© 1996 American Heart Association, Inc.
Articles |
Nitric Oxide Reversibly Inhibits the Migration of Cultured Vascular Smooth Muscle Cells
From the Departments of Physiology (R.S., R.C.W.), Surgery (R.S., E.G.M., J.C.S.), and Pathology (D.G.), University of Michigan Medical School, Ann Arbor.
Correspondence to Rajabrata Sarkar, MD, PhD, Department of Physiology, University of Michigan Medical School, 7813 MS II, 1301 Catherine Rd, Ann Arbor, MI 48109-0622. E-mail rsarkar@ucla.edu.
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Abstract |
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 Top Abstract IntroductionMaterials and Methods Results Discussion References |
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Abstract Augmentation of nitric oxide (NO) production in vivo decreases lesions in a variety of models of arterial injury, and inhibition of NO synthase exacerbates experimental intimal lesions. Both vascular smooth muscle cell (VSMC) proliferation and migration contribute to lesion formation. Although NO inhibits VSMC proliferation, its effects on VSMC migration are unknown. To test the hypothesis that NO inhibits VSMC migration independent of inhibition of proliferation, we examined migration of rat aortic VSMCs after wounding of a confluent culture in the presence of chemical donors of NO. Hydroxyurea was used to eliminate any confounding effect of NO on proliferation. Three NO donors, diethylamine NONOate, spermine NONOate, and S-nitrosoglutathione, exhibited concentration-dependent inhibition of both number of migrating VSMCs and maximal distance migrated. Inhibition of migration was also seen with 8-Br-cGMP, suggesting that activation of guanylate cyclase may play a role in mediating the antimigratory effects of NO. Migration resumed after removal of NO donors, as evidenced by an increase in distance migrated. Measurement of VSMC protein synthesis and mitochondrial respiration indicated that inhibition of migration by NO donors was not due to metabolic cytostasis. These findings indicate that NO reversibly inhibits VSMC migration independent of proliferation or cytotoxicity, a novel mechanism by which both endogenous and pharmacological NO may alter vascular pathology.
Key Words: atherosclerosis • cell migration • nitric oxide
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Introduction |
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TopAbstractIntroductionMaterials and Methods Results Discussion References |
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Nitric oxide modulates several physiological processes in the vasculature, including vascular tone, platelet aggregation, and leukocyte adhesion to the endothelium. Augmentation of NO production under pathological conditions results in diminished neointimal lesion formation in several experimental models. Dietary supplementation with L-arginine, the precursor for NO, improves endothelium-dependent relaxation and diminishes intimal lesions after balloon angioplasty.1 2 Similar effects are seen after balloon catheter injury with infusion of a pharmacological NO donor3 or gene transfer of NO synthase to the injured artery.4 The benefit of increasing NO on intimal lesions has also been shown in other clinically relevant models of vessel injury, including cholesterol-induced atherogenesis5 and vein grafting into the arterial circulation.6 A role for endogenous NO in limiting neointimal hyperplasia is illustrated by in vivo studies demonstrating that treatment with inhibitors of NO synthase after balloon injury2 or cholesterol feeding7 increases neointimal hyperplasia.
Despite evidence that NO inhibits neointimal hyperplasia in several different experimental models, the mechanisms involved in this inhibition by NO are unclear. Formation of intimal lesions involves VSMC proliferation, migration of VSMCs through the internal elastic lamina into the intima, and deposition of extracellular matrix. NO donors have been shown to inhibit proliferation of cultured VSMCs,8 9 10 11 and decreased VSMC proliferation has been noted in vivo after NO augmentation by gene transfer.4 The effects of NO on other processes involved in neointima formation are less clear. Exogenous NO inhibits the production of collagen and total protein in vascular VSMCs,12 and inhibition of extracellular matrix deposition may contribute to the in vivo effects of NO on neointima formation. Inhibition of VSMC migration may be another mechanism by which NO inhibits neointima formation under physiological and pathological conditions. NO has divergent effects on cell migration that are cell-type specific. NO synthase inhibitors decrease migration of human neutrophils,13 and this effect appears to be mediated by decreasing levels of the second messenger cGMP. NO also has promigratory effects on capillary endothelial cells,14 which appear to be cGMP mediated. In contrast, exogenous NO inhibits migration of monocytes by increasing cGMP levels.15
The purpose of our study was to test the hypothesis that NO inhibits the migration of VSMCs in vitro and to examine the mechanisms involved in such inhibition. We used the well-characterized wounding model of in vitro cell migration16 17 to examine the effects of chemically derived NO on migration of cultured VSMCs. Our data demonstrate that multiple donors of NO inhibit the migration of VSMCs in a concentration-dependent, reversible, and noncytotoxic fashion. These findings delineate an additional mechanism that may explain the inhibitory effects of NO on neointimal hyperplasia in vivo.
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Materials and Methods |
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TopAbstractIntroductionMaterials and Methods Results Discussion References |
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DMEM, trypsin-EDTA, glutamine, and penicillin/streptomycin were from GIBCO Labs. Fetal bovine serum was purchased from Hyclone. [3H]Thymidine and [3H]leucine were obtained from Amersham. GSNO was from Alexis Biochemicals. DEA NO and SP NO were purchased from Cayman Chemical. All other reagents were supplied by Sigma Chemical Co.
