(Circulation. 2001;103:302.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Oral Matrix Metalloproteinase Inhibition and Arterial Remodeling After Balloon Dilation
An Intravascular Ultrasound Study in the Pig
From the Department of Cardiology, University Medical Center, Utrecht (M.J.S., G.P., E.V., P.P.T.d.J., B.J.G.L.d.S., D.P.V.d.K., C.B.); the Interuniversity Cardiology Institute of the Netherlands, Utrecht (M.J.S., G.P., D.P.V.d.K.); and Gaubius Laboratory, TNO-PG, Leiden (J.H.V.), Netherlands.
Correspondence to G. Pasterkamp, MD, PhD, Department of Cardiology, University Medical Center, Heidelberglaan 100, Room G02.523, 3584 CX Utrecht, Netherlands. E-mail g.pasterkamp{at}hli.azu.nl
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Abstract |
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Background—Inhibition of matrix metalloproteinase (MMP) activity after balloon angioplasty by intraperitoneal injection of batimastat reduces late lumen loss by inhibition of constrictive remodeling. In the present study, we investigated whether the oral MMP inhibitor marimastat inhibits constrictive remodeling in favor of neutral or expansive remodeling.
Methods and Results—In
26 pigs, balloon dilation was performed in 101 peripheral arteries.
Pigs were treated with marimastat or served as controls and were
euthanized 42 days after intervention. Intravascular ultrasound was
performed at all time points. Vessel area (VA) loss was assessed by
calculating the change in VA at termination relative to after
intervention. Arteries were divided in 3 categories: expansive
remodeling (VA loss < -5%), neutral (-5% 
VA loss +5%),
and constrictive remodeling (VA loss > +5%). In the marimastat group,
a significant reduction (53%) of late lumen loss was observed that was
fully explained by impaired constrictive remodeling. In the marimastat
group, the prevalence of constrictive remodeling was reduced (38%
versus 75% in the control group) in favor of not only neutral but also
expansive remodeling (21% and 42% versus 4% and 21% in the control
group, respectively, P<0.01).
In contrast to the control group, acute luminal gain in the marimastat
group did not correlate with late VA loss.
Conclusions—Irrespective of the acute luminal gain by balloon dilation, the oral MMP inhibitor marimastat inhibited constrictive arterial remodeling in favor of both neutral and expansive remodeling.
Key Words: metalloproteinases • angioplasty • stenosis • remodeling • ultrasonics
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Introduction |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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For a long time, the 30% to 50% angiographic restenosis rate after balloon angioplasty has been attributed to excessive neointima formation. More recently, both human1 2 and animal3 4 5 6 studies have revealed that constrictive arterial remodeling is the major determinant of restenosis after balloon angioplasty. Arterial remodeling in this context means a structural change in total circumference at the dilated site that ranges from expansive to constrictive remodeling (shrinkage).
Collagen is the major determinant of arterial stiffness and may be considered to be the skeleton of the artery. It has been demonstrated that enhanced collagen breakdown and synthesis are important features in arterial remodeling in the first weeks after balloon angioplasty.7 8 9 Collagen can be degraded only by a family of matrix metalloproteinases (MMPs) that belong to a group of zinc- and calcium-dependent proteases. After balloon angioplasty, a transient increase in MMP activity has been observed.8
Recently, we reported that intraperitoneal injection of batimastat, a nonspecific MMP inhibitor, after balloon angioplasty in atherosclerotic Yucatan minipigs resulted in a significant (50%) reduction in late lumen area loss (LLL) by inhibition of constrictive remodeling.10 Neointima formation was not inhibited.
Little is known about the underlying mechanisms of MMP inhibition after balloon angioplasty. It is unknown whether expansive remodeling is blocked by MMP inhibition as well, resulting in "neutral" remodeling, eg, no change in total circumference. Furthermore, the effect of MMP inhibition on the relationship between acute luminal gain and the 2 determinants of restenosis, arterial remodeling and intimal hyperplasia, is unknown.
