© 1999 American Heart Association, Inc.
Vascular Biology |
Role of Matrix Metalloproteinases and Their Tissue Inhibitors in the Regulation of Coronary Cell Migration
From the Cardiovascular Research Center, Department of Medicine (Cardiology) (Y.S., S.P., R.N., W.C., A.Z.) and Department of Physiology (P.D.), Thomas Jefferson University, Philadelphia, Pa.
Correspondence to Yi Shi, Thomas Jefferson University, Cardiovascular Research Center, Division of Cardiology, Suite 403D, 1025 Walnut Street, Philadelphia, PA 19107. E-mail yi.shi{at}mail.tju.edu
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Abstract |
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Abstract—The migration of vascular cells is regulated by matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). Because the activation of adventitial fibroblasts has been implicated in coronary repair, we have examined regional differences in cell outgrowth and the synthesis of MMPs/TIMPs in different layers of porcine coronary arteries. Coronary medial explants demonstrated significantly slower cell outgrowth than coronary adventitia in culture (P<0.001). These observations were paralleled by the predominant expression of TIMP-1 and -2 in the media (14-fold and 37-fold higher than in adventitia, respectively, P<0.001), whereas higher gelatinolytic activities (MMP-2 and -9) were released from adventitial explants. Smooth muscle cell outgrowth from the media was regulated by endogenous TIMPs, since TIMP inhibition (recombinant MMP-2 or neutralizing anti-TIMP antibodies) facilitated cell outgrowth (P<0.001). In contrast, the addition of recombinant TIMP-1 or -2 decreased adventitial cell outgrowth. In the coculture experiments, the presence of coronary media retarded adventitial cell outgrowth, whereas medial damage abrogated these effects, allowing for fibroblast migration (P<0.001). In conclusion, this study demonstrated differential migratory properties and distinct MMP/TIMP synthesis by coronary fibroblasts and smooth muscle cells. Endogenous TIMPs in the media may play an important role in maintaining coronary arterial wall homeostasis, whereas high levels of matrix-degrading activities confer the "invasive" characteristics of adventitial fibroblasts.
Key Words: migration • matrix metalloproteinases • tissue inhibitor of matrix metalloproteinase • fibroblasts • smooth muscle cells
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Introduction |
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Abalance between matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) contributes to tissue remodeling under physiological and pathological conditions.1 2 3 4 Migration of resident vascular cells, a key event in the development of many vascular diseases,5 is associated with enzymatic degradation of the intricate network of extracellular matrix (ECM) proteins. The upregulation of MMPs and serine proteases coincides with the formation of a hypercellular neointima after arterial injury.6 7 8 9 Previous studies have emphasized the expression of proteolytic enzymes by smooth muscle (SM) cells, which is consistent with the migration of medial cells during remodeling of noncoronary vascular beds.10 11 12 13 14 Recent observations regarding coronary response to injury, however, have pointed to a number of cellular mechanisms not included in the classic paradigm of vascular repair.15 They involved the phenotypic versatility of adventitial fibroblasts that contribute to coronary repair,16 17 similar to nonvascular fibroblasts during wound healing.18 19 Translocation of coronary adventitial fibroblasts/myofibroblasts to the neointima contrasted with a limited response of medial SM cells in a porcine model of severe coronary injury.20 21 These observations have prompted a question regarding the mechanisms regulating distinctive properties of cellular constituents within the coronary arterial wall. In this study, we sought to examine whether the migratory characteristics of adventitial and medial coronary cells are mediated by regional differences in the expression of matrix-degrading enzymes and their tissue inhibitors. The results demonstrated a higher intrinsic gelatinolytic activity and a rapid cell outgrowth in the adventitia, whereas preferential expression of TIMPs was present in the media that exhibited slower cell outgrowth. Endogenous TIMPs had the ability to inhibit adventitial cell outgrowth, whereas the inactivation of TIMPs in the media promoted cell migration. These findings suggest that constitutive expression of TIMPs in coronary media plays an important regulatory role in arterial wall homeostasis.