VSMC Culture and Migration Assay
Rat aortic VSMCs were
derived from the thoracic aortas of adult
male Sprague-Dawley rats by using standard enzymatic
dissociation techniques and were characterized as previously
described.18 Cells were plated and grown in DMEM
supplemented with 10% (vol/vol) fetal bovine serum, 1 mmol/L
glutamine, and penicillin/streptomycin. VSMC migration was assessed
with a razor blade wounding injury of confluent cultured
cells.16 17 Migration from a wounded confluent
culture is
dependent on the density of the culture, and thus in all experiments,
cells (passages 4 through 10) were plated into 100-mm dishes at a
constant density of 7000 cells/cm2 and grown for 9 days
before use. Medium was changed every other day for 9 days and then
replaced with medium containing 5 mmol/L hydroxyurea. Hydroxyurea was
added to eliminate any confounding effects of NO on cell proliferation,
as both NO and exogenous cGMP inhibit proliferation of cultured
VSMCs,8 and proliferation contributes to the number of
migrating cells in scratch injury models of cell
migration.16 Preliminary experiments showed that 24-hour
treatment with 5 mmol/L hydroxyurea resulted in complete inhibition of
cell proliferation (thymidine uptake <1% of untreated control cells)
similar to previous studies, which have also shown that 5 mmol/L
hydroxyurea does not alter VSMC migration compared with irradiated
cells.16 After 24 hours of hydroxyurea treatment, the
cultures were scraped with a single-edged razor blade. Care was
taken to ensure that a discernible scratch resulted that could be found
upon later examination. Cells were washed twice with PBS and placed in
medium containing hydroxyurea and experimental agents. Whenever
experimental agents were dissolved in buffers other than medium,
control cells were treated with appropriate concentrations of buffer
alone. Medium containing NO donors was changed every 12 hours (24 hours
for 8-Br-cGMP), and 48 hours after the initial wounding, cells were
washed twice with PBS, fixed with absolute ethanol, and stained with
toluidine blue. Three microscopic fields (2-mm diameter) were evaluated
for each wounding injury. The number of cells migrating across the
wound edge and the maximum distance migrated (wound edge to nucleus of
farthest cell) were determined in each field and averaged for each
injury (see Fig 1
). Reversal experiments were performed
in which VSMCs were treated with NO donors for 48 hours and then
allowed to migrate for an additional 48 hours in medium without NO
donors. The purpose of these experiments was to determine whether VSMCs
inhibited from migrating by NO for 48 hours were still capable of
migration or whether irreversible changes had occurred. After 48-hour
exposure to 0.6 mmol/L DEA NO or SP NO, VSMCs were washed twice with
PBS and placed in fresh medium containing hydroxyurea without NO donors
for an additional 48 hours before assessment of migration, as described
above. Migration of the reversal VSMCs was compared with identically
treated VSMCs exposed to NO donors for 48 hours to evaluate whether
migration resumed in the second 48-hour period without NO donors.
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P<.05 vs SP NO.
NO Donors
The nucleophilic adducts of NO, SP NO and DEA NO,
release free
NO in a pH-dependent fashion, with release initiated on mixing of stock
solution (pH >8.5) with culture medium (pH 7.4).19 Stock
solutions (100 mmol/L) were prepared in phosphate buffer (50 mmol/L
Na2HPO4, pH 8.5) and stored for no more
than 3 days at -70°C. Dissociation of nucleophilic adducts of
NO follows first-order kinetics, with complete dissociation
occurring within 1 hour, and thus media containing DEA NO or SP NO were
changed every 12 hours during migration studies. The antimigratory
properties of diethylamine, the non–NO-releasing analogue of DEA NO,
were evaluated to confirm that the effects of DEA NO were due to NO
release. In other experiments, VSMCs were treated with SP NO that had
been preincubated with medium for 12 hours at 37°C, which causes both
complete dissociation of NO from the nucleophilic complex (SP NO
half-life=47 minutes at pH 7.4) and conversion of the labile NO to
its biologically inactive metabolite nitrite. The nitrosothiol NO donor
GSNO20 was dissolved in PBS (50 mmol/L) immediately before
application to cells. A stable cell-permeable analogue of cGMP,
8-Br-cGMP, was dissolved in medium and applied every 24 hours after
wounding of cultures.
Cytotoxicity Assays
After 48-hour treatment with 1 mmol/L DEA
NO or SP NO, cells
were washed twice with PBS and exposed to 0.1% trypan blue for 5
minutes and the percentage of trypan blue–positive cells
determined. For evaluation of mitochondrial respiration in VSMCs
treated with NO donors, the MTT reduction technique21 was
used. MTT serves as a substrate for mitochondrial dehydrogenases, which
reduce MTT to insoluble formazan. VSMCs were pretreated with
hydroxyurea (5 mmol/L) and treated with DEA NO (0.6 mmol/L), SP NO (0.6
mmol/L), or 8-Br-cGMP (1 mmol/L) in identical fashion to cells in
migration assays. Control cells were exposed to hydroxyurea alone to
match control cells in migration assays. Four hours after the last
medium change (total exposure to NO donors was 40 hours), MTT (0.3
mg/mL) was added for 2 additional hours. Cells were washed with PBS and
then solubilized in isopropanol containing 0.1 mol/L HCl and 1% Triton
X-100. The solubilized formazan was measured by determining
A570, and background (A690) was
subtracted for each sample. For measurement of VSMC protein synthesis,
cells were treated with NO donors or hydroxyurea alone, as described
for mitochondrial respiration assays, and then
[3H]leucine (5 µCi/mL) was added for 1 hour,
beginning
4 hours after the last addition of NO donors. Incorporation of
radioleucine into protein was determined by a standard
technique12 of fixing cells with cold methanol after 1
hour, precipitating protein with three washes with cold trichloroacetic
acid (10%), and solubilizing precipitates with 0.3 mol/L sodium
hydroxide before scintillation counting. Incorporation of radioleucine
measured by this technique was inhibited by cycloheximide in a
concentration-dependent fashion (EC50=0.03 µg/mL),
confirming that incorporation reflected protein synthesis.
Data Analysis and Statistics
Three 2-mm fields were evaluated
for each wounding, and the
number of migrating cells and the farthest distance migrated were
determined. These three values were averaged to give a mean for each
wounding. These mean values (n=8 to 22 from 2 to 5 separate
experiments) were each then normalized to appropriately treated control
plates for each experiment to allow comparison between experiments and
then averaged to give the data shown (mean±SEM). Differences between
groups were analyzed with one-way analysis of
variance with Bonferroni correction for repeated comparisons where
appropriate. If analysis of variance demonstrated significant
differences between groups, then individual differences were
analyzed with a two-tailed unpaired t test.
Differences were considered significant when P<.05.
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Results |
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TopAbstractIntroductionMaterials and Methods Results Discussion References |
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Migration of VSMCs for 48 hours in control cultures resulted in 68±3 cells crossing the wound edge, with a maximal distance migrated of 428±14 µm (mean±SEM, n=53 to 56 woundings). The addition of the NO donors SP NO, DEA NO, and GSNO caused similar concentration-dependent inhibition of both the number of VSMCs migrating across the wound edge and the farthest distance migrated (Fig 2A
through 2C). Inhibition of migration was
statistically significant (P<.05) beginning at a
concentration of 0.1 mmol/L for all three NO donors. The maximal
inhibition achieved with the nucleophilic adducts of NO (SP NO and DEA
NO) was greater (
80%) than that obtained with the nitrosothiol GSNO
(50%) at similar concentrations (1 mmol/L).