In the present study, we monitored the effect of the nonspecific MMP inhibitor marimastat (BB-2516) after balloon dilation in the pig. Marimastat is orally administered, which is a major advantage over batimastat (BB-94), which has to be administered intraperitoneally. It is being applied clinically to prove its role as a tumoristatic agent.11 Marimastat has a collagen-like backbone, which facilitates binding to the active site of the MMP, and a hydroxymate group, which chelates the zinc ion in the active site. All known classes of MMPs in the nanomolar range are inhibited. An unpublished dosimetry study in Landrace pigs in our laboratory revealed that a dose of 10 mg/kg twice a day would give an exposure of 100 to 200 ng/mL plasma, a concentration that has previously been effective in animal models of cancer.
With intravascular ultrasound (IVUS), arterial remodeling and intimal hyperplasia were assessed with and without MMP inhibition and related to short-term luminal gain. Furthermore, we investigated whether MMP inhibition results in enhanced expansive remodeling or in blocking of constrictive remodeling in favor of only neutral remodeling.
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Methods |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Animals
Twenty-six nonatherosclerotic Landrace pigs with an average weight of 20 kg were studied. Balloon dilation was performed in 50 femoral and 51 internal iliac arteries. The animals were euthanized 42 days after intervention. Angiography and IVUS were performed at all time points. The investigation was approved by the Ethical Committee on Animal Experimentation of the Faculty of Medicine, Utrecht University.
Anesthesia
During intervention and euthanization, the animals
were anesthetized with intravenous midazolam 0.3
mg · kg-1 · h-1
and sufentanil 2.5
µg · kg-1 · h-1
and ventilated with a mixture of O2 and air,
1:1, and halothane 1% after a premedication with azaperone 4 mg/kg,
ketamine 10 mg/kg, and thiopental 4 mg/kg.
Intervention
Acetylsalicylic acid was administered to all pigs (80
mg/d), starting with 320 mg 1 day before the intervention. Animals were
heparinized (100 IU/kg), and a continuous infusion of nitroglycerin (20
µg/min) was given to prevent arterial spasm. The arterial tree was
accessed through a right carotid approach. An arterial 8F sheath was
introduced into the descending aorta. An 8F guiding catheter was
advanced to the aortic bifurcation. Through the guiding catheter,
contrast angiography was performed and the IVUS catheter was advanced.
For balloon dilation, a standard peripheral balloon catheter (length 2
to 4 cm, diameter 4 to 6 mm) was advanced to a location that was
identical for all pigs. Pigs underwent balloon dilation of the femoral
and internal iliac arteries at both sides. With a balloon/artery ratio
of 1.2, the balloon was inflated 3 times for 1 minute at a pressure of
8 to 10 atm. After intervention, the right carotid artery was ligated.
For adequate pain relief, buprenorphine hydrochloride 10 µg/kg IM was
injected directly after intervention and for the following 2 days. The
pigs were treated prophylactically with amoxicillin, starting with 250
mg IV at intervention (day 0) and followed by 375 mg LA (long acting)
IM at days 1, 3, and 5.
Angiography and IVUS
Angiography and IVUS were performed before and after
intervention and at follow-up. Radiopaque rulers were used to localize
the treated segments.
Contrast medium (Telebrix, Laboratoire Guerbet) was injected selectively into each artery, preceded by selective injection of nitroglycerin (0.5 mg) to prevent spasm. The fluoroscopy was recorded at a cine rate of 30 images per second with a digital C-arm (Philips). IVUS was performed with a 30-MHz ultrasound transducer (Du-MED) that rotates 16 times per second within a 4.1F catheter. The axial resolution of the system is 0.1 mm. Fluoroscopy was performed during IVUS to document the images relative to an anatomic landmark for adequate matching. The images were recorded on VHS videotape for analysis with a digital videoanalyzer during manual pullback and at regular intervals with the IVUS catheter held still.
Termination
After angiography and IVUS, the animals were killed
by an overdose of pentobarbital.