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Methods |
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Preparation of Explants and Cell Outgrowth
Coronary arteries derived from domestic crossbred female pigs (4 to 6 months old) were longitudinally opened and the endothelium was removed by gentle rubbing. The adventitia and media were separated by using fine surgical instruments with the assistance of surgical loops (magnification x2) followed by
-SM actin immunostaining of random samples (not
shown). Cell outgrowth assay was performed by using a modified method
described by Kenagy et al.13 The adventitia and media were
first cut into 1-mm strips and then into 
1-mm2
pieces. They were plated into individual wells of a 24-well plate in
DMEM supplemented with 10% FBS, 100 IU/mL penicillin, 100 µg/mL
streptomycin, and 2 mmol/L glutamine at 37°C in a
humidified incubator with 5% CO2. In some
experiments, medial explants were placed in wells coated with either
matrigel, fibronectin, laminin, collagen type I, or collagen type IV or
were stimulated with platelet-derived growth
factor-BB (PDGF-BB) (10 ng/mL) or interleukin-1 (1 ng/mL) to
facilitate SM cell outgrowth. For the coculture experiments,
adventitial explants (1 mm2) were placed
on top of the media (2 mm2). Fresh medium
was added every 2 days. The explants were examined daily under a
microscope and counted as positive for migration if 
5 cells were
observed. Five cells rather than 1 cell were used to determine cell
outgrowth to eliminate false-positive results because of tissue
manipulation. The time to achieve outgrowth in 50% of the explants was
calculated, because coronary media never reached migration in
all explants over the 20-day period. To evaluate the regulation of
coronary cell outgrowth, recombinant MMP-2, TIMP-1 and -2, and
neutralizing antibodies against TIMP-1 and -2 (Calbiochem) were added
at different concentrations to the culture medium. Irrelevant protein
(mouse IgG) was used as a control for TIMP neutralizing antibodies.
Each experiment was performed in 6 explants per condition and was
repeated 3 to 12 times on different occasions, using tissues isolated
from at least 3 animals.
Preparation of Conditioned Medium From Coronary Tissue
Explants
To measure the changes in MMPs and TIMPs in tissue explants,
multiple coronary adventitial or medial specimens (15 to 20
explants) derived from at least 2 coronary arteries were placed
in a serum-free medium (0.5 mL/well) for 24 hours. For stimulation, the
explants were placed on a metal screen in 10% FBS for 3 days. After
rinsing with a serum-free medium, the explants were transferred into
24-well plates and incubated in a serum-free medium for an additional
24 hours (0.5 mL/well). The conditioned medium from explants was
harvested after the addition of PMSF (1 mmol/L, Sigma). After
centrifugation, the supernatant was concentrated 5x
through a Centricon concentrator 10 (Amicon) and stored in
aliquots at -70°C. The protein concentration was measured with BSA
as a standard (Bio-Rad Laboratories).
Zymography
Gelatinolytic activity was analyzed
by zymography with bovine skin gelatin or ß-casein (1 mg/mL, Sigma)
as substrate.22 The conditioned medium from tissue
explants (15 µg of protein per lane) was electrophoresed at 4°C in
7.5% (wt/vol) polyacrylamide gels containing 0.2% SDS under a
nondenaturing condition. After electrophoresis, the gels were washed in
1% Triton X-100 and then incubated at 37°C in 50 mmol/L Tris
buffer (pH 7.6) containing 5 mmol/L
CaCl2, 1 µmol/L
ZnCl2, 1 mmol/L aminophenolmercuric acetate,
and 1% Triton X-100 for 18 hours. The gels were stained with Coomassie
Brilliant Blue R-250 (Sigma) in 5% acetic acid and 10% ethanol.
Gelatinolytic or caseinolytic activities were
indicated by clear zones of lysis with MMP-2 (Calbiochem) and MMP-9
(Chemicon) used as standards. Identical gels were incubated in the
presence of 10 mmol/L EDTA to confirm the metal dependence of
gelatinolytic activity that is characteristic of
MMPs.22 The gels were dried, scanned by a ScanJet 4C
scanner (Hewlett Packard), and analyzed by using NIH Image
1.61/ppc software. Each experiment was performed at least 4 times on
different occasions by using tissue isolated from at least 8
animals.