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The non–NO-releasing analogue of DEA NO, diethylamine (1 mmol/L), had
no significant effect on either number of VSMCs migrating or distance
migrated, whereas DEA NO (1 mmol/L) inhibited both
parameters of migration (Fig 3). Treatment
of VSMCs with fresh SP NO (0.6 mmol/L) resulted in inhibition of
60% of VSMC migration (Figs 2B
and 3B) over
48 hours, whereas VSMCs
treated with SP NO (0.6 mmol/L) that had been preincubated at 37°C
for 12 hours resulted in significantly less inhibition of migration
(Fig 3). Placement of VSMCs treated with 0.6 mmol/L DEA NO or
SP NO for
48 hours in fresh medium for an additional 48 hours resulted in an
almost twofold increase in distance of VSMC migration relative to
migration during the NO treatment period (Fig 1A), although the
number
of VSMCs migrating did not significantly increase during the 48-hour
recovery period (Fig 1A). Increasing concentrations of
8-Br-cGMP
showed progressive inhibition of both the number of migrating VSMCs and
distance of migration (Fig 4); these differences,
however, reached statistical significance only at the maximal
concentration tested (1 mmol/L).
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Trypan blue exclusion was used to evaluate whether treatment with NO
donors caused increased cell death. Exposure of VSMCs to 0.1% trypan
blue after 48-hour treatment with DEA NO and SP NO (1 mmol/L)
consistently resulted in exclusion of trypan blue by >99% of
cells, which was similar to control VSMCs. Measurement of mitochondrial
respiration demonstrated (Fig 5) that there was no
inhibition of VSMC mitochondrial respiration by NO donors at
concentrations (0.6 mmol/L) that significantly inhibited migration (Fig
2A and 2B). In protein synthesis experiments,
control VSMCs
incorporated 0.253±0.009 cpm/cell (mean±SEM, n=6) of
radioleucine in
the 1-hour incubation period. The rate of protein synthesis was
decreased in cells treated with SP NO by 28% but not significantly
altered in cells exposed to DEA NO (Fig 5). Treatment with
8-Br-cGMP increased both protein synthesis and mitochondrial
respiration relative to control VSMCs (Fig 5).
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Discussion |
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TopAbstractIntroductionMaterials and Methods Results Discussion References |
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Our findings demonstrate that exogenous, chemically derived NO inhibits migration of VSMCs independent of effects on proliferation. This inhibition was not due to suppression of VSMC proliferation, as all studies were done in the presence of hydroxyurea block, a technique designed to detect antimigratory effects of agents such as heparin16 that also inhibit VSMC proliferation. Three experimental findings strongly support the concept that the inhibitory effects noted in our studies were due to NO: (1) Inhibition of VSMC migration occurred at similar concentrations with three structurally different NO donors (Fig 2A
through 2C),
including
donors that release NO via different mechanisms, ie, nucleophilic NO
adducts (DEA NO and SP NO) and a nitrosothiol (GSNO). (2) Inhibition of
VSMC migration by SP NO was abolished by preincubating SP NO with
medium (Fig 3), demonstrating lability of the inhibitory
factor, consistent with the biology of NO. (3) Inhibition of
migration by DEA NO was not mimicked by its inactive analogue
diethylamine, which lacks a nucleophilic complex with NO (Fig
3). As
previously described by other investigators,8 12 the
"stale SP NO" experiment (Fig 3) also excludes the
possibility
that the effect of SP NO is not a direct effect on VSMCs but rather a
degradation by NO of promigratory factors present in the serum or
medium. Significant inhibition of VSMC migration in our studies by all three NO donors occurred at concentrations (0.1 to 1 mmol/L) similar to those that inhibit proliferation8 9 10 11 and collagen synthesis of VSMCs in vitro.12 Furthermore, these concentrations of NO donors are the same as those that inhibit the in vitro migration of monocytes15 and augment neutrophil migration.13 A concern regarding these concentrations of NO donors is that they are several orders of magnitude greater than concentrations required to affect vasoreactivity and platelet aggregation in vitro.20 The development of neointimal hyperplasia, involving VSMC proliferation, migration, and matrix deposition, and the inhibition of these processes by NO in vivo occur over weeks. Higher concentrations of exogenous NO are required to demonstrate inhibition of these cellular functions in short-term in vitro experiments with cultured VSMCs8 9 10 11 12 as well as other cell types.13 15
Perhaps most importantly, VSMC migration resumed after removal of NO
from the culture medium, demonstrating that the inhibition is
reversible. Removal of NO donors in concentrations higher than those
used in this study resulted in reversal of inhibition of VSMC collagen
and protein synthesis,12 confirming that
inhibitory effects of exogenous NO on VSMCs are not simply
due to cytotoxicity. In the reversal experiments (Fig 1),
removal of NO
donors resulted in a subsequent increase in distance migrated but not
number of migrating cells. This finding suggests that prolonged
treatment of VSMCs with NO donors affects cells that have begun
migrating different from cells that did not initially migrate while
treated with NO donors. An alternative explanation for this effect,
which was seen with both DEA NO and SP NO, is that
heterogeneity exists within the population of cultured
VSMCs with respect to sensitivity to NO. Our studies also did not
examine whether the inhibitory effects of NO donors on VSMC
migration are lost after 48 hours. Further studies will be needed to
address these issues.
NO activates smooth muscle guanylate cyclase, and
treatment of cultured rat VSMCs with NO donors causes rapid increases
in intracellular cGMP.11 Inhibition of VSMC migration by
8-Br-cGMP (Fig 4) indicates that cGMP elevation by NO may play
a
role in the inhibition of VSMC migration noted with NO donors (Fig
2A
through 2C), as has been shown for NO modulation of migration of other
cell types.13 15 We did not use agents such as
methylene
blue to block activation of guanylate cyclase, as methylene
blue releases oxygen radicals that bind and inactivate
nitric oxide extracellularly,22 a confounding factor that
does not allow these agents to be used to determine the role of
guanylate cyclase in mediating the biological activity of
exogenous NO. The maximal inhibition of migration obtained with cGMP
(20% to 30%) was less than that obtained with NO donors (80% to
90%). A similar discrepancy between the efficacies of exogenous NO and
exogenous 8-Br-cGMP is seen in inhibition of VSMC
proliferation8 10 and may indicate that other signal
transduction pathways are involved in mediating these
inhibitory effects of NO on VSMCs.