MMP Inhibition
Marimastat (BB-2516) was supplied by British Biotech
Pharmaceuticals Limited. The animals were randomly divided into a
control group and a marimastat group. The marimastat group was
subdivided into 3 groups with different periods of marimastat
administration (2, 4, and 6 weeks, respectively) for the purpose of
another study. The follow-up of each group, including the control
group, was 6 weeks. The animals started with marimastat, 10 mg/kg twice
a day, 1 day before the intervention. Neither the toxicities described
in previous animal studies (data on file, British Biotech, Inc) nor the
adverse events of marimastat reported in human clinical
trials11 were observed in
the marimastat-treated pigs.
Marimastat Measurements at Tissue Level
Functional marimastat was detected in vascular
extracts as follows. To 10 µL of vascular extract, 1 ng/mL of a
tight-binding MMP inhibitor (BB94) and 45 ng/mL active MMP-9 were added
and incubated at 37°C for 20 minutes. Subsequently, the mixture was
incubated overnight at 4°C on plates coated with anti–MMP-9
antibody (Amersham Pharmacia Biotech RPN 2630 MMP-9 activity
assay kit). After capture, the plate was washed with buffer, and bound
MMP-9 activity was determined according to the kit
instructions.12 The measured
activity originates from the MMP-9/marimastat complex in the vessel
sample and is a representation of the effective marimastat
concentration in the extract. Results were quantified by comparison
with a reference line of various marimastat concentrations (0 to 100
ng/mL) in untreated control vessel extracts. The detection limit of the
method is 
1 ng/mL added marimastat.
Data Analysis
Untreated segments (proximal parts of external iliac
arteries, parts proximal and distal to the dilated segments of the
femoral arteries, parts distal to the dilated segments of the internal
iliac arteries) were used for correction of growth of all
cross-sectional areas as follows: 1-(mean
r2 at death-mean
r2 before intervention)/(mean
r2 at death). The radius of the untreated
segments (r) was determined angiographically.
The IVUS images were analyzed at regular intervals (every
0.5 cm). Anatomic landmarks were used to match the images at different
time points. The balloon-dilated segment was identified by comparison
with the angiogram and confirmed by the existence of acute luminal
gain, which was defined as the difference between postintervention and
preintervention lumen areas. Vessels lacking procedural gain (gain 0
mm) were excluded from further analysis. Within the balloon-dilated
segment, the location with the smallest lumen area at follow-up was
selected for further calculations. LLL was defined as the difference
between lumen area after intervention and at follow-up. Vessel area
(VA) before and after intervention was defined as the inner border of
the echolucent layer within the IVUS image and therefore equals lumen
area before and after intervention. At death, the VA was defined as the
outer border of the echolucent layer and therefore represents lumen,
intimal, and medial area. Loss in VA, being a measure of remodeling,
was calculated by subtracting the VA after intervention and at
follow-up. Intimal hyperplasia was calculated by the difference between
VA and lumen area at follow-up. For each location, the mode of
remodeling (constrictive, neutral, or expansive) was assessed by
calculating the VA at follow-up relative to VA after intervention. The
arteries were divided into 3 categories: expansive remodeling (VA loss
< -5%), neutral remodeling (-5% VA loss +5%), and
constrictive remodeling (VA loss > +5%).
Statistical Analysis
SPSS 8.0 was used for all statistical calculations.
An independent-sample t test
was used for differences between mean values, including maximal and
minimal mean values among the different marimastat groups. A
2 test was used for differences in
distribution of VA changes among groups. A value of
P<0.05 was considered to be
statistically significant. Gain versus LLL and gain versus late VA loss
relationships were calculated with linear
regression.
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Results |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Balloon dilation was performed in 24, 21, and 24 arteries of pigs receiving marimastat for 2, 4, and 6 weeks, respectively (n=6 pigs for each group). In the control group, balloon dilation was performed in 32 arteries of 8 pigs. Nine, 5, and 4 arteries in the marimastat groups and 4 arteries in the control group were excluded because of either lack of gain, extravasation, or excessive thrombus formation (thrombus occupying >30% of lumen area). One pig that was supposed to receive marimastat for 6 weeks (4 arteries) and 1 control pig (4 arteries) died unexpectedly because of ventricular fibrillation and because of a retroperitoneal bleeding due to the intervention, respectively.
