© 1999 American Heart Association, Inc.
Cellular Biology |
Increase in Prostaglandin E2 Production by Interleukin-1ß in Arterial Smooth Muscle Cells Derived From Patients With Moyamoya Disease
From the Department of Cell Biology (M.Y., M.A., N.F., K.Y.), Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo; and Department of Neurosurgery (M.A., Y.M.), Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
Correspondence to Kiyotaka Yamamoto, PhD, Department of Cell Biology, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173, Japan. E-mail kyama{at}tmig.or.jp
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Abstract |
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Abstract—Moyamoya disease is a progressive cerebrovascular occlusive disease that primarily affects children. The cause is unknown. We examined the production of prostanoids and the expression of cyclooxygenase-2 (COX-2) in cultured arterial smooth muscle cells (SMCs) derived from patients with moyamoya disease. Twelve moyamoya and 8 control cell strains were examined. The steady-state levels of prostanoids in the culture medium did not differ between moyamoya and control SMCs. When the cells were stimulated with interleukin-1ß (IL-1ß), prostaglandin E2 (PGE2) release into the medium was significantly greater from moyamoya SMCs than from control SMCs, whereas the amounts of prostacyclin and thromboxane B2 did not differ. IL-1ß–induced PGE2 production by moyamoya SMCs was completely blocked by the addition of indomethacin or NS-398. IL-1ß significantly stimulated cell migration and DNA synthesis in control SMCs but had an inhibitory effect on moyamoya SMCs. The inhibitory effects on the growth and migration of moyamoya SMCs were caused by excessive secretion of PGE2 and was reversed with indomethacin treatment. Immunofluorescence studies and Western blot analysis showed greater amounts of COX-2 protein expression in IL-1ß–stimulated moyamoya SMCs. These findings suggest that moyamoya SMCs respond to inflammatory stimuli to produce excess amounts of PGE2 through the activation of COX-2, which increases vascular permeability and decreases vascular tone. This facilitates the exposure of vessels to blood constituents and promotes the development of intimal thickening in moyamoya disease.
Key Words: interleukin • moyamoya disease • muscle, smooth • prostaglandin
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Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Moyamoya disease is an unusual form of chronic cerebrovascular occlusive disease that is characterized by progressive stenosis or occlusion at the distal ends of the bilateral internal carotid arteries.1 2 The disease peaks or primarily occurs during the first decade of life, and the neurological symptoms depend on the specific arteries that are occluded.3 The cause of the disease remains unknown. The findings that the incidence of the disease is highest in, but not confined to, the Japanese4 5 and that the condition is frequently familial6 7 suggest the involvement of a genetic factor in its pathogenesis. Previous reports and our findings suggest the involvement of systemic as well as intracranial arteries in moyamoya disease.8 9 10
The migration of medial smooth muscle cells (SMCs) and their
proliferation in the intimal layer may occur in response to injury of
the vascular wall.11 Recent evidence12
suggests a role for chronic inflammatory stimuli in SMC proliferation
in the thickened intima of patients with moyamoya disease. The
inflammatory response at the sites of injury and infiltration involves
the activation of many cytokines in the vascular wall,
including interleukin-1 (IL-1), interferon-
, and tumor necrosis
factor-
.11 13 14 The prostanoids represent a
diverse group of autocrine and paracrine hormones that are important
mediators of many cellular functions15 16 17 In the
vasculature, prostacyclin (prostaglandin
[PG]I2) and thromboxane
A2 act in opposite directions in the
maintenance of normal homeostasis and vascular tone.
PGE2 may increase vascular permeability and
decrease vascular tone.18 Nitric oxide (NO), which is
known to be an endothelium-derived relaxing factor,
regulates vascular tone and inhibits SMC migration.19 20
When stimulated by proinflammatory cytokines such as IL-1, SMCs
express cyclooxygenase-2 (COX-2) and produce
PGE2 and express inducible NO synthetase and
release NO.21 22 IL-1, which is produced mainly by induced
macrophages and monocytes, functions in the generation of
systemic and local responses to infection, injury, and immunologic
challenges. The unregulated local production of PGs and NO may
be responsible for various pathological processes in the vascular
wall.20 23 24 25 Based on the assumption that functional
alterations in vascular wall cells are involved in the development of
intimal thickening in moyamoya disease, we investigated cultured
SMCs derived from patients with moyamoya disease.26 27
We recently found that moyamoya SMCs show distinct migratory and
proliferative responses through an NO-independent pathway when
stimulated by IL-1.28 In the present study, we
examined prostanoid production and COX-2 expression in
IL-1ß–stimulated SMCs derived from patients with moyamoya
disease and compared the results with those in SMCs from age-matched
control subjects. We show that the distinct responses of moyamoya
SMCs to inflammatory stimuli may contribute to the pathological process
in the vascular wall of patients with moyamoya disease.