Western Blot
To identify MMPs and TIMPs, the antibodies from at least 2
independent sources were used. The conditioned medium was
electrophoresed on 4% to 15% (wt/vol) Tris-glycine ready gel (Bio-Rad
Laboratories). The fractionated proteins were then electrotransferred
onto PolyScreen PVDF membranes (DuPont NEN) in a transfer buffer
containing 192 mmol/L glycine, 25 mmol/L Tris, 0.01% SDS,
and 20% methanol. The blots were blocked in 5% nonfat milk for 1 hour
and then incubated with mouse monoclonal antibodies or rabbit
polyclonal antibodies against human MMP-2 and 9 (Binding Site and
Calbiochem), and human TIMP-1 and -2 (Calbiochem and Chemicon) in 2.5%
BSA. Positive controls included human MMPs and TIMPs (Calbiochem and
Chemicon). The membranes were washed 3 times with PBS containing 0.1%
Tween 20 and incubated with biotinylated goat anti-mouse or goat
anti-rabbit antibodies. The blots were washed and then incubated with
streptavidin–peroxidase conjugate (Boehringer Mannheim) for 30
minutes. After washing, the blots were incubated with Renaissance
chemiluminescence reagent (DuPont NEN) for 10 seconds and exposed to
Kodak X-Omat film for 30 seconds to 3 minutes. The films were scanned
and analyzed as described above. Each experiment was performed
at least 3 times on different occasions by using tissues isolated from
at least 6 animals.
Statistical Analysis
Data are expressed as mean±SD values. Paired t test
was used to compare the difference between paired samples. One-way
ANOVA was used to compare the multigroup variables. If the
F test results were significant, Bonferroni's
analysis was performed to determine differences among
subgroups. A value of P<0.05 was required to reject the
null hypothesis.
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Results |
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Cell Outgrowth From Coronary Adventitia and Media
To examine migration of the cellular constituents of the arterial wall, we have compared cell outgrowth from porcine coronary adventitial and medial explants. The time to reach migration (ie,
5 cells) in 50% of serum-stimulated explants was
12±2 days and 3±1 days for medial and adventitial samples (n=12,
P<0.001), respectively. Although medial cell outgrowth was
facilitated by addition of PDGF-BB (10±1 days, n=4, P<0.01
versus serum-stimulated media), their migratory properties remained
slower than those of adventitial fibroblasts (P<0.001).
Furthermore, additional stimuli (interleukin-1, n=4) or various
matrix components (fibronectin, matrigel, collagen I, collagen IV, and
laminin; n=4) failed to enhance the outgrowth of coronary SM
cells (Figure 1
). Cell outgrowth was
independent of cell proliferation, inasmuch as the addition of
hydroxyurea (5 mmol/L) for 15 days, an inhibitor of
DNA synthesis, did not affect cell migration from coronary
explants (12±2 days and 3±1 days, respectively, for medial and
adventitial explants, n=3, NS versus no hydroxyurea).
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P<0.001, control adventitia versus media cultured in
all other conditions.
Matrix-Degrading Activity and TIMPs in Coronary Adventitial
and Medial Explants
To examine the synthesis of matrix-degrading enzymes,
gelatinolytic activities in the conditioned medium
derived from coronary medial and adventitial explants were
compared by zymography. Medial explants exhibited lower levels of MMP-2
(66 kDa and 72 kDa) and MMP-9 (88 kDa), compared with
adventitial samples (n=5, P<0.01; Figure 2). The expression of MMP-2 (72 kDa and
66 kDa) was confirmed by Western blot, whereas MMP-9 antibodies
failed to recognize porcine MMP-9 (data not shown).
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The expression of TIMPs was examined in the conditioned medium from
coronary explants by Western blot. TIMP-1 and -2 were
predominantly synthesized by the media, which showed 14-fold (n=8) and
37-fold (n=3) higher levels over the adventitia, respectively
(P<0.001; Figure 3). An
unknown species (55 kDa) was also recognized by polyclonal TIMP-2
antibody in coronary adventitia. After serum stimulation,
TIMP-1 levels remained high in coronary media, whereas TIMP-2
expression decreased. In contrast, the levels of TIMP-1 and -2 did not
increase in serum-stimulated adventitial explants (data not shown).
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Modulation of Coronary Cell Outgrowth by MMPs and
TIMPs
Regional differences in cell outgrowth (Figure 1
) and
MMP/TIMP levels (Figures 2 and 3) suggested a causal relation
between these phenomena. The functional importance of a high
gelatinolytic activity within the adventitia was
examined in the inhibition experiments by using recombinant TIMP-1 and
-2. Both recombinant TIMPs significantly delayed adventitial cell
outgrowth (Figure 4; n=3,
P<0.001). Conversely, the role of higher TIMP levels in
coronary media was assessed by using recombinant MMP-2 or
neutralizing antibodies against TIMP-1 or -2. SM cell outgrowth from
coronary medial explants was enhanced by all treatments
designed to abolish endogenous TIMPs (Figure 5; n=3, P<0.01), although the
rate of migration remained lower than that for adventitial cells.