In vessel extracts of marimastat-treated animals, 1 to 10 ng/mL functional marimastat was detected.
The
Table
lists the IVUS measurements at different time points. The different
marimastat groups have been pooled, because the duration of
administration did not affect the outcome of marimastat treatment (see
Table, P>0.1 for LLL, VA loss,
and intimal hyperplasia). Acute luminal gain did not differ
significantly between the 2 groups: 4.56±3.03
mm2 in the marimastat group versus
4.92±3.64 mm2 in the control group
(P=0.68).
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Marimastat and LLL, Late VA Loss, and
Intimal Hyperplasia
Figure 1 shows the effect of marimastat on LLL, late VA
loss, and intimal hyperplasia. A 53% reduction in LLL was observed in
the marimastat-treated group compared with the control group. In the
marimastat group, LLL was 2.51±2.61 mm2
versus 5.31±4.78 mm2 in the control group
(P=0.01). Late VA loss was
-0.24±2.85 mm2 in the marimastat group
versus 3.02±4.48 mm2 in the control group
(P<0.01). In the marimastat
group, the reduction in LLL was completely due to the reduction in late
VA loss; no significant difference in intimal hyperplasia was observed
between the 2 groups: 2.74±1.88 mm2 in the
marimastat group versus 2.29±1.54 mm2 in
the control group
(P=0.28).
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VA at Follow-Up Compared With After
Intervention
Figure 2 shows the distribution of the VA loss in both
groups. Compared with the control group, marimastat inhibited
constrictive remodeling in favor of both neutral and expansive
remodeling
(P<0.01).
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Acute Gain and Late VA Loss
Figure 3 shows the relationship between acute gain and late
VA loss in the control group and marimastat group. In the control
group, a significant correlation was observed. In the marimastat group,
however, this correlation was lost.
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Acute Gain and Intimal Hyperplasia
Figure 4 shows the relationship between acute gain and
intimal hyperplasia in the control group and marimastat group. In both
groups, the impact of luminal gain on intimal hyperplasia was small but
significant.
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Marimastat and VA Growth
In untreated segments, the increase in VA did not
differ among groups (P=0.90).
During follow-up, the mean VA growth of untreated segments was 18.66%
(based on 16 pigs) in the marimastat group versus 19.33% in the
control group (7 pigs).
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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The principal findings of the present study were that oral MMP inhibition by marimastat reduced LLL after balloon dilation by blocking constrictive remodeling in favor of both neutral and expansive remodeling. Intimal hyperplasia was not inhibited. In addition, marimastat blocked the constrictive remodeling response irrespective of the acute luminal gain.
Marimastat and Constrictive Remodeling
Constrictive remodeling is the major determinant of
restenosis after balloon
angioplasty.1 2 3 4 5 6
Breakdown and buildup of the extracellular matrix is likely to occur
during this process, which might be comparable to wound contraction.
Geary et al13 showed in the
atherosclerotic monkey that the pattern of matrix and integrin
expression within the injured wall is in many ways analogous to that of
healing wounds. In an in vitro wound contraction model in which
fibroblasts are grown in a collagen matrix, marimastat inhibits lattice
contraction mediated by
fibroblasts,14 a modeling
that may happen when granulation tissue contracts in a healing wound.
These results emphasize the role of MMPs in arterial wall healing after
interventional injury.
The present study supports our earlier observations of the potential therapeutic effect of MMP inhibition by batimastat.10 Marimastat is administered orally, which is a major advantage over batimastat, and has already been clinically applied as a tumoristatic agent.11
Marimastat and Intimal Hyperplasia
Several studies support the role of MMPs in smooth
muscle cell (SMC) migration to the intima. Antibodies to 72-kD type IV
collagenase,15 as well as
batimastat,16 inhibit SMC
migration in vitro. Zempo et
al16 demonstrated
suppression of intimal thickening after arterial injury in the rat by
batimastat. This reduction of intimal area, however, was less at 14
days than at 7 days.