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Materials and Methods |
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Cell Culture
Arterial SMC strains from patients with moyamoya disease (HMSMC) and from control subjects (HCSMC) were established as described previously.26 We used 12 SMC strains from patients with moyamoya disease and 8 strains from control subjects (Table 1
).
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The cells were cultured in 5 mL of Eagle’s MEM (GIBCO) supplemented with 15% FBS (Biocell) at 37°C under humidified 5% CO2/95% air and subcultured at a 1:2 split ratio. For the present study, we used cells at 8 to 14 passages.29
Determination of Prostanoid Production
Medium was replaced with fresh medium containing 0.5% FBS and
500 U/mL IL-1ß (Otsuka Pharmaceutical) with or without 1 µg/mL
indomethacin (Sigma Chemical Co), a nonselective COX
inhibitor; 1 µmol/L NS-398 (BIOMOL Research
Laboratories), a COX-2–selective inhibitor30 ;
or 5 µmol/L arachidonic acid (AA; Sigma Chemical
Co), and the cells were incubated for 48 hours at 37°C.
PGE2, PGI2, and
thromboxane (TX)B2 secreted into the
medium were measured with the use of enzyme immunoassay kits for
PGE2, 6-keto-PGF1, and
TXB2 (Cayman Chemical), respectively.
Migration Assay
SMC migration was monitored in a microchemotaxis chamber (Neuro
Probe) with the use of polycarbonate membranes with 8-µm pores, as
described previously.28 Cell suspension was placed in the
upper compartment with or without indomethacin (1
µg/mL). The lower compartment contained MEM containing 2% FBS and
test reagents (500 U/mL IL-1ß and 0.4 to 200 nmol/L
PGE2; Paesel). The samples were incubated in a
CO2 incubator for 18 hours at 37°C.
Incorporation of 5-Bromo-2'-Deoxyuridine Into Cellular DNA
5-Bromo-2'-deoxyuridine (BrdU) incorporation was measured with
an immunoperoxidase technique (Amersham Corp), as previously
described.31 Quiescent SMCs were incubated in MEM
containing 0.5% FBS, test reagents, and a labeling regent (BrdU) for
48 hours. The test reagents were IL-1ß (500 U/mL),
indomethacin (1 µg/mL), and
PGE2 (0.4 to 200 nmol/L).
Immunocytochemistry
Quiescent SMCs were incubated with IL-1ß (500 U/mL) for 9
hours and fixed in acetone/methanol (1:1) at 4°C for 30 minutes. The
cells were preincubated with a 1:250 dilution of normal rabbit serum at
24°C for 30 minutes, with a 1:250 dilution of goat anti–COX-1 or
anti–COX-2 antibody (Santa Cruz Biotechnology) at 24°C for 1 hour,
and then with a 1:250 dilution of rhodamine-conjugated rabbit anti-goat
IgG (ICN Biomedicals) at 24°C for 45 minutes.
Western Blot Analysis
Western blot analysis was performed with 10%
acrylamide gels, as described previously.32
After blocking, membranes were incubated with a 1:250 dilution of goat
anti–COX-1 or anti–COX-2 antibody at 24°C for 1 hour and then with
a 1:500 dilution of peroxidase-conjugated rabbit anti-goat IgG (ICN
Biomedicals) at 24°C for 45 minutes.
Statistical Analysis
Values are given as mean±SD. Differences in data between groups
were assessed with the use of an unpaired t test. A value of
P<0.05 was considered statistically significant.
An expanded Materials and Methods section is available online at http://www.circresaha.org.
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Results |
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Prostanoid Production in Culture Medium of Arterial SMCs Derived From Patients With Moyamoya Disease
The steady-state levels of PGE2, PGI2, and TXB2 production in HMSMC strains were low and not significantly different from those in HCSMC strains (Figure 1
). Although IL-1ß promoted both
PGE2 and PGI2
production in the culture medium of HCSMC and HMSMC strains,
the levels of IL-1ß–induced PGE2
production in HMSMC (44.8-fold) were significantly greater than
those in HCSMC (10.2-fold) strains. In contrast, the levels of
IL-1ß–induced PGI2 production did not
differ significantly between HCSMC and HMSMC strains (Figure 1).