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Higher levels of TIMP expression in coronary media
suggested a potential homeostatic mechanism preventing cell outgrowth
in the coronary vasculature. To test the effects of
endogenous TIMPs, coronary media was cocultured
with adventitia to examine adventitial cell outgrowth (Figure 6). The presence of normal
coronary media inhibited adventitial cell outgrowth similar to
recombinant TIMPs applied to the adventitia (Figure 4). This
inhibitory effect was likely mediated by a secretable
factor(s) (eg, endogenous TIMPs), because medial damage
(boiling) restored adventitial fibroblast outgrowth (Figure 6;
n=4, P<0.001).
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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This study presents evidence for regional differences in the balance between MMPs and TIMPs within the coronary arterial wall. Coronary media showed constitutive expression of TIMPs, low levels of gelatinolytic activity, and a slow cell outgrowth. In contrast, the adventitial layer exhibited preferential matrix-degrading activity associated with a rapid cell outgrowth. Endogenous TIMPs suppressed coronary cell outgrowth, which suggested their regulatory role in maintaining coronary arterial wall homeostasis.
Coronary Cell Migration and MMPs/TIMPs
Cell migration in vivo is facilitated by the chemotactant effects
of cytokines, cytoskeletal proteins allowing for cell
locomotion, and degradation of ECM. Adventitial fibroblasts undergo
changes in their cytoskeleton (myofibroblast formation) and translocate
to the neointima after severe coronary
injury.16 17 20 21 23 The latter is often obscured by the
similarities between activated fibroblasts (ie, myofibroblasts)
and the adjacent SM cells. The present study has largely avoided
these difficulties by using arterial explants as described
by Kenagy et al.13 Cell outgrowth from adventitial and
medial explants reflected the intrinsic ability of cells to migrate and
local differences in ECM composition. The effects of cell proliferation
was minimized by counting the explants positive for migration rather
than the absolute cell number. The observed differences in migratory
properties of adventitial and medial cells corroborated previous
findings in vivo, which suggested the involvement of coronary
fibroblasts in neointimal formation.17 20 21
Vascular fibroblasts have also been implicated in intimal formation in
porcine arterialized saphenous vein grafts and in canine
carotid arteries after mild injury.24 25 Species
differences or vascular cell heterogeneity could
account for fewer than expected migratory properties of
coronary SM cells as noted in this study.26 27 28 29
These factors could also play a role in purported
inhibitory influence of the adventitia on medial cell
migration previously described in noncoronary vascular tissues
of rabbits.28
The activation of MMPs and serine proteases is required for vascular
cells to breach the surrounding ECM. Although the increases in the
overall gelatinolytic activities have been
previously detected after noncoronary arterial
injury (rat, pig, and baboon),6 7 13 14 30 local
matrix-degrading homeostasis in the coronary vasculature has been less
elucidated. The expression of MMPs/TIMPs is regulated by several
growth factors and cytokines that are locally released after
vascular injury.7 12 31 At the transcriptional level,
cytokines act through the positive or negative regulatory
elements of MMPs/TIMPs genes.32 At the posttranscriptional
level, the activation of MMPs involves plasmin-dependent cleavage of
its propeptide and membrane-type MMP, which exerts local tissue control
of MMP-2.33 34 In this study, different levels of
MMPs/TIMPs were released from adventitial explants (Figures 2 and 3). Higher expression of TIMPs in coronary media was
associated with limited outgrowth of medial SM cells, despite the
concomitant decrease in TIMP-2, likely caused by its binding with MMP-2
after stimulation. In contrast, significantly higher MMP activity in
the adventitia was associated with "invasive" properties of
adventitial fibroblasts. The causal relation between MMPs/TIMPs and
coronary cell migration has been further suggested by several
blocking experiments that targeted either endogenous TIMPs
in the media or MMPs in the adventitia (Figures 4 and 5).