Neointima formation was not inhibited in the present study or in the previous study with batimastat.10 Bendeck et al17 demonstrated a significant reduction in SMC migration in MMP inhibitor–treated rats, resulting in a significant decrease in lesion size early after injury. However, prolonged SMC replication in the MMP inhibitor group resulted in lesion size catching up to controls, resulting in the same intimal area 14 days after balloon injury. It is likely that this "catch-up" phenomenon occurred in the present study, as well as in the study of De Smet et al,10 considering the 42-day follow-up period.
Marimastat and Expansive Remodeling
Marimastat blocked constrictive remodeling not only in
favor of neutral remodeling but also in favor of expansive remodeling.
A possible explanation for this effect of marimastat is that MMPs are
involved in the solubilization of plasma membrane receptors, such as
tumor necrosis factor-
receptors,18 through
proteolytic cleavage of the ligand-binding domain at the cell surface.
This process, called "shedding," is an important mechanism for
regulating cytokine function and receptor signaling and might be
different in constrictive compared with expansive remodeling. Hence,
marimastat may affect each mode of remodeling in a different way.
Furthermore, MMPs may be involved in the maturation of collagen,
because propeptides of collagen are cleaved by
MMPs.19 MMP inhibition might
result in the production of less mature collagen, which might lead to
more mechanical expansion of the vessel wall. However, Spears et
al20 observed that
inhibition of collagen maturation by inhibition of collagen
cross-linking did not induce expansive remodeling, which would
contradict this hypothesis.
The question arises whether MMP inhibition will enhance aneurysm formation. This seems unlikely, because batimastat limits the expansion of experimentally created abdominal aortic aneurysms.21 Furthermore, it has been demonstrated that marimastat inhibits elastin degradation in a model of aneurysm disease.22 MMP inhibition by RS 132908 suppresses aneurysmal dilation in the elastase-induced rodent model of abdominal aortic aneurysm.23
Marimastat and Acute Gain: The Bigger, the
Better
Maximizing the postangioplasty vessel diameter by
deeper, more severe injury might be counterproductive over time because
of augmented neointima formation and constrictive remodeling. In the
rabbit artery, however, Van Erven et
al24 25 found no
difference in intimal hyperplasia within a wide range of arterial
injury. In the present study in the pig, the impact of acute luminal
gain on intimal hyperplasia was relatively small in both groups. In
addition, no relation between acute luminal gain and late VA loss was
observed in the marimastat-treated group, indicating that marimastat
blocked constrictive remodeling irrespective of the acute luminal gain.
Thus, in our animal model, the motto "the bigger, the better" may
apply to balloon dilation in MMP-inhibited arteries. One should
realize, however, that this motto cannot be applied to the increased
complication rate with larger
balloons,26 which may not be
reduced by marimastat treatment.
Limitations of the Study
Constrictive and expansive remodeling after balloon
angioplasty have been reported extensively in different animal models.
The time frame over which constrictive remodeling develops, however,
differs between animals and humans. In peripheral arteries of the
atherosclerotic pig,27
constrictive remodeling starts within days after balloon angioplasty
and seems to be maximal at 6 weeks. In
humans,28 the coronary
artery shows expansive remodeling in the first month, whereas
constrictive remodeling is observed between 1 and 6 months after the
intervention.
In the present study, balloon dilation was performed in internal iliac and femoral arteries. These arteries might respond differently to balloon dilation than do coronary arteries.
The present study was performed in a nonatherosclerotic
model. It is likely that marimastat will exert antirestenotic effects
in an atherosclerotic model as well, because in the atherosclerotic pig
model,10 the precursor of
marimastat, batimastat, reduced LLL also by 50%. One must keep in
mind, however, that in both models, balloon dilation resulted in an
overdilation of the artery, which could result in reduced local shear
force. This is known to induce MMP
activity29 and might also be
influenced by MMP inhibition.