IL-1ß did not stimulate TXB2 production
by either the HCSMC or HMSMC strain. The addition of
indomethacin (1 µg/mL) completely blocked
IL-1ß–induced prostanoid production by both HMSMC and HCSMC
strains (Figure 1). The simultaneous addition of
NS-398 (1 µmol/L) with the cytokine completely
suppressed PGE2 and PGI2
production by both HMSMC and HCSMC strains (Figure 1).
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We then compared the conversion of exogenous AA (5 µmol/L) by
arterial SMCs from patients with moyamoya disease and
from control subjects. As shown in Figure 2, PGE2
production by HMSMC strains was clearly stimulated by the
addition of AA, but the amount did not differ significantly from that
produced by control strains (Figure 2). The AA-stimulated
PGE2 production in HMSMC strains was
significantly increased by IL-1ß compared with that in HCSMC
strains.
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Cell Migration and DNA Synthesis
The number of migrating cells in serum-deficient medium without
test mitogens (controls) did not differ between HCSMC (80.4±17.2) and
HMSMC (81.1±11.1) strains. IL-1ß stimulated cell migration in HCSMC
strains, although it significantly inhibited migration in HMSMC strains
(Table 2). IL-1ß also stimulated BrdU
incorporation into cellular DNA in control SMCs but had a rather
inhibitory effect on DNA synthesis in moyamoya SMCs
(Table 2). The basal labeling indices (controls) were
17.0±4.8% for HCSMC strains and 18.4±5.0% for HMSMC strains
(P=NS). When prostanoid synthesis was inhibited with
indomethacin, IL-1ß significantly stimulated cell
migration and BrdU incorporation in both HMSMC and HCSMC strains (Table 2). High concentrations (20 to 200 nmol/L) of exogenous
PGE2 induced the inhibition of
IL-1ß–stimulated cell migration and DNA synthesis in HCSMC and HMSMC
strains, but lower concentrations (0.4 to 4 nmol/L) had no detectable
inhibitory effects (Table 2). The higher
PGE2 concentrations correspond to those produced
by IL-1ß–stimulated HMSMC, and the lower concentrations correspond
to those produced by IL-1ß–stimulated HCSMC (Figure 1
).
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COX-2 Expression
We examined the expression of COX-1 and COX-2 proteins in cultured
arterial SMCs through
immunofluorescence study. No positive
immunostaining was found in both moyamoya and
control SMCs in the absence of the primary antibody or in the nonimmune
goat IgG (Figure 3, A and B). COX-2
protein was hardly detected in moyamoya and control SMCs grown to
confluence (Figure 3, C and D). IL-1ß stimulated the
expression of COX-2 protein in both moyamoya and control SMCs
(Figure 3, E and F); however, the increase in the number of
COX-2–positive cells was significantly (P<0.001) greater
in moyamoya SMCs (16.5±2.6%) than in control SMCs (5.3±2.1%).
In contrast, COX-1 immunoreactivity did not differ between moyamoya
(6.5±3.2%) and control (4.8±2.3%) SMCs in the presence of IL-1ß
and between moyamoya (5.9±3.7%) and control (5.0±1.8%) SMCs in
the absence of IL-1ß.
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Immunoblot analysis showed that the expression of
COX-2 protein was hardly detected in homogenates of
moyamoya and control SMCs in the absence of IL-1ß (Figure 4). The immunoreactive band to COX-2
increased clearly in both moyamoya and control SMCs in the presence
of IL-1ß, although the expression of COX-1 protein was not stimulated
by IL-1ß (Figure 4). The relative density of the COX-2 protein
in moyamoya cell strains was significantly (P<0.001)
higher than that in control cell strains (Figure 4).