TIMPs and Vessel Wall Homeostasis
Local expression of TIMPs exerts broad biological functions,
including the regulation of ECM turnover, the modulation of growth
factor activity, and the effect on cell morphology.35 The
constitutive expression of TIMP-1 and -2 in the tunica media may
represent an important mechanism maintaining vessel wall
homeostasis. Our observations suggest that endogenous TIMPs
retard vascular cell migration consistent with the reduction of
neointimal formation after overexpression of TIMP-1 in the
injured rat carotid artery.36 The inhibitors
of MMPs, interacting either directly (eg, TIMP-1 and -2) or through
serine proteases (eg, PAI-1), increase in the neointima
after arterial injury.37 38 Their biological
effects are not restricted to the regulation of cell migration (TIMP-1,
-2, and -3), but they also exert an antiproliferative effect (TIMP-2)
or induce apoptosis (TIMP-3) when overexpressed.39
The homeostatic role of the intact media has been exemplified by
the inhibition of adventitial cell outgrowth in the coculture
experiments (Figure 6). The mechanism of this phenomenon likely
involved endogenous TIMPs produced by the media, because
depletion of TIMPs from the media (boiling) allowed for adventitial
cell outgrowth, whereas recombinant TIMPs retarded adventitial cell
outgrowth. The age-dependent loss of TIMP-1 expression could contribute
to altered arterial homeostasis and increased intimal
formation during aging.40 It remains to be determined
whether focal medial damage is accompanied by further reduction in TIMP
synthesis and contributes to the observed shift toward ECM degradation
in atherosclerotic lesions.3 41
In conclusion, the results of this study demonstrated that the differences in migratory properties of coronary fibroblasts and SM cells are associated with dissimilar levels of MMPs/TIMPs. Slow migration of coronary SM cells is likely caused by constitutive expression of TIMPs and low expression of MMPs, whereas higher levels of matrix-degrading activity may confer invasive characteristics of adventitial fibroblasts. Our findings suggest that endogenous TIMPs in the media play an important role in maintaining arterial homeostasis (eg, preventing coronary cell migration) and that the impairment of their synthesis may contribute to the pathogenesis of coronary lesion formation.
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Acknowledgments |
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This study was supported in part by grants from the National Institutes of Health (HL-44150 and HL-60672) (to A.Z. and Y.S.).
Received July 31, 1998; accepted September 26, 1998.
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References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Brenner CA, Adler RR, Rappolee DA, Pedersen RA, Werb Z. Genes for extracellular matrix-degrading metalloproteinases and their inhibitor, TIMP, are expressed during early mammalian development. Genes Dev. 1989;3:848–859.
2.
Dollery CM, McEwan JR, Henney AM. Matrix
metalloproteinases and cardiovascular disease.
Circ Res. 1995;77:863–868.
3. 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.
4.
McMillan WD, Patterson BK, Keen RR, Shively VP,
Cipollone M, Pearce WH. In situ localization and quantification of mRNA
for 92-kD type IV collagenase and its inhibitor
in aneurysmal, occlusive, and normal aorta. Arterioscler
Thromb Vasc Biol. 1995;15:1139–1144.
5.
Schwartz SM, deBlois D, O'Brien ERM. The intima: soil
for atherosclerosis and restenosis. Circ
Res. 1995;77:445–465.
6. 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]
7.
Southgate KM, Fisher M, Banning AP, Thurston VJ, Baker
AH, Fabunmi RP, Groves PH, Davies M, Newby AC. Upregulation of basement
membrane-degrading metalloproteinase secretion after balloon injury of
pig carotid arteries. Circ Res. 1996;79:1177–1187.
8.
Clowes AW, Clowes MM, Au YPT, Reidy MA, Belin D.
Smooth muscle express urokinase during mitogenesis and tissue-type
plasminogen activator during migration in
injured rat carotid artery. Circ Res. 1990;67:61–67.
9.
Reidy MA, Irvin C, Lindner V. Migration of
arterial wall cells: expression of plasminogen
activators and inhibitors in injured rat
arteries. Circ Res. 1996;78:405–414.
10.
Galis ZS, Muszynski M, Sukhova GK, Simon-Morrissey E,
Unemori EN, Lark MW, Mento E, Libby P. Cytokine-stimulated
human vascular smooth muscle cells synthesize a complement of enzymes
required for extracellular matrix digestion. Circ Res. 1994;75:181–189.
11.
Pauly RR, Passanity A, Bilato C, Monticone R, Cheng L,
Papadopoulos N, Yehezkiel AG, 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.
12. 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;315:335–342.
13.
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;16:1373–1382.
14.
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.
15.
Zalewski A, Shi Y. Vascular myofibroblasts. Lessons
from coronary repair and remodeling. Arterioscler Thromb
Vasc Biol. 1997;17:417–422.
16.
Shi Y, Pieniek M, Fard A, O'Brien J, Mannion JD,
Zalewski A. Adventitial remodeling following coronary
arterial injury. Circulation. 1996;93:340–348.
17.
Shi Y, O'Brien JE Jr, Ala-Kokko L, Chung W, Mannion
JD, Zalewski A. Origin of extracellular matrix synthesis during
coronary repair. Circulation. 1997;95:997–1006.