Conclusions
The oral MMP inhibitor marimastat inhibited
constrictive arterial remodeling after balloon dilation in favor of
both neutral and expansive remodeling and irrespective of acute luminal
gain. If these results can be reproduced in human coronary arteries,
MMP inhibition by marimastat may effectively improve the long-term
outcome of coronary balloon
angioplasty.
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Acknowledgments |
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This study was supported by the Dutch Heart Foundation (NHS 99.209). Dr Sierevogel was supported by the Sorbo Foundation. We thank Dr R. Hanemaaijer, Gaubius Laboratory, TNO-PG, Leiden, Netherlands, for his contribution in the marimastat measurements at the tissue level.
Received May 25, 2000; revision received July 26, 2000; accepted July 28, 2000.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Mintz GS, Popma JJ, Pichard AD, et al. Arterial remodeling after coronary angioplasty: a serial intravascular ultrasound study. Circulation. 1996;94:35–43.
2. Di Mario C, Gil R, Camenzind E, et al. Quantitative assessment with intracoronary ultrasound of the mechanisms of restenosis after percutaneous transluminal coronary angioplasty and directional atherectomy. Am J Cardiol. 1995;75:772–777.[Medline] [Order article via Infotrieve]
3.
Post MJ, Borst C,
Kuntz RE. The relative importance of arterial remodeling compared to
intimal hyperplasia in lumen renarrowing following balloon angioplasty:
a study in the normal rabbit and the hypercholesterolemic Yucatan
micropig. Circulation. 1994;89:2816–2821.
4.
Post MJ, De Smet B,
van der Helm Y, et al. Arterial remodeling after balloon angioplasty or
stenting in an atherosclerotic experimental model.
Circulation. 1997;96:996–1003.
5.
Kakuta T, Currier
JW, Haudenschild CC, et al. Differences in compensatory vessel
enlargement, not intimal formation, account for restenosis after
angioplasty in the hypercholesterolemic rabbit model.
Circulation. 1994;89:2809–2815.
6.
Lafont A, Guzman
LA, Whitlow PL, et al. Restenosis after experimental angioplasty:
intimal, medial, and adventitial changes associated with constrictive
remodeling. Circ Res. 1995;76:996–1002.
7.
Strauss BH,
Chisholm RJ, Keeley FW, et al. Extracellular matrix remodeling after
balloon angioplasty injury in a rabbit model of restenosis.
Circ Res. 1994;75:650–658.
8.
Strauss BH,
Robinson R, Batchelor WB, et al. In vivo collagen turnover following
experimental balloon angioplasty injury and the role of matrix
metalloproteinases. Circ Res. 1996;79:541–550.
9.
Coats WD Jr,
Wittaker P, Cheung DT, et al. Collagen content is significantly lower
in restenotic versus nonrestenotic vessels after balloon angioplasty in
the atherosclerotic rabbit model.
Circulation. 1997;95:1293–1300.
10.
De Smet BJGL, De
Kleijn DPV, Hanemaaijer H, et al. Metalloproteinase inhibition reduces
constrictive arterial remodeling following balloon angioplasty: a study
in the atherosclerotic Yucatan micropig.
Circulation. 2000;101:2962–2967.
11. Nemunaitis J, Poole C, Primrose J, et al. Combined analysis of studies of the effects of the matrix metalloproteinase inhibitor marimastat on serum tumor markers in advanced cancer: selection of a biologically active and tolerable dose for longer-term studies. Clin Cancer Res. 1998;4:1101–1109.[Abstract]
12. Hanemaaijer R, Visser H, Konttinen YT, et al. A novel and simple immunocapture assay for determination of gelatinase B (MMP-9) activities in biological fluids: saliva from patients with Sjogren’s syndrome contain increased latent and active gelatinase B levels. Matrix Biol. 1998;17:657–665.[Medline] [Order article via Infotrieve]
13. Geary R, Nikkari S, Wagner W, et al. Wound healing: a paradigm for lumen narrowing after arterial reconstruction. J Vasc Surg.. 1998;27:96–108.[Medline] [Order article via Infotrieve]
14. Scott K, Wood E, Karran E. A matrix metalloproteinase inhibitor which prevents fibroblast-mediated collagen lattice contraction. FEBS Lett. 1998;441:137–140.[Medline] [Order article via Infotrieve]
15.