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Discussion |
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Previous studies3 33 have suggested that moyamoya disease is an acquired disorder in which both an immunologic vascular reaction and subsequent inflammation play important roles. Recent evidence12 indicates that inflammatory stimuli and the subsequent response of inflammatory cells may produce a proliferative response in SMCs in the thickened intima of patients with moyamoya disease. In the present study, we examined the production of prostanoids, which act as mediators that modulate vascular functions when stimulated by proinflammatory cytokines such as IL-1,19 34 35 in arterial SMCs derived from patients with moyamoya disease. IL-1ß stimulates PGE2 and PGI2 production in both moyamoya and control SMCs. When stimulated by IL-1ß, the levels of PGI2 production do not differ between moyamoya and control SMCs. However, the level of IL-1ß–stimulated PGE2 production by moyamoya SMCs is significantly greater than that by control SMCs. NO stimulated by IL-1 also acts as a mediator that modulates vascular functions,19 34 35 but IL-1–induced NO production is found to be almost the same in HMSMC and HCSMC strains.28
IL-1 is a multipotent inflammatory mediator that may play a central role in vascular pathophysiology.36 37 Previous reports indicate that IL-1 stimulates the migration and proliferation of aortic SMCs,38 39 whereas others have shown it to lack mitogenic effects on vascular SMCs.34 40 IL-1 reportedly stimulates cells to produce platelet-derived growth factor-AA,39 a positively affecting mitogen, and stimulates cells to produce PGE234 and NO,19 41 both of which have inhibitory effects on cell mitogenesis. As we reported recently,28 IL-1ß was found to significantly stimulate cell migration and DNA synthesis in control SMCs, whereas it inhibits cell migration and DNA synthesis in moyamoya SMCs. The inhibitory effect of IL-1ß on cell migration and DNA synthesis in moyamoya SMCs corresponds to the elevated levels of PGE2, but not NO, production. Indomethacin treatment suppresses PG synthesis and results in stimulatory effects by IL-1ß on cell migration and DNA synthesis in moyamoya SMCs. Furthermore, the higher concentrations of exogenous PGE2, corresponding to the endogenous PGE2 levels produced by IL-1ß–stimulated moyamoya SMCs, in the presence of indomethacin inhibits IL-1ß–stimulated migration and DNA synthesis in both moyamoya and control SMCs. Taken together, it is most likely that IL-1ß fails to stimulate the migration and proliferation of moyamoya SMCs due to excessive autocrine PGE2 production from moyamoya SMCs.
The synthesis of PGs that have diverse biological effects on the vasculature is regulated by two successive metabolic steps: the release of AA from membranous phospholipids and its conversion to PGs.16 17 Two COX isoforms, COX-1 and COX-2, are the key enzymes that convert AA to PGs. COX-1 is constitutively expressed in most tissues. In healthy vessels, PGI2, which is a protective, "antiatherogenic" mediator, is formed predominantly in the endothelial layer via the actions of constitutive COX-1.42 In contrast, COX-2 is undetectable under physiological conditions but is markedly induced by several cytokines and growth factors in vascular cells.43 44 COX-2 limits the proliferation of human vascular SMCs.45 COX-2 is thought to be involved in the overproduction of prostanoids under pathological conditions such as acute and chronic inflammatory disorders and appears to be expressed only by specific stimulatory events.17 46 Studies in animals show that vessels damaged by angioplasty or pinch express COX-2, an event that may account for an increased release of protective PGI2.47 Bishop-Bailey et al48 show that IL-1 induces COX-2 in human vessels, with a pattern of prostanoid release of PGE2>PGI2>TXB2. The formation of PGE2 is mediated primarily by IL-1ß–induced COX-2 in SMCs and macrophages.21 22 In the present study, protective PGI2 is released predominantly in IL-1ß–stimulated control SMCs. The release of PGI2 may represent an endogenous defense mechanism against endothelial damage.48 In contrast, the expression of COX-2 protein and subsequent release of PGE2 are significantly up-regulated in IL-1ß–stimulated moyamoya SMCs compared with control SMCs. The conversion of exogenous AA into PGE2 by moyamoya SMCs in the presence of IL-1ß is significantly greater than that by control SMCs but does not differ between SMCs in the absence of IL-1ß. IL-1ß–induced prostanoid production by both HMSMC and HCSMC strains is completely blocked by the addition of NS-398 (1 µmol/L), a COX-2–selective inhibitor. Our findings strongly suggest that inflammatory stimuli and the subsequent inflammatory cell response stimulate the overproduction of PGE2 through an IL-1–induced COX-2 pathway in SMCs in moyamoya disease.
PGs of the E series are thought to modulate vasodilation and vascular permeability.18 49 50 51 The excessive amounts of PGE2 released from moyamoya arterial SMCs through COX-2 activation by inflammatory stimuli may increase vascular permeability and decrease vascular tone, facilitating exposure of the vessels to blood constituents, including growth factors and cytokines that might induce and promote the development of intimal thickening in moyamoya disease. The excessive amounts of PGE2 also inhibit the migration and proliferation of SMCs that might be necessary for the rapid repair of vascular wall injury, resulting in the continued increase in vascular permeability and facilitating the prolonged exposure of the vessels to blood constituents. The continued increase in vascular permeability may be much more important in neointimal accumulation than the exposure to excess individual growth factors.52 In addition, PGE2 and IL-1 are potent stimulators of angiogenesis,53 54 55 and they induce the expression of vascular endothelial cell growth factor, which stimulates both angiogenesis and vascular permeability.56 57 The induction of vascular endothelial cell growth factor by PGE2 and IL-1 may be an important mechanism in inflammatory angiogenesis.56 PGE2 and IL-1 may directly or indirectly play an important role in angiogenesis in moyamoya disease.