18.
Darby I, Skalli O, Gabbiani G. -Smooth muscle
actin is transiently expressed in by myofibroblasts during experimental
wound healing. Lab Invest. 1990;63:21–29.[Medline]
[Order article via Infotrieve]
19. Salo T, Mäkelä M, Kylmäniemi M, Autio-Harmainen H, Larjava H. Expression of matrix metalloproteinase-2 and -9 during early human wound healing. Lab Invest. 1994;70:176–182.[Medline] [Order article via Infotrieve]
20.
Shi Y, O'Brien JE Jr, Fard A, Mannion JD, Wang D,
Zalewski A. Adventitial myofibroblasts contribute to
neointimal formation in injured porcine coronary
arteries. Circulation. 1996;94:1655–1664.
21.
Scott NA, Cipolla GD, Ross CE, Dunn B, Martin FH,
Simonet L, Wilcox JN. Identification of a potential role for the
adventitia in vascular lesion formation after balloon overstretch
injury of porcine coronary arteries. Circulation. 1996;93:2178–2187.
22.
Hibbs MS. Hasty KA, Seyer JM, Kang AH, Mainardi CL.
Biological and immunological characterization of the secreted forms of
human neutrophil gelatinase. J Biol Chem. 1985;260:2493–2500.
23.
Shi Y, O'Brien JE, Fard A, Zalewski A. Transforming
growth factor ß1 expression and myofibroblast formation during
arterial repair. Arterioscler Thromb Vasc Biol. 1996;16:1298–1305.
24.
Shi Y, O'Brien JE, Mannion JD, Morrison RC, Chung W,
Fard A, Zalewski A. Remodeling of autologous saphenous vein grafts: the
role of perivascular myofibroblasts. Circulation. 1997;95:2684–2693.
25. Holifield B, Helgason T, Jemelka S, Taylor A, Navran S, Allen J, Seidel C. Differentiated vascular myocytes: are they involved in neointimal formation? J Clin Invest. 1996;97:814–825.[Medline] [Order article via Infotrieve]
26. 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]
27.
Clowes AW, Schwartz SM. Significance of quiescent
smooth muscle migration in the injured rat carotid artery. Circ
Res. 1985;56:139–145.
28. Betz E, Fallier-Becker P, Wolburg-Buchholz K, Fotev Z. Proliferation of smooth muscle cells in the inner and outer layers of the tunica media of arteries: an in vitro study. J Cell Physiol. 1991;147:385–395.[Medline] [Order article via Infotrieve]
29.
Seidel CL, Helgason T, Allen JC, Wilson C. Migratory
abilities of different vascular cells from the tunica media of canine
vessels. Am J Physiol. 1997;272:C847–C852.
30.
Jenkins GM, Crow MT, Bilato C, Gluzband Y, Ryu WS,
Li ZH, Stetler-Stevenson W, Nater C, Froehlich JP, Lakatta EG,
Cheng L. Increased expression of membrane-type matrix metalloproteinase
and preferential localization of matrix metalloproteinase-2 to the
neointima of balloon-injured rat carotid arteries.
Circulation. 1998;97:82–90.
31.
Kenagy RD, Hart CE, Stetler-Stevenson WG, Clowes
AW. 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. 1997;96:3555–3560.
32. Ries C, Petrides PE. Cytokine regulation of matrix metalloproteinase activity and its regulatory dysfunction in disease. Biol Chem. 1995;376:345–355.
33. Keski-Oja J, Lohi J, Tuuttila A, Tryggvason K, Vartio T. Proteolytic processing of the 72,000-Da type IV collagenase by urokinase plasminogen activator. Exp Cell Res. 1992;202:471–476.[Medline] [Order article via Infotrieve]
34. Sato H, Takino T, Okada Y, Cao J, Shingawa A, Yamamoto E, Seiki M. A matrix metalloproteinase expressed on the surface of invasive tumor cells. Nature. 1994;370:61–65.[Medline] [Order article via Infotrieve]
35. Gomez DE, Alonso DE, Yoshiji H, Thorgeirsson UP. Tissue inhibitors of metalloproteinase: structure, regulation and biological functions. Eur J Cell Biol. 1997;74:111–122.[Medline] [Order article via Infotrieve]
36.
Forough R, Koriyuki N, Hasenstab D, Lea H, Clowes M,
Nikkari ST, Clowes AW. Overexpression of tissue inhibitor
of matrix metalloproteinase-1 inhibits vascular smooth muscle cell
functions in vitro and in vivo. Circ Res. 1996;79:812–820.
