Law, et al. Leptin Induces Endothelial Cell Migration Through Akt, Which Is Inhibited by PPAR{gamma}-Ligands Hypertension, November 1, 2002; 40(5): 748 - 754. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hussain, J. W. Assender, M. Bond, L.-F. Wong, D. Murphy, and A. C. Newby Activation of Protein Kinase Czeta Is Essential for Cytokine-induced Metalloproteinase-1, -3, and -9 Secretion from Rabbit Smooth Muscle Cells and Inhibits Proliferation J. Biol. Chem., July 19, 2002; 277(30): 27345 - 27352. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. Bendeck Matrix Metalloproteinases: Are They Antiatherogenic but Proaneurysmal? Circ. Res., May 3, 2002; 90(8): 836 - 837. [Full Text] [PDF]
|
|
|
|
|
|
M. P. Bendeck, M. Conte, M. Zhang, N. Nili, B. H. Strauss, and S. M. Farwell Doxycycline Modulates Smooth Muscle Cell Growth, Migration, and Matrix Remodeling after Arterial Injury Am. J. Pathol., March 1, 2002; 160(3): 1089 - 1095. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Nam, A. Moralez, and D. Clemmons Vitronectin Binding to IGF Binding Protein-5 (IGFBP-5) Alters IGFBP-5 Modulation of IGF-I Actions Endocrinology, January 1, 2002; 143(1): 30 - 36. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Cherr, S. J. Motew, J. A. Travis, J. Fingerle, L. Fisher, M. Brandl, J. K. Williams, and R. L. Geary Metalloproteinase Inhibition and the Response to Angioplasty and Stenting in Atherosclerotic Primates Arterioscler Thromb Vasc Biol, January 1, 2002; 22(1): 161 - 166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. V. Gurjar, J. DeLeon, R. V. Sharma, and R. C. Bhalla Mechanism of inhibition of matrix metalloproteinase-9 induction by NO in vascular smooth muscle cells J Appl Physiol, September 1, 2001; 91(3): 1380 - 1386. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Wentzel, J. Kloet, I. Andhyiswara, J. A. F. Oomen, J. C. H. Schuurbiers, B. J. G. L. de Smet, M. J. Post, D. de Kleijn, G. Pasterkamp, C. Borst, et al. Shear-Stress and Wall-Stress Regulation of Vascular Remodeling After Balloon Angioplasty : Effect of Matrix Metalloproteinase Inhibition Circulation, July 3, 2001; 104(1): 91 - 96. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Johnson, G. J. J. M. van Eys, G. D. Angelini, and S. J. George Injury Induces Dedifferentiation of Smooth Muscle Cells and Increased Matrix-Degrading Metalloproteinase Activity in Human Saphenous Vein Arterioscler Thromb Vasc Biol, July 1, 2001; 21(7): 1146 - 1151. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. J. Feldman, M. Mazighi, A. Scheuble, J.-F. Deux, E. De Benedetti, C. Badier-Commander, E. Brambilla, D. Henin, P. G. Steg, and M.-P. Jacob Differential Expression of Matrix Metalloproteinases After Stent Implantation and Balloon Angioplasty in the Hypercholesterolemic Rabbit Circulation, June 26, 2001; 103(25): 3117 - 3122. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bellosta, M. Canavesi, E. Favari, L. Cominacini, G. Gaviraghi, R. Fumagalli, R. Paoletti, and F. Bernini Lalsoacidipine Modulates the Secretion of Matrix Metalloproteinase-9 by Human Macrophages J. Pharmacol. Exp. Ther., March 1, 2001; 296(3): 736 - 743. [Abstract] [Full Text]
|
|
|
|
|
|
M. J. Sierevogel, G. Pasterkamp, E. Velema, P. P. T. de Jaegere, B. J. G. L. de Smet, J. H. Verheijen, D. P. V. de Kleijn, and C. Borst Oral Matrix Metalloproteinase Inhibition and Arterial Remodeling After Balloon Dilation : An Intravascular Ultrasound Study in the Pig Circulation, January 16, 2001; 103(2): 302 - 307. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Tronc, Z. Mallat, S. Lehoux, M. Wassef, B. Esposito, and A. Tedgui Role of Matrix Metalloproteinases in Blood Flow-Induced Arterial Enlargement : Interaction With NO Arterioscler Thromb Vasc Biol, December 1, 2000; 20 (12): e120 - e126. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Hampl and J. Herget Role of Nitric Oxide in the Pathogenesis of Chronic Pulmonary Hypertension Physiol Rev, October 1, 2000; 80(4): 1337 - 1372. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Vieillard-Baron, E. Frisdal, S. Eddahibi, I. Deprez, A. H. Baker, A. C. Newby, P. Berger, M. Levame, B. Raffestin, S. Adnot, et al. Inhibition of Matrix Metalloproteinases by Lung TIMP-1 Gene Transfer or Doxycycline Aggravates Pulmonary Hypertension in Rats Circ. Res., September 1, 2000; 87(5): 418 - 425. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Waugh, J. Li-Hawkins, E. Yuksel, M. D. Kuo, P. N. Cifra, P. R. Hilfiker, R. Geske, M. Chawla, J. Thomas, S. M. Shenaq, et al. Thrombomodulin Overexpression to Limit Neointima Formation Circulation, July 18, 2000; 102(3): 332 - 337. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Gonzalez, V. Fontaine, M. E. Pueyo, N. Laquay, D. Messika-Zeitoun, M. Philippe, J.-F. Arnal, M.-P. Jacob, and J.-B. Michel Molecular Plasticity of Vascular Wall During NG-Nitro-L-Arginine Methyl Ester-Induced Hypertension : Modulation of Proinflammatory Signals Hypertension, July 1, 2000; 36(1): 103 - 109. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. G. L. de Smet, D. de Kleijn, R. Hanemaaijer, J. H. Verheijen, L. Robertus, Y. J. M. van der Helm, C. Borst, and M. J. Post Metalloproteinase Inhibition Reduces Constrictive Arterial Remodeling After Balloon Angioplasty : A Study in the Atherosclerotic Yucatan Micropig Circulation, June 27, 2000; 101(25): 2962 - 2967. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. Bendeck, C. Irvin, M. Reidy, L. Smith, D. Mulholland, M. Horton, and C. M. Giachelli Smooth Muscle Cell Matrix Metalloproteinase Production Is Stimulated via {alpha}v{beta}3 Integrin Arterioscler Thromb Vasc Biol, June 1, 2000; 20(6): 1467 - 1472. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kanda, M. Kuzuya, M. A. Ramos, T. Koike, K. Yoshino, S. Ikeda, and A. Iguchi Matrix Metalloproteinase and {alpha}v{beta}3 Integrin-Dependent Vascular Smooth Muscle Cell Invasion Through a Type I Collagen Lattice Arterioscler Thromb Vasc Biol, April 1, 2000; 20(4): 998 - 1005. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Li, Y. Hu, G. Sturm, G. Wick, and Q. Xu Ras/Rac-Dependent Activation of p38 Mitogen-Activated Protein Kinases in Smooth Muscle Cells Stimulated by Cyclic Strain Stress Arterioscler Thromb Vasc Biol, March 1, 2000; 20 (3): e1 - e9. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Dietrich, Y. Hu, Y. Zou, S. Dirnhofer, R. Kleindienst, G. Wick, and Q. Xu Mouse Model of Transplant Arteriosclerosis : Role of Intercellular Adhesion Molecule-1 Arterioscler Thromb Vasc Biol, February 1, 2000; 20(2): 343 - 352. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Hou, D. Mulholland, M. A. Gronska, and M. P. Bendeck Type VIII Collagen Stimulates Smooth Muscle Cell Migration and Matrix Metalloproteinase Synthesis after Arterial Injury Am. J. Pathol., February 1, 2000; 156(2): 467 - 476. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Loscalzo Vascular Matrix and Vein Graft Failure : Is the Message in the Medium? Circulation, January 25, 2000; 101(3): 221 - 223. [Full Text] [PDF]
|
|
|
|
|
|
D. P. Mason, R. D. Kenagy, D. Hasenstab, D. F. Bowen-Pope, R. A. Seifert, S. Coats, S. M. Hawkins, and A. W. Clowes Matrix Metalloproteinase-9 Overexpression Enhances Vascular Smooth Muscle Cell Migration and Alters Remodeling in the Injured Rat Carotid Artery Circ. Res., December 3, 1999; 85(12): 1179 - 1185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. R. Lijnen, P. Soloway, and D. Collen Tissue Inhibitor of Matrix Metalloproteinases-1 Impairs Arterial Neointima Formation After Vascular Injury in Mice Circ. Res., December 3, 1999; 85(12): 1186 - 1191. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. R. Lijnen, B. Van Hoef, I. Vanlinthout, M. Verstreken, M.