We examined the effects of two NO donors on mitochondrial
respiration and protein synthesis because NO can inactivate
iron-containing enzymes of the mitochondrial electron transport
chain as well as the enzyme aconitase in the citric acid cycle, leading
to energy depletion and decreased protein synthesis.23
Because cell motility has been shown to require protein
synthesis,24 we examined the possibility that the
inhibition of VSMC migration seen with NO donors was associated with
significant inhibition of protein synthesis or mitochondrial
respiration. Although SP NO decreased protein synthesis by 28% (Fig
5), DEA NO had no effect. Since both DEA NO and SP NO have
similar
potencies in inhibiting VSMC migration (Fig 2A and
2B), the differences
in protein synthesis suggest that this is an effect that is specific
for SP NO and thus is not the mechanism by which exogenous NO inhibits
VSMC migration.
No inhibition of mitochondrial respiration was noted with either NO
donor (Fig 5), and we found that 8-Br-cGMP (1 mmol/L), which
inhibited VSMC migration (Fig 4), increased both protein
synthesis and
mitochondrial respiration relative to control cells (Fig 5).
Although
we cannot define the mechanism by which 8-Br-cGMP increases these
two cellular functions, the opposite effects of exogenous cGMP on VSMC
migration versus respiration and protein synthesis further demonstrate
that the inhibition of migration by NO and cGMP is not due to
inhibition of global cellular function.
Our studies illustrate that NO inhibits chemokinesis, or random migration of VSMCs. Further studies are needed to determine whether NO inhibits chemotaxis, or directed migration of VSMCs. The relevance of inhibition of chemokinesis of VSMCs in the wounded culture model is illustrated by the use of this model to demonstrate that heparin inhibits VSMC migration independent of proliferation in vitro.16 These findings were reflected in vivo, where heparin inhibits the migration of nondividing VSMCs to the intima after arterial injury.25
NO donors have been shown to inhibit VSMC proliferation in vitro8 11 as well as VSMC collagen production in vitro.12 These previous studies illustrate two possible mechanisms by which augmentation of NO production in vivo inhibits intimal lesion formation in different vascular injury models.1 2 5 6 Our observations delineate a third potential mechanism to explain how NO limits development of neointimal hyperplasia after vessel injury, namely, by inhibition of VSMC migration from the medium to the developing lesion in the intima.
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Selected Abbreviations and Acronyms |
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Acknowledgments |
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Dr Sarkar was supported by a National Research Service Award (F32 HL-08677). Eric Meinberg was a Student Research Fellow of the American Heart Association of Michigan. Additional support was provided by National Institutes of Health grants HL-18575 (to Dr Webb) and HL-02816 (to Dr Stanley) and by the Conrad Jobst Research Laboratories.
Received June 5, 1995; accepted October 27, 1995.
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References |
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TopAbstractIntroductionMaterials and Methods Results Discussion References |
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1. Tarry WC, Makhoul RG. L-Arginine improves endothelium-dependent vasorelaxation and reduces intimal hyperplasia after balloon angioplasty. Arterioscler Thromb. 1994;14:938-943.
2. McNamara DB, Bedi B, Aurora H, Tena L, Ignarro LJ, Kadowitz PJ, Akers DL. L-Arginine inhibits balloon catheter-induced intimal hyperplasia. Biochem Biophys Res Commun. 1993;193:291-296. [Medline] [Order article via Infotrieve]
3.
Guo J, Milhoan KA, Tuan RS, Lefer AM.
Beneficial effect of SPM-5185, a cysteine-containing nitric oxide
donor, in rat carotid artery intimal injury.
Circ Res. 1994;75:77-84.
4.
van der Leyen HE, Gibbons GH, Morishita R, Lewis NP,
Zwang L, Nakajima M, Kaneda Y, Cooke JP, Dzau VJ. Gene therapy
inhibiting neointimal hyperplasia: in
vivo transfer of endothelial nitric oxide synthase
gene. Proc Natl Acad Sci U S A. 1995;92:1137-1141.
5. Cooke JP, Singer AH, Tsao P, Zera P, Rowan RA, Billingham ME. Anti-atherogenic effects of L-arginine in the hypercholesterolemic rabbit. J Clin Invest. 1992;90:1168-1172.
6. Davies MG, Kim JH, Dalen H, Makhoul RG, Svendsen E, Hagen PO. Reduction of experimental vein graft intimal hyperplasia and preservation of nitric oxide–mediated relaxation by the nitric oxide precursor L-arginine. Surgery. 1994;116:557-568. [Medline] [Order article via Infotrieve]
7.
Cayatte AJ, Palacino JJ, Horten K, Cohen RA.
Chronic inhibition of nitric oxide production accelerates
neointima formation and impairs endothelial
function in hypercholesterolemic rabbits.
Arterioscler Thromb. 1994;14:753-759.
8. Garg UC, Hassid A. Nitric oxide–generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J Clin Invest. 1989;83:1774-1777.
9.
Cornwell TL, Arnold E, Boerth NJ, Lincoln TM.
Inhibition of smooth muscle cell growth by nitric oxide and activation
of cAMP-dependent protein kinase by cGMP. Am J
Physiol. 1994;267:C1405-C1413.
10.
Dubey RK. Vasodilator-derived nitric oxide
inhibits fetal calf serum- and angiotensin-II–induced
growth of renal arteriolar smooth muscle cells. J
Pharmacol Exp Ther. 1994;269:402-408.
11. Kariya K, Kawahara Y, Araki S, Fukuzaki H, Takai Y. Antiproliferative action of cyclic GMP–elevating vasodilators in cultured rabbit aortic smooth muscle cells. Atherosclerosis. 1989;80:143-147. [Medline] [Order article via Infotrieve]
12.
Kolpakov V, Gordon D, Kulik TJ. Nitric
oxide–generating compounds inhibit total protein and collagen
synthesis in cultured vascular smooth muscle cells.
Circ Res. 1995;76:305-309.
13. Belensky SN, Robbins RA, Rennard SI, Gossman GL, Nelson KJ, Rubinstein I. Inhibitors of nitric oxide synthase attenuate human neutrophil chemotaxis in vitro. J Lab Clin Med. 1993;122:388-394. [Medline] [Order article via Infotrieve]
14. Ziche M, Morbidelli L, Masini E, Granger HJ, Maggi CA, Geppetti P, Ledda F. Nitric oxide mediates angiogenesis in vivo and endothelial cell growth and migration in vitro promoted by substance P. J Clin Invest. 1994;94:2036-2044.
15. Bath PMW. The effect of nitric oxide–donating vasodilators on monocyte chemotaxis and intracellular cGMP concentrations in vitro. Eur J Clin Pharmacol. 1993;45:53-58. [Medline] [Order article via Infotrieve]
16. Majack RA, Clowes AW. Inhibition of vascular smooth muscle cell migration by heparin-like glycosaminoglycans. J Cell Physiol. 1984;118:253-256. [Medline] [Order article via Infotrieve]
17.