37. Wang H, Moore S, Alavi MZ. Synthesis of tissue inhibitor of metalloproteinase-1 (TIMP-1) in rabbit aortic neointima after selective de-endothelialization. Atherosclerosis. 1996;126:95–104.[Medline] [Order article via Infotrieve]
38.
Hasenstab D, Forough R, Clowes AW.
Plasminogen activator inhibitor
type 1 and tissue inhibitor of metalloproteinases-2
increase after arterial injury in rats. Circ
Res. 1997;80:490–496.
39. Baker AH, Zalsman AB, George SJ, Newby AC. Divergent effects of tissue inhibitor of metalloproteinase-1, -2, or -3 overexpression on rat vascular smooth muscle cell invasion, proliferation, and death in vitro. J Clin Invest. 1998;101:1478–1487.[Medline] [Order article via Infotrieve]
40. Ashcroft GS, Herrick SE, Tarnuzzer RW, Horan MA, Schultz GS, Ferguson MWJ. Human ageing impairs injury-induced in vivo expression of tissue inhibitor of matrix metalloproteinases (TIMP)-1 and -2 proteins and mRNA. J Pathol. 1997;183:169–176.[Medline] [Order article via Infotrieve]
41. Li ZH, Li L, Zielke R, Cheng L, Xiao R, Crow MT, Stetler WG, Froehlich J, Lakatta EG. Increased expression of 72-kd type IV collagenase (MMP-2) in human aortic atherosclerotic lesions. Am J Pathol. 1996;148:121–128.[Abstract]
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 S. Misra, A. A. Fu, K. D. Misra, J. F. Glockner, and D. Mukhopadhyay Wall Shear Stress Measurement Using Phase Contrast Magnetic Resonance Imaging With Phase Contrast Magnetic Resonance Angiography in Arteriovenous Polytetrafluoroethylene Grafts Angiology, August 1, 2009; 60(4): 441 - 447. [Abstract] [PDF]
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 C. M. Mallawaarachchi, P. L. Weissberg, and R. C. M. Siow Antagonism of platelet-derived growth factor by perivascular gene transfer attenuates adventitial cell migration after vascular injury: new tricks for old dogs? FASEB J, August 1, 2006; 20(10): 1686 - 1688. [Abstract] [Full Text] [PDF]
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 K. R. Stenmark, N. Davie, M. Frid, E. Gerasimovskaya, and M. Das Role of the Adventitia in Pulmonary Vascular Remodeling Physiology, April 1, 2006; 21(2): 134 - 145. [Abstract] [Full Text] [PDF]
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 L.-N. Zhang, D. W. Wilson, V. da Cunha, M. E. Sullivan, R. Vergona, J. C. Rutledge, and Y.-X. Wang Endothelial NO Synthase Deficiency Promotes Smooth Muscle Progenitor Cells in Association With Upregulation of Stromal Cell-Derived Factor-1{alpha} in a Mouse Model of Carotid Artery Ligation Arterioscler Thromb Vasc Biol, April 1, 2006; 26(4): 765 - 772. [Abstract] [Full Text] [PDF]
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C. M. Mallawaarachchi, P. L. Weissberg, and R. C.M. Siow Smad7 Gene Transfer Attenuates Adventitial Cell Migration and Vascular Remodeling After Balloon Injury Arterioscler Thromb Vasc Biol, July 1, 2005; 25(7): 1383 - 1387. [Abstract] [Full Text] [PDF]
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 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]
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 C. L Burns-Kurtis, A. R Olzinski, S. Needle, J. H Fox, E. A Capper, F. M Kelly, M. S McQueney, and A. M Romanic Cathepsin S expression is up-regulated following balloon angioplasty in the hypercholesterolemic rabbit Cardiovasc Res, June 1, 2004; 62(3): 610 - 620. [Abstract] [Full Text] [PDF]
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 L. Zhang, A. Zalewski, Y. Liu, T. Mazurek, S. Cowan, J. L. Martin, S. M. Hofmann, H. Vlassara, and Y. Shi Diabetes-Induced Oxidative Stress and Low-Grade Inflammation in Porcine Coronary Arteries Circulation, July 29, 2003; 108(4): 472 - 478. [Abstract] [Full Text] [PDF]
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R. C.M Siow, C. M Mallawaarachchi, and P. L Weissberg Migration of adventitial myofibroblasts following vascular balloon injury: insights from in vivo gene transfer to rat carotid arteries Cardiovasc Res, July 1, 2003; 59(1): 212 - 221. [Abstract] [Full Text] [PDF]