The mechanism of the specific response of moyamoya SMCs to IL-1ß is presently unknown. The distinct increase in PGE2, but not NO, production in moyamoya SMCs may indicate altered intracellular signaling pathways by which IL-1 induces NO and PG synthesis. Recent findings demonstrate that COX-2–selective inhibitors have excellent anti-inflammatory properties.17 Our findings suggest a possible interaction between the immune system and the vessel wall in moyamoya disease and serve as a basis for the clinical use of nonsteroidal anti-inflammatory drugs in the treatment of moyamoya disease.
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Acknowledgments |
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This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture, Japan. We thank Dr Margaret Dooley Ohto for reviewing the manuscript. We thank Naofumi Yamamoto (Nippon Medical School) for technical support on enzyme immunoassay.
Received July 12, 1999; accepted September 1, 1999.
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References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
1. Kudo T. Spontaneous occlusion of the circle of Willis: a disease apparently confined to Japanese. Neurology. 1968;18:485–496.
2. Nishimoto A, Takeuchi S. Abnormal cerebrovascular network related to the internal carotid arteries. J Neurosurg. 1968;29:255–260.[Medline] [Order article via Infotrieve]
3.
Suzuki J, Kodama N. Moyamoya disease: a review.
Stroke. 1983;14:104–109.
4.
Lee MLK, Cheung EMT. Moyamoya disease as a cause
of subarachnoid hemorrhage in Chinese.
Brain. 1973;96:623–628.
5. Iivanainen M, Vuolio M, Halonen V. Occlusive disease of intracranial main arteries with collateral networks (moyamoya disease) in adults. Acta Neurol Scand. 1973;49:307–322.[Medline] [Order article via Infotrieve]
6.
Kitahara T, Ariga N, Yamaura A, Makino H, Maki Y.
Familial occurrence of moyamoya disease: report of three Japanese
families. J Neurol Neurosurg Psychiatry. 1979;42:208–214.
7. Houkin K, Tanaka N, Takahashi A, Kamiyama H, Abe H, Kajii N. Familial occurrence of moyamoya disease: magnetic resonance angiography as a screening test for high-risk subjects. Childs Nerv Syst. 1994;10:421–425.[Medline] [Order article via Infotrieve]
8. Haltia M, Iivanainen M, Majuri H, Puranen M. Spontaneous occlusion of the circle of Willis (moyamoya syndrome). Clin Neuropathol. 1982;1:11–22.[Medline] [Order article via Infotrieve]
9. Halley SE, White WB, Ramsby GR, Voytovich AE. Renovascular hypertension in moyamoya syndrome: therapeutic response to percutaneous transluminal angioplasty. Am J Hypertens. 1988;1:348–352.[Medline] [Order article via Infotrieve]
10.
Aoyagi M, Fukai N, Yamamoto M, Nakagawa K, Matsushima
Y, Yamamoto K. Early development of intimal thickening in superficial
temporal arteries in patients with moyamoya disease.
Stroke. 1996;27:1750–1754.
11. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993;362:801–809.[Medline] [Order article via Infotrieve]
12.
Masuda J, Ogata J, Yutani C. Smooth muscle cell
proliferation and localization of macrophages and T cells in
the occlusive intracranial major arteries in moyamoya disease.
Stroke. 1993;24:1960–1967.
13.
Hansson GK, Holm J. Interferon- inhibits
arterial stenosis after injury.
Circulation. 1991;84:1266–1272.
14. Dower SK, Sims JE, Cerretti DP, Bird TA. The interleukin-1 system: receptors, ligands and signals. Mol Biol Immunol. 1992;51:33–64.
15. DeWitt DL. Prostaglandin endoperoxide synthase: regulation of enzyme expression. Biochim Biophys Acta. 1991;1083:121–134.[Medline] [Order article via Infotrieve]
16. Smith WL, Marnett LJ. Prostaglandin endoperoxide synthase: structure and catalysis. Biochim Biophys Acta. 1991;1083:1–17.[Medline] [Order article via Infotrieve]
17. DeWitt D, Smith LS. Yes, but do they still get headaches? Cell. 1995;83:345–348.[Medline] [Order article via Infotrieve]
18. Okiji T, Morita I, Suda H, Murota S. Pathophysiological roles of arachidonic acid metabolites in rat dental pulp. Proc Finnish Dent Soc. 1992;1:433–438.