Murugesan G, Chisholm GM, Fox PL. Oxidized low
density lipoprotein inhibits the migration of aortic
endothelial cells in vitro. J
Cell Biol. 1993;120:1011-1019.
18.
Gordon D, Mohai LG, Schwartz SM. Induction of
polyploidy in cultures of neonatal rat aortic smooth muscle
cells. Circ Res. 1986;59:633-644.
19. Maragos CM, Morley D, Wink DA, Dunams TM, Saavedra JE, Hoffman A, Bove AA, Isaac L, Hrabie JA, Keefer LK. Complexes of NO with nucleophiles as agents for the controlled biological release of nitric oxide. J Med Chem. 1991;34:3242-3247. [Medline] [Order article via Infotrieve]
20. Radomski MW, Rees DD, Dutra A, Moncada S. S-nitroso-glutathione inhibits platelet activation in vitro and in vivo. Br J Pharmacol. 1992;107:745-749. [Medline] [Order article via Infotrieve]
21.
Gross SS, Levi R. Tetrahydrobiopterin synthesis:
an absolute requirement for cytokine-induced nitric
oxide generation by vascular smooth muscle. J
Biol Chem. 1992;267:25722-25729.
22.
Kontos HA, Wei EP. Hydroxyl
radical–dependent inactivation of guanylate cyclase in
cerebral arterioles by methylene blue and by LY83583.
Stroke. 1993;24:427-434.
23.
Stadler J, Curran RD, Ochoa JB, Harbrecht BG, Hoffman
RA, Simmons RL, Billiar TR. Effect of endogenous
nitric oxide on mitochondrial respiration of rat
hepatocytes in vitro and in vivo. Arch
Surg. 1991;126:186-191.
24. Hong D, Stevens P. The role of protein synthesis in the chemotaxis and chemiluminescence of human polymorphonuclear lymphocytes. Pharmacology. 1984;28:281-288. [Medline] [Order article via Infotrieve]
25.
Clowes AW, Clowes MM. Kinetics of cellular
proliferation after arterial injury, IV: heparin inhibits
rat smooth muscle mitogenesis and migration.
Circ Res. 1986;58:839-845.
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 I. Fishbein, I. S. Alferiev, O. Nyanguile, R. Gaster, J. M. Vohs, G. S. Wong, H. Felderman, I-W. Chen, H. Choi, R. L. Wilensky, et al. Bisphosphonate-mediated gene vector delivery from the metal surfaces of stents PNAS, January 3, 2006; 103(1): 159 - 164. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Shinohara, S. Kawashima, T. Yamashita, T. Takaya, R. Toh, T. Ishida, T. Ueyama, N. Inoue, K.-i. Hirata, and M. Yokoyama Xenogenic smooth muscle cell immunization reduces neointimal formation in balloon-injured rabbit carotid arteries Cardiovasc Res, November 1, 2005; 68(2): 249 - 258. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. W. Q. Moore and D. Y. Hui Apolipoprotein E inhibition of vascular hyperplasia and neointima formation requires inducible nitric oxide synthase J. Lipid Res., October 1, 2005; 46(10): 2083 - 2090. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. K. Krempl, R. Maas, K. Sydow, T. Meinertz, R. H. Boger, and J. Kahler Elevation of asymmetric dimethylarginine in patients with unstable angina and recurrent cardiovascular events Eur. Heart J., September 2, 2005; 26(18): 1846 - 1851. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Dashwood, K. Savage, A. Dooley, X. Shi-Wen, D. J. Abraham, and D. S.R. Souza Effect of Vein Graft Harvesting on Endothelial Nitric Oxide Synthase and Nitric Oxide Production Ann. Thorac. Surg., September 1, 2005; 80(3): 939 - 944. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Murata, M. Hori, S. Lee, A. Nakamura, K. Kohama, H. Karaki, and H. Ozaki Vascular Endothelium Has a Local Anti-Adenovirus Vector System and Glucocorticoid Optimizes Its Gene Transduction Arterioscler Thromb Vasc Biol, September 1, 2005; 25(9): 1796 - 1803. [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]
|
|
|
|
 |
|
 N. C. Browner, N. B. Dey, K. D. Bloch, and T. M. Lincoln Regulation of cGMP-dependent Protein Kinase Expression by Soluble Guanylyl Cyclase in Vascular Smooth Muscle Cells J. Biol. Chem., November 5, 2004; 279(45): 46631 - 46636. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kawashima and M. Yokoyama Dysfunction of Endothelial Nitric Oxide Synthase and Atherosclerosis Arterioscler Thromb Vasc Biol, June 1, 2004; 24(6): 998 - 1005. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. S. Do, E. Y. Kao, F. Ganaha, H. Minamiguchi, K. Sugimoto, J. Lee, C. J. Elkins, P. G. Amabile, M. D. Kuo, D. S. Wang, et al. In-Stent Restenosis Limitation with Stent-based Controlled-Release Nitric Oxide: Initial Results in Rabbits Radiology, February 1, 2004; 230(2): 377 - 382. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Dixit, D. Zhuang, B. Ceacareanu, and A. Hassid Treatment With Insulin Uncovers the Motogenic Capacity of Nitric Oxide in Aortic Smooth Muscle Cells: Dependence on Gab1 and Gab1-SHP2 Association Circ. Res., November 14, 2003; 93 (10): e113 - e123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-M. Lu, Y.-A. Ding, S.-J. Lin, W.-S. Lee, and H.-C. Tai Plasma levels of asymmetrical dimethylarginine and adverse cardiovascular events after percutaneous coronary intervention Eur. Heart J., November 1, 2003; 24(21): 1912 - 1919. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Creager, T. F. Luscher, F. Cosentino, and J. A. Beckman Diabetes and Vascular Disease: Pathophysiology, Clinical Consequences, and Medical Therapy: Part I Circulation, September 23, 2003; 108(12): 1527 - 1532. [Full Text] [PDF]
|
|
|
|
|
|