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 G. M. Jacobson, H. M. Dourron, J. Liu, O. A. Carretero, D. J. Reddy, T. Andrzejewski, and P. J. Pagano Novel NAD(P)H Oxidase Inhibitor Suppresses Angioplasty-Induced Superoxide and Neointimal Hyperplasia of Rat Carotid Artery Circ. Res., April 4, 2003; 92(6): 637 - 643. [Abstract] [Full Text] [PDF]
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G. Castoldi, C. R. T. di Gioia, F. Pieruzzi, C. D'Orlando, W. M. M. van de Greef, G. Busca, G. Sperti, and A. Stella ANG II increases TIMP-1 expression in rat aortic smooth muscle cells in vivo Am J Physiol Heart Circ Physiol, February 1, 2003; 284(2): H635 - H643. [Abstract] [Full Text] [PDF]
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W.-J. Cai, S. Koltai, E. Kocsis, D. Scholz, S. Kostin, X. Luo, W. Schaper, and J. Schaper Remodeling of the adventitia during coronary arteriogenesis Am J Physiol Heart Circ Physiol, January 1, 2003; 284(1): H31 - H40. [Abstract] [Full Text] [PDF]
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A. Zalewski, Y. Shi, and A. G. Johnson Diverse Origin of Intimal Cells: Smooth Muscle Cells, Myofibroblasts, Fibroblasts, and Beyond? Circ. Res., October 18, 2002; 91(8): 652 - 655. [Full Text] [PDF]
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Z. S. Galis and J. J. Khatri Matrix Metalloproteinases in Vascular Remodeling and Atherogenesis: The Good, the Bad, and the Ugly Circ. Res., February 22, 2002; 90(3): 251 - 262. [Abstract] [Full Text] [PDF]
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S. Sartore, A. Chiavegato, E. Faggin, R. Franch, M. Puato, S. Ausoni, and P. Pauletto Contribution of Adventitial Fibroblasts to Neointima Formation and Vascular Remodeling: From Innocent Bystander to Active Participant Circ. Res., December 7, 2001; 89(12): 1111 - 1121. [Abstract] [Full Text] [PDF]
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P. A. Kingston, S. Sinha, A. David, M. G. Castro, P. R. Lowenstein, and A. M. Heagerty Adenovirus-Mediated Gene Transfer of a Secreted Transforming Growth Factor-{beta} Type II Receptor Inhibits Luminal Loss and Constrictive Remodeling After Coronary Angioplasty and Enhances Adventitial Collagen Deposition Circulation, November 20, 2001; 104(21): 2595 - 2601. [Abstract] [Full Text] [PDF]
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D. Godin, E. Ivan, C. Johnson, R. Magid, and Z. S. Galis Remodeling of Carotid Artery Is Associated With Increased Expression of Matrix Metalloproteinases in Mouse Blood Flow Cessation Model Circulation, December 5, 2000; 102(23): 2861 - 2866. [Abstract] [Full Text] [PDF]
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 M. Gu, J. Lynch, and P. Brecher Nitric Oxide Increases p21Waf1/Cip1 Expression by a cGMP-dependent Pathway That Includes Activation of Extracellular Signal-regulated Kinase and p70S6k J. Biol. Chem., April 6, 2000; 275(15): 11389 - 11396. [Abstract] [Full Text] [PDF]
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G. Li, S.-J. Chen, S. Oparil, Y.-F. Chen, and J. A. Thompson Direct In Vivo Evidence Demonstrating Neointimal Migration of Adventitial Fibroblasts After Balloon Injury of Rat Carotid Arteries Circulation, March 28, 2000; 101(12): 1362 - 1365. [Abstract] [Full Text] [PDF]
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S. Patel, Y. Shi, R. Niculescu, E. H. Chung, J. L. Martin, and A. Zalewski Characteristics of Coronary Smooth Muscle Cells and Adventitial Fibroblasts Circulation, February 8, 2000; 101(5): 524 - 532. [Abstract] [Full Text] [PDF]
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 B. H. Strauss and M. Rabinovitch Adventitial Fibroblasts . Defining a Role in Vessel Wall Remodeling Am. J. Respir. Cell Mol. Biol., January 1, 2000; 22(1): 1 - 3. [Full Text]
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 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]
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