-C. Rio, and D. Collen Accelerated Neointima Formation After Vascular Injury in Mice With Stromelysin-3 (MMP-11) Gene Inactivation Arterioscler Thromb Vasc Biol, December 1, 1999; 19(12): 2863 - 2870. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. V. Gurjar, R. V. Sharma, and R. C. Bhalla eNOS Gene Transfer Inhibits Smooth Muscle Cell Migration and MMP-2 and MMP-9 Activity Arterioscler Thromb Vasc Biol, December 1, 1999; 19(12): 2871 - 2877. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Johnson and A. Knox Autocrine production of matrix metalloproteinase-2 is required for human airway smooth muscle proliferation Am J Physiol Lung Cell Mol Physiol, December 1, 1999; 277(6): L1109 - L1117. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Southgate, D. Mehta, M. B. Izzat, A. C. Newby, and G. D. Angelini Increased Secretion of Basement Membrane–Degrading Metalloproteinases in Pig Saphenous Vein Into Carotid Artery Interposition Grafts Arterioscler Thromb Vasc Biol, July 1, 1999; 19(7): 1640 - 1649. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. D. Foda, S. George, E. Rollo, M. Drews, C. Conner, J. Cao, R. A. Panettieri Jr., and S. Zucker Regulation of gelatinases in human airway smooth muscle cells: mechanism of progelatinase A activation Am J Physiol Lung Cell Mol Physiol, July 1, 1999; 277(1): L174 - L182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Plenz, A. Dorszewski, G. Breithardt, and H. Robenek Expression of Type VIII Collagen After Cholesterol Diet and Injury in the Rabbit Model of Atherosclerosis Arterioscler Thromb Vasc Biol, May 1, 1999; 19(5): 1201 - 1209. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. A. Giese, M. M. H. Marijianowski, O. McCook, A. Hancock, V. Ramakrishnan, L. J. Fretto, C. Chen, A. B. Kelly, J. A. Koziol, J. N. Wilcox, et al. The Role of Alpha and Beta Platelet-Derived Growth Factor Receptor in the Vascular Response to Injury in Nonhuman Primates Arterioscler Thromb Vasc Biol, April 1, 1999; 19(4): 900 - 909. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Furukawa, A. Matsumori, N. Ohashi, T. Shioi, K. Ono, A. Harada, K. Matsushima, and S. Sasayama Anti–Monocyte Chemoattractant Protein-1/Monocyte Chemotactic and Activating Factor Antibody Inhibits Neointimal Hyperplasia in Injured Rat Carotid Arteries Circ. Res., February 19, 1999; 84(3): 306 - 314. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kranzhofer, A. H. Baker, S. J. George, and A. C. Newby Expression of Tissue Inhibitor of Metalloproteinase-1, -2, and -3 During Neointima Formation in Organ Cultures of Human Saphenous Vein Arterioscler Thromb Vasc Biol, February 1, 1999; 19(2): 255 - 265. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C Newby and A. B Zaltsman Fibrous cap formation or destruction -- the critical importance of vascular smooth muscle cell proliferation, migration and matrix formation Cardiovasc Res, February 1, 1999; 41(2): 345 - 360. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Jones, F. Jones, B Zhou, and M Rabinovitch Induction of vascular smooth muscle cell tenascin-C gene expression by denatured type I collagen is dependent upon a beta3 integrin-mediated mitogen-activated protein kinase pathway and a 122-base pair promoter element J. Cell Sci., January 2, 1999; 112(4): 435 - 445. [Abstract] [PDF]
|
|
|
|
|
|
S. Bellosta, D. Via, M. Canavesi, P. Pfister, R. Fumagalli, R. Paoletti, and F. Bernini HMG-CoA Reductase Inhibitors Reduce MMP-9 Secretion by Macrophages Arterioscler Thromb Vasc Biol, November 1, 1998; 18(11): 1671 - 1678. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Topol and P. W. Serruys Frontiers in Interventional Cardiology Circulation, October 27, 1998; 98(17): 1802 - 1820. [Full Text] [PDF]
|
|
|
|
|
|