Pauly RR,
Passaniti A, Bilato C, et al. 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.
16.
Zempo N, Koyama
N, Kenagy RD, et al. Regulation of vascular smooth muscle cell
migration and proliferation in vitro and in injured rat arteries by a
synthetic matrix metalloproteinase inhibitor.
Arterioscler Thromb Vasc Biol. 1996;16:28–33.
17.
Bendeck MP, Irvin
C, Reidy MA. Inhibition of matrix metalloproteinase activity inhibits
smooth muscle cell migration but not neointimal thickening after
arterial injury. Circ Res. 1996;78:38–43.
18.
Lombard MA,
Wallace TL, Kubicek MF, et al. Synthetic matrix metalloproteinase
inhibitors and tissue inhibitor of metalloproteinase (TIMP)-2, but not
TIMP-1, inhibit shedding of tumor necrosis factor- receptors in a
human colon adenocarcinoma (colo 205) cell line.
Cancer Res.. 1998;58:4001–4007.
19. Prockop DJ, Sieron AL, Li SW. Procollagen N-proteinase and procollagen C-proteinase: two unusual metalloproteinases that are essential for procollagen processing probably have important roles in development and cell signaling. Matrix Biol. 1998;16:399–408.[Medline] [Order article via Infotrieve]
20. Spears JR, Zhan H, Khurana S, et al. Modulation by ß-aminopropiononitrile of vessel luminal narrowing and structural abnormalities in arterial wall collagen in a rabbit model of conventional balloon angioplasty versus laser balloon angioplasty. J Clin Invest. 1984;93:1543–1553.
21. Bigatel DA, Elmore JR, Carey DJ, et al. The matrix metalloproteinase inhibitor BB-94 limits expansion of experimental abdominal aortic aneurysms. J Vasc Surg. 1999;29:130–139.[Medline] [Order article via Infotrieve]
22. Treharne GD, Boyle JR, Goodall S, et al. Marimastat inhibits elastin degradation and matrix metalloproteinase 2 activity in a model of aneurysm disease. Br J Surg. 1999;86:1053–1058.[Medline] [Order article via Infotrieve]
23. Moore M, Shixiong L, Curci JA, et al. Suppression of experimental abdominal aortic aneurysms by systemic treatment with a hydroxamate-based matrix metalloproteinase inhibitor (RS 132908). J Vasc Surg. 1999;29:522–532.[Medline] [Order article via Infotrieve]
24. Van Erven L, Velema E, Bos AN, et al. Thrombogenicity and intimal hyperplasia after conventional and thermal balloon dilation in normal rabbit iliac arteries. J Vasc Res.1992;29:426–434.
25. Van Erven L, Post MJ, Velema E, et al. In the normal rabbit femoral artery increasing arterial wall injury does not lead to increased intimal hyperplasia. J Vasc Res. 1994;31:153–162.[Medline] [Order article via Infotrieve]
26.
Roubin GS,
Douglas JS Jr, King SB III, et al. Influence of balloon size on initial
success, acute complications, and restenosis after percutaneous
transluminal coronary angioplasty: a prospective randomized study.
Circulation. 1988;78:557–565.
27.
De Smet BJ, van
der Zande J, van der Helm YJ, et al. The atherosclerotic Yucatan animal
model to study the arterial response after balloon angioplasty: the
natural history of remodeling. Cardiovasc
Res. 1998;39:224–232.
28.