Y. Lin, A. C. Ceacareanu, and A. Hassid Nitric oxide-induced inhibition of aortic smooth muscle cell motility: role of PTP-PEST and adaptor proteins p130cas and Crk Am J Physiol Heart Circ Physiol, July 11, 2003; 285(2): H710 - H721. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Fernandez-Varo, J. Ros, M. Morales-Ruiz, P. Cejudo-Martin, V. Arroyo, M. Sole, F. Rivera, J. Rodes, and W. Jimenez Nitric Oxide Synthase 3-Dependent Vascular Remodeling and Circulatory Dysfunction in Cirrhosis Am. J. Pathol., June 1, 2003; 162(6): 1985 - 1993. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Zhang, Y. Yang, B. C. Kone, J. C. Allen, and A. M. Kahn Insulin-Stimulated Cyclic Guanosine Monophosphate Inhibits Vascular Smooth Muscle Cell Migration by Inhibiting Ca/Calmodulin-Dependent Protein Kinase II Circulation, March 25, 2003; 107(11): 1539 - 1544. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Yan, D. Kim, T. Aizawa, and B. C. Berk Functional Interplay Between Angiotensin II and Nitric Oxide: Cyclic GMP as a Key Mediator Arterioscler Thromb Vasc Biol, January 1, 2003; 23(1): 26 - 36. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Chang, B. Ceacareanu, M. Dixit, N. Sreejayan, and A. Hassid Nitric Oxide-Induced Motility in Aortic Smooth Muscle Cells: Role of Protein Tyrosine Phosphatase SHP-2 and GTP-Binding Protein Rho Circ. Res., September 6, 2002; 91(5): 390 - 397. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Shuhaiber, A. N. Evans, M. G. Massad, and A. S. Geha Mechanisms and future directions for prevention of vein graft failure in coronary bypass surgery Eur. J. Cardiothorac. Surg., September 1, 2002; 22(3): 387 - 396. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Sreejayan, Y. Lin, and A. Hassid NO Attenuates Insulin Signaling and Motility in Aortic Smooth Muscle Cells via Protein Tyrosine Phosphatase 1B-Mediated Mechanism Arterioscler Thromb Vasc Biol, July 1, 2002; 22(7): 1086 - 1092. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.P.M. Leeson, A.D. Hingorani, M.J. Mullen, N. Jeerooburkhan, M. Kattenhorn, T.J. Cole, D.P.R. Muller, A. Lucas, S.E. Humphries, and J.E. Deanfield Glu298Asp Endothelial Nitric Oxide Synthase Gene Polymorphism Interacts With Environmental and Dietary Factors to Influence Endothelial Function Circ. Res., June 14, 2002; 90(11): 1153 - 1158. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Beckman, M. A. Creager, and P. Libby Diabetes and Atherosclerosis: Epidemiology, Pathophysiology, and Management JAMA, May 15, 2002; 287(19): 2570 - 2581. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ryu, N. Takuwa, N. Sugimoto, S. Sakurada, S. Usui, H. Okamoto, O. Matsui, and Y. Takuwa Sphingosine-1-Phosphate, a Platelet-Derived Lysophospholipid Mediator, Negatively Regulates Cellular Rac Activity and Cell Migration in Vascular Smooth Muscle Cells Circ. Res., February 22, 2002; 90(3): 325 - 332. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Savvidou, P. J.T. Vallance, K. H. Nicolaides, and A. D. Hingorani Endothelial Nitric Oxide Synthase Gene Polymorphism and Maternal Vascular Adaptation to Pregnancy Hypertension, December 1, 2001; 38(6): 1289 - 1293. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Chandrasekar, S. Nattel, and J.-F. Tanguay Coronary artery endothelial protection after local delivery of 17{beta}-estradiol during balloon angioplasty in a porcine model: a potential new pharmacologic approach to improve endothelial function J. Am. Coll. Cardiol., November 1, 2001; 38(5): 1570 - 1576. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Vermeersch, Z. Nong, E. Stabile, O. Varenne, H. Gillijns, M. Pellens, N. Van Pelt, M. Hoylaerts, I. De Scheerder, D. Collen, et al. L-Arginine Administration Reduces Neointima Formation After Stent Injury in Rats by a Nitric Oxide-Mediated Mechanism Arterioscler Thromb Vasc Biol, October 1, 2001; 21(10): 1604 - 1609. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Brown, Y. Lin, and A. Hassid Requirement of protein tyrosine phosphatase SHP2 for NO-stimulated vascular smooth muscle cell motility Am J Physiol Heart Circ Physiol, October 1, 2001; 281(4): H1598 - H1605. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Wang, Z. Zhou, X. Zhou, K. Tarakji, E. J. Topol, and A. M. Lincoff Prevention of intimal hyperplasia with recombinant soluble P-selectin glycoprotein ligand-immunoglobulin in the porcine coronary artery balloon injury model J. Am. Coll. Cardiol., August 1, 2001; 38(2): 577 - 582. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. H. Kown, A. Yamaguchi, C. L. Jahncke, D. Miniati, S. Murata, J. Grunenfelder, M. L. Koransky, J. B. Rothbard, and R. C. Robbins L-arginine polymers inhibit the development of vein graft neointimal hyperplasia J. Thorac. Cardiovasc. Surg., May 1, 2001; 121(5): 971 - 980. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. D. Le Cras and I. F. McMurtry Nitric oxide production in the hypoxic lung Am J Physiol Lung Cell Mol Physiol, April 1, 2001; 280(4): L575 - L582. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Lembo, N. De Luca, C. Battagli, G. Iovino, A. Aretini, M. Musicco, G. Frati, F. Pompeo, C. Vecchione., and B. Trimarco A Common Variant of Endothelial Nitric Oxide Synthase (Glu298Asp) Is an Independent Risk Factor for Carotid Atherosclerosis Stroke, March 1, 2001; 32(3): 735 - 740. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. P. Cherla and R. K. Ganju Stromal Cell-Derived Factor 1{{alpha}}-Induced Chemotaxis in T Cells Is Mediated by Nitric Oxide Signaling Pathways J. Immunol., March 1, 2001; 166(5): 3067 - 3074. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-L. Niu, X. Yang, K. Hoshiai, K. Tanaka, S. Sawamura, Y. Koga, and H. Nakazawa Inducible Nitric Oxide Synthase Deficiency Does Not Affect the Susceptibility of Mice to Atherosclerosis but Increases Collagen Content in Lesions Circulation, February 27, 2001; 103(8): 1115 - 1120. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Sinnaeve, J.-D. Chiche, Z. Nong, O. Varenne, N. Van Pelt, H. Gillijns, D. Collen, K. D. Bloch, and S. Janssens Soluble Guanylate Cyclase {{alpha}}1 and {beta}1 Gene Transfer Increases NO Responsiveness and Reduces Neointima Formation After Balloon Injury in Rats via Antiproliferative and Antimigratory Effects Circ. Res., January 19, 2001; 88(1): 103 - 109. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Chandrasekar and J.-F. Tanguay Local delivery of 17-beta-estradiol decreases neointimal hyperplasia after coronary angioplasty in a porcine model J. Am. Coll. Cardiol., November 15, 2000; 36(6): 1972 - 1978. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Agata, R. Q. Miao, K. Yayama, L. Chao, and J. Chao Bradykinin B1 Receptor Mediates Inhibition of Neointima Formation in Rat Artery After Balloon Angioplasty Hypertension, September 1, 2000; 36(3): 364 - 370. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Sato, K. Nair, J. Hiddinga, N. L. Eberhardt, L. A. Fitzpatrick, Z. S. Katusic, and T. O'Brien eNOS gene transfer to vascular smooth muscle cells inhibits cell proliferation via upregulation of p27 and p21 and not apoptosis Cardiovasc Res, September 1, 2000; 47(4): 697 - 706. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Channon, H. Qian, and S. E. George Nitric Oxide Synthase in Atherosclerosis and Vascular Injury : Insights From Experimental Gene Therapy Arterioscler Thromb Vasc Biol, August 1, 2000; 20(8): 1873 - 1881. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Fukada, S. Schena, I. Tack, P. Ruiz, Y. Kurimoto, M. Pang, A. Aitouche, T. Abe, L. J. Striker, and S. M. Pham FK409, a Spontaneous Nitric Oxide Releaser, Attenuates Allograft Vasculopathy in a Rat Aortic Transplant Model Circ. Res., July 7, 2000; 87(1): 66 - 72. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Rudic, M. Bucci, D. Fulton, S. S. Segal, and W. C. Sessa Temporal Events Underlying Arterial Remodeling After Chronic Flow Reduction in Mice : Correlation of Structural Changes With a Deficit in Basal Nitric Oxide Synthesis Circ. Res., June 9, 2000; 86(11): 1160 - 1166. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Emanueli, M. B. Salis, J. Chao, L. Chao, J. Agata, K.-F. Lin, A. Munao, S. Straino, A. Minasi, M. C. Capogrossi, et al. Adenovirus-Mediated Human Tissue Kallikrein Gene Delivery Inhibits Neointima Formation Induced by Interruption of Blood Flow in Mice Arterioscler Thromb Vasc Biol, June 1, 2000; 20(6): 1459 - 1466. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ishigami, D. K. Swertfeger, M. S. Hui, N. A. Granholm, and D. Y. Hui Apolipoprotein E Inhibition of Vascular Smooth Muscle Cell Proliferation but Not the Inhibition of Migration Is Mediated Through Activation of Inducible Nitric Oxide Synthase Arterioscler Thromb Vasc Biol, April 1, 2000; 20(4): 1020 - 1026. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Kahn, J. C. Allen, C. L. Seidel, D. S. Lichtenberg, T. Song, and S. Zhang Insulin increases NO-stimulated guanylate cyclase activity in cultured VSMC while raising redox potential Am J Physiol Endocrinol Metab, April 1, 2000; 278(4): E627 - E633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kaul, B. Cercek, J. Rengstrom, X.-P. Xu, M. D. Molloy, P. Dimayuga, A. K. Parikh, M. C. Fishbein, J. Nilsson, T. B. Rajavashisth, et al. Polymeric-based perivascular delivery of a nitric oxide donor inhibits intimal thickening after balloon denudation arterial injury: role of nuclear factor-kappaB J. Am. Coll. Cardiol., February 1, 2000; 35(2): 493 - 501. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Chen, S. M. Kumar, C. L. Sahley, and K. J. Muller Nitric Oxide Influences Injury-Induced Microglial Migration and Accumulation in the Leech CNS J. Neurosci., February 1, 2000; 20(3): 1036 - 1043. [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]
|
|
|
|
|
|
A. D. Hingorani, C. F. Liang, J. Fatibene, A. Lyon, S. Monteith, A. Parsons, S. Haydock, R. V. Hopper, N. G. Stephens, K. M. O'Shaughnessy, et al. A Common Variant of the Endothelial Nitric Oxide Synthase (Glu298->Asp) Is a Major Risk Factor for Coronary Artery Disease in the UK Circulation, October 5, 1999; 100(14): 1515 - 1520. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Hassid, J. Yao, and S. Huang NO alters cell shape and motility in aortic smooth muscle cells via protein tyrosine phosphatase 1B activation Am J Physiol Heart Circ Physiol, September 1, 1999; 277(3): H1014 - H1026. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kibbe, T. Billiar, and E. Tzeng Inducible nitric oxide synthase and vascular injury Cardiovasc Res, August 15, 1999; 43(3): 650 - 657. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. E. MASON, P. CHANG, C. FALLERY, and M. RABINOVITCH Nitric oxide mediates LC-3-dependent regulation of fibronectin in ductus arteriosus intimal cushion formation FASEB J, August 1, 1999; 13(11): 1423 - 1434. [Abstract] [Full Text]
|
|
|
|
|
|
H. Qian, V. Neplioueva, G. A. Shetty, K. M. Channon, and S. E. George Nitric Oxide Synthase Gene Therapy Rapidly Reduces Adhesion Molecule Expression and Inflammatory Cell Infiltration in Carotid Arteries of Cholesterol-Fed Rabbits Circulation, June 15, 1999; 99(23): 2979 - 2982. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T.-c. Hsieh, G. Juan, Z. Darzynkiewicz, and J. M. Wu Resveratrol Increases Nitric Oxide Synthase, Induces Accumulation of p53 and p21WAF1/CIP1, and Suppresses Cultured Bovine Pulmonary Artery EndothelialCell Proliferation by Perturbing Progression through S and G2 Cancer Res., June 1, 1999; 59(11): 2596 - 2601. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. V. Sharma, E. Tan, S. Fang, M. V. Gurjar, and R. C. Bhalla NOS gene transfer inhibits expression of cell cycle regulatory molecules in vascular smooth muscle cells Am J Physiol Heart Circ Physiol, May 1, 1999; 276(5): H1450 - H1459. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Brown, X. Pan, and A. Hassid Nitric Oxide and C-Type Atrial Natriuretic Peptide Stimulate Primary Aortic Smooth Muscle Cell Migration via a cGMP-Dependent Mechanism : Relationship to Microfilament Dissociation and Altered Cell Morphology Circ. Res., April 2, 1999; 84(6): 655 - 667. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Le Tourneau, E. Van Belle, D. Corseaux, B. Vallet, G. Lebuffe, B. Dupuis, J.-M. Lablanche, E. McFadden, C. Bauters, and M. E. Bertrand Role of nitric oxide in restenosis after experimental balloon angioplasty in the hypercholesterolemic rabbit: effects on neointimal hyperplasia and vascular remodeling J. Am. Coll. Cardiol., March 1, 1999; 33(3): 876 - 882. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. J. Kullo, R. D. Simari, and R. S. Schwartz Vascular Gene Transfer : From Bench to Bedside Arterioscler Thromb Vasc Biol, February 1, 1999; 19(2): 196 - 207. [Full Text] [PDF]