H. Wang and J. A. Keiser Vascular Endothelial Growth Factor Upregulates the Expression of Matrix Metalloproteinases in Vascular Smooth Muscle Cells : Role of flt-1 Circ. Res., October 19, 1998; 83(8): 832 - 840. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Janiszewski, C. A Pasqualucci, L. C Souza, F. Pileggi, P. L da Luz, and F. R M. Laurindo Oxidized thiols markedly amplify the vascular response to balloon injury in rabbits through a redox active metal-dependent pathway Cardiovasc Res, August 1, 1998; 39(2): 327 - 338. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. S. Bassiouny, R. H. Song, X. F. Hong, A. Singh, H. Kocharyan, and S. Glagov Flow Regulation of 72-kD Collagenase IV (MMP-2) After Experimental Arterial Injury Circulation, July 14, 1998; 98(2): 157 - 163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Kenagy, C. E. Hart, W. G. Stetler-Stevenson, and A. W. Clowes 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 Circulation, November 18, 1997; 96(10): 3555 - 3560. [Abstract] [Full Text]
|
|
|
|
|
|
S. J. George, J. L. Johnson, G. D. Angelini, and J. Y. Jeremy Short-term Exposure to Thapsigargin Inhibits Neointima Formation in Human Saphenous Vein Arterioscler Thromb Vasc Biol, November 1, 1997; 17(11): 2500 - 2506. [Abstract] [Full Text]
|
|
|
|
|
|
J. G. Pickering, S. Uniyal, C. M. Ford, T. Chau, M. A. Laurin, L. H. Chow, C. G. Ellis, J. Fish, and B. M. C. Chan Fibroblast Growth Factor-2 Potentiates Vascular Smooth Muscle Cell Migration to Platelet-Derived Growth Factor : Upregulation of {alpha}2ß1 Integrin and Disassembly of Actin Filaments Circ. Res., May 19, 1997; 80(5): 627 - 637. [Abstract] [Full Text]
|
|
|
|
|
|
A. Hultgardh-Nilsson, C. Lovdahl, K. Blomgren, Bengt Kallin, and J. Thyberg Expression of phenotype- and proliferation-related genes in rat aortic smooth muscle cells in primary culture Cardiovasc Res, May 1, 1997; 34(2): 418 - 430. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. R. Moreno, V. H. Bernardi, J. Lopez-Cuellar, J. B. Newell, C. McMellon, H. K. Gold, I. F. Palacios, V. Fuster, and J. T. Fallon Macrophage Infiltration Predicts Restenosis After Coronary Intervention in Patients With Unstable Angina Circulation, December 15, 1996; 94(12): 3098 - 3102. [Abstract] [Full Text]
|
|
|
|
|
|
R.D. Kenagy, S. Vergel, E. Mattsson, M. Bendeck, M.A. Reidy, and A.W. Clowes The Role of Plasminogen, Plasminogen Activators, and Matrix Metalloproteinases in Primate Arterial Smooth Muscle Cell Migration Arterioscler Thromb Vasc Biol, November 1, 1996; 16(11): 1373 - 1382. [Abstract] [Full Text]
|
|
|
|
|
|
R. Forough, N. Koyama, D. Hasenstab, H. Lea, M. Clowes, S. T. Nikkari, and A. W. Clowes Overexpression of Tissue Inhibitor of Matrix Metalloproteinase-1 Inhibits Vascular Smooth Muscle Cell Functions In Vitro and In Vivo Circ. Res., October 1, 1996; 79(4): 812 - 820. [Abstract] [Full Text]
|
|
|
|
|
|
S. Eguchi, P. J. Dempsey, G. D. Frank, E. D. Motley, and T. Inagami Activation of MAPKs by Angiotensin II in Vascular Smooth Muscle Cells. METALLOPROTEASE-DEPENDENT EGF RECEPTOR ACTIVATION IS REQUIRED FOR ACTIVATION OF ERK AND p38 MAPK BUT NOT FOR JNK J. Biol. Chem., March 9, 2001; 276(11): 7957 - 7962. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Chassagne, C. Adamy, P. Ratajczak, B. Gingras, E. Teiger, E. Planus, P. Oliviero, L. Rappaport, J.-L. Samuel, and S. Meloche Angiotensin II AT2 receptor inhibits smooth muscle cell migration via fibronectin cell production and binding Am J Physiol Cell Physiol, April 1, 2002; 282(4): C654 - C664. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-S. Silvestre, Z. Mallat, R. Tamarat, M. Duriez, A. Tedgui, and B. I. Levy Regulation of Matrix Metalloproteinase Activity in Ischemic Tissue by Interleukin-10: Role in Ischemia-Induced Angiogenesis Circ. Res., August 3, 2001; 89(3): 259 - 264. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||