Kimura T,
Kaburagi S, Tamura T, et al. Remodeling of human coronary arteries
undergoing coronary angioplasty or atherectomy.
Circulation. 1997;96:475–483.
29.
Bassiouny HS,
Song RH, Hong XF, et al. Flow regulation of 72-kD collagenase IV
(MMP-2) after experimental arterial injury.
Circulation. 1998;98:157–163.
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 G. Pasterkamp, Z. S. Galis, and D. P.V. de Kleijn Expansive Arterial Remodeling: Location, Location, Location Arterioscler Thromb Vasc Biol, April 1, 2004; 24(4): 650 - 657. [Abstract] [Full Text] [PDF]
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 S. C.G. Hollestelle, M. R. de Vries, J. K. van Keulen, A. H. Schoneveld, A. Vink, C. F. Strijder, B. J. van Middelaar, G. Pasterkamp, P. H.A. Quax, and D. P.V. de Kleijn Toll-Like Receptor 4 Is Involved in Outward Arterial Remodeling Circulation, January 27, 2004; 109(3): 393 - 398. [Abstract] [Full Text] [PDF]
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J. P.G Sluijter, M. B Smeets, E. Velema, G. Pasterkamp, and D. P.V de Kleijn Increased collagen turnover is only partly associated with collagen fiber deposition in the arterial response to injury Cardiovasc Res, January 1, 2004; 61(1): 186 - 195. [Abstract] [Full Text] [PDF]
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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]
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 Z. S. Galis, C. Johnson, D. Godin, R. Magid, J. M. Shipley, R. M. Senior, and E. Ivan Targeted Disruption of the Matrix Metalloproteinase-9 Gene Impairs Smooth Muscle Cell Migration and Geometrical Arterial Remodeling Circ. Res., November 1, 2002; 91(9): 852 - 859. [Abstract] [Full Text] [PDF]
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M. J Sierevogel, E. Velema, F. J van der Meer, M. O. Nijhuis, M. Smeets, D. P.V de Kleijn, C. Borst, and G. Pasterkamp Matrix metalloproteinase inhibition reduces adventitial thickening and collagen accumulation following balloon dilation Cardiovasc Res, September 1, 2002; 55(4): 864 - 869. [Abstract] [Full Text] [PDF]
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G. Pasterkamp, M. J. Sierevogel, D. P.V. de Kleijn, B. H. Strauss, R. L. Geary, and G. S. Cherr MMP Inhibition and Lumen Loss After Balloon Angioplasty or Stenting * In Response Arterioscler Thromb Vasc Biol, July 1, 2002; 22(7): 1241 - 1241. [Full Text] [PDF]
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 C. Li, W. J. Cantor, N. Nili, R. Robinson, L. Fenkell, Y. L. e Tran, H. A. Whittingham, W. Tsui, A. N. Cheema, J. D. Sparkes, et al. Arterial repair after stenting and the effects of gm6001, a matrix metalloproteinase inhibitor J. Am. Coll. Cardiol., June 5, 2002; 39(11): 1852 - 1858. [Abstract] [Full Text] [PDF]
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 I. Loftus and M. Thompson The role of matrix metalloproteinases in vascular disease Vascular Medicine, May 1, 2002; 7(2): 117 - 133. [Abstract] [PDF]
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E. E.J.M. Creemers, J. P.M. Cleutjens, J. F.M. Smits, and M. J.A.P. Daemen Matrix Metalloproteinase Inhibition After Myocardial Infarction: A New Approach to Prevent Heart Failure? Circ. Res., August 3, 2001; 89(3): 201 - 210. [Abstract] [Full Text] [PDF]
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 M. J. Sierevogel, E. Velema, P. P. de Jaegere, D. P. de Kleijn, C. Borst, and G. Pasterkamp Minimal Duration of Oral Matrix Metalloproteinase Inhibition to Prevent Constrictive Arterial Remodeling after Balloon Dilation in the Pig Radiology, February 1, 2002; 222(2): 468 - 473. [Abstract] [Full Text] [PDF]
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