|
|
|
|
|
|
S. Fang, R. V. Sharma, and R. C. Bhalla Enhanced Recovery of Injury-Caused Downregulation of Paxillin Protein by eNOS Gene Expression in Rat Carotid Artery : Mechanism of NO Inhibition of Intimal Hyperplasia? Arterioscler Thromb Vasc Biol, January 1, 1999; 19(1): 147 - 152. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-D. Chiche, S. M. Schlutsmeyer, D. B. Bloch, S. M. de la Monte, J. D. Roberts Jr., G. Filippov, S. P. Janssens, A. Rosenzweig, and K. D. Bloch Adenovirus-mediated Gene Transfer of cGMP-dependent Protein Kinase Increases the Sensitivity of Cultured Vascular Smooth Muscle Cells to the Antiproliferative and Pro-apoptotic Effects of Nitric Oxide/cGMP J. Biol. Chem., December 18, 1998; 273(51): 34263 - 34271. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Channon, H. Qian, V. Neplioueva, M. A. Blazing, E. Olmez, G. A. Shetty, S. A. Youngblood, J. Pawloski, T. McMahon, J. S. Stamler, et al. In Vivo Gene Transfer of Nitric Oxide Synthase Enhances Vasomotor Function in Carotid Arteries From Normal and Cholesterol-Fed Rabbits Circulation, November 3, 1998; 98(18): 1905 - 1911. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Varenne, S. Pislaru, H. Gillijns, N. Van Pelt, R. D. Gerard, P. Zoldhelyi, F. Van de Werf, D. Collen, and S. P. Janssens Local Adenovirus-Mediated Transfer of Human Endothelial Nitric Oxide Synthase Reduces Luminal Narrowing After Coronary Angioplasty in Pigs Circulation, September 1, 1998; 98(9): 919 - 926. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Poppa, J. K. Miyashiro, M. A. Corson, and B. C. Berk Endothelial NO Synthase Is Increased in Regenerating Endothelium After Denuding Injury of the Rat Aorta Arterioscler Thromb Vasc Biol, August 1, 1998; 18(8): 1312 - 1321. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Channon, H. Qian, S. A. Youngblood, E. Olmez, G. A. Shetty, V. Neplioueva, M. A. Blazing, and S. E. George Acute Host-Mediated Endothelial Injury After Adenoviral Gene Transfer in Normal Rabbit Arteries : Impact on Transgene Expression and Endothelial Function Circ. Res., June 29, 1998; 82(12): 1253 - 1262. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Yamamoto, M. Aoyagi, N. Fukai, Y. Matsushima, and K. Yamamoto Differences in Cellular Responses to Mitogens in Arterial Smooth Muscle Cells Derived From Patients With Moyamoya Disease Stroke, June 1, 1998; 29(6): 1188 - 1193. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J o. Koglin, T. Glysing-Jensen, J. S. Mudgett, and M. E. Russell Exacerbated Transplant Arteriosclerosis in Inducible Nitric Oxide–Deficient Mice Circulation, May 26, 1998; 97(20): 2059 - 2065. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Chen, G. Daum, R. Forough, M. Clowes, U. Walter, and A. W. Clowes Overexpression of Human Endothelial Nitric Oxide Synthase in Rat Vascular Smooth Muscle Cells and in Balloon-Injured Carotid Artery Circ. Res., May 4, 1998; 82(8): 862 - 870. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. R. Myers and M. A. Tanner Vascular Endothelial Cell Regulation of Extracellular Matrix Collagen : Role of Nitric Oxide Arterioscler Thromb Vasc Biol, May 1, 1998; 18(5): 717 - 722. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. B. Dey, N. J. Boerth, J. E. Murphy-Ullrich, P.-L. Chang, C. W. Prince, and T. M. Lincoln Cyclic GMP–Dependent Protein Kinase Inhibits Osteopontin and Thrombospondin Production in Rat Aortic Smooth Muscle Cells Circ. Res., February 9, 1998; 82(2): 139 - 146. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Ewing, D. V. Young, D. R. Janero, D. S. Garvey, and T. A. Grinnell Nitrosylated Bovine Serum Albumin Derivatives as Pharmacologically Active Nitric Oxide Congeners J. Pharmacol. Exp. Ther., November 1, 1997; 283(2): 947 - 954. [Abstract] [Full Text]
|
|
|
|
|
|
I. J. Kullo, R. S. Schwartz, V. J. Pompili, M. Tsutsui, S. Milstien, L. A. Fitzpatrick, Z. S. Katusic, and T. O'Brien Expression and Function of Recombinant Endothelial NO Synthase in Coronary Artery Smooth Muscle Cells Arterioscler Thromb Vasc Biol, November 1, 1997; 17(11): 2405 - 2412. [Abstract] [Full Text]
|
|
|
|
|
|
J.-L. Balligand and P. J. Cannon Nitric Oxide Synthases and Cardiac Muscle : Autocrine and Paracrine Influences Arterioscler Thromb Vasc Biol, October 1, 1997; 17(10): 1846 - 1858. [Abstract] [Full Text]
|
|
|
|
|
|
W. Aji, S. Ravalli, M. Szabolcs, X.-c. Jiang, R. R. Sciacca, R. E. Michler, and P. J. Cannon L-Arginine Prevents Xanthoma Development and Inhibits Atherosclerosis in LDL Receptor Knockout Mice Circulation, January 21, 1997; 95(2): 430 - 437. [Abstract] [Full Text]
|
|
|
|
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Y. Ryu, N. Takuwa, N. Sugimoto, S. Sakurada, S. Usui, H. Okamoto, O. Matsui, and Y. Takuwa Sphingosine-1-Phosphate, a Platelet-Derived Lysophospholipid Mediator, Negatively Regulates Cellular Rac Activity and Cell Migration in Vascular Smooth Muscle Cells Circ. Res., February 22, 2002; 90(3): 325 - 332. [Abstract] [Full Text] [PDF]
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