19. Dubey RK, Jackson EK, Lüscher TF. Nitric oxide inhibits angiotensin II-induced migration of rat aortic smooth muscle cell: role of cyclic-nucleotides and angiotensin1 receptors. J Clin Invest. 1995;96:141–149.
20. Griendling KK, Alexander RW. Endothelial control of the cardiovascular system: recent advances. FASEB J. 1996;10:283–292.[Abstract]
21. Belvisi MG, Saunders MA, Haddad E-B, Hirst SJ, Yacoub MH, Barnes PJ, Mitchell JA. Induction of cyclo-oxygenase-2 by cytokines in human cultured airway smooth muscle cells: novel inflammatory role of this cell type. Br J Pharmacol. 1997;120:910–916.[Medline] [Order article via Infotrieve]
22. Matsumoto H, Naraba H, Murakami M, Kudo I, Yamaki K, Ueno A, Oh-ishi S. Concordant induction of prostaglandin E2 synthase with cyclooxygenase-2 leads preferred thromboxane and prostaglandin D2 in lipopolysaccharide-stimulated rat peritoneal macrophage. Biochem Biophys Res Commun. 1997;230:110–114.[Medline] [Order article via Infotrieve]
23. Albrightson CR, Baenziger NL, Needleman P. Exaggerated human vascular cell prostaglandin biosynthesis mediated by monocytes: role of monokines and interleukin 1. J Immunol. 1985;135:1872–1877.[Abstract]
24.
Warner SJC, Auger KR, Libby P. Human interleukin 1
induces interleukin 1 gene expression in human vascular smooth muscle
cells. J Exp Med. 1987;165:1316–1331.
25. 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.
26. Aoyagi M, Fukai N, Sakamoto H, Shinkai T, Matsushima Y, Yamamoto M, Yamamoto K. Altered cellular responses to serum mitogens, including platelet-derived growth factor, in cultured smooth muscle cells derived from arteries of patients with moyamoya disease. J Cell Physiol. 1991;147:191–198.[Medline] [Order article via Infotrieve]
27. Aoyagi M, Fukai N, Matsushima Y, Yamamoto M, Yamamoto K. Kinetics of 125I-PDGF binding and down-regulation of PDGF receptor in arterial smooth muscle cells derived from patients with moyamoya disease. J Cell Physiol. 1993;154:281–288.[Medline] [Order article via Infotrieve]
28.
Yamamoto M, Aoyagi M, Fukai N, Matsushima Y, Yamamoto
K. Differences in cellular responses to mitogens in
arterial smooth muscle cells derived from patients with
moyamoya disease. Stroke. 1998;29:1188–1193.
29. Fukai N, Aoyagi M, Yamamoto M, Sakamoto H, Ogami K, Matsushima Y, Yamamoto K. Human arterial smooth muscle cell strains derived from patients with moyamoya disease: changes in biological characteristics and proliferative response during cellular aging in vitro. Mech Ageing Dev. 1994;75:21–33.[Medline] [Order article via Infotrieve]
30. Futaki N, Takahashi S, Yokoyama M, Arai I, Higuchi S, Otomo S. NS-398, a new anti-inflammatory agent, selectively inhibits prostaglandin G/H synthetase/cyclooxygenase (COX-2) activity in vitro. Prostaglandins. 1994;47:55–59.[Medline] [Order article via Infotrieve]
31. Yamamoto M, Fujita K, Shinkai T, Yamamoto K, Noumura T. Identification of the phenotypic modulation of rabbit arterial smooth muscle cells in primary culture by flow cytometry. Exp Cell Res. 1992;198:43–51.[Medline] [Order article via Infotrieve]
32. Yamamoto K, Aoyagi M, Yamamoto M. Changes in elastin-binding proteins during the phenotypic transition of rabbit arterial smooth muscle cells in primary culture. Exp Cell Res. 1995;218:339–345.[Medline] [Order article via Infotrieve]
33.
Kitahara T, Okumura K, Semba A, Yamaura A, Makino H.
Genetic and immunologic analysis on moya-moya. J
Neurol Neurosurg Psychiatry. 1982;45:1048–1052.
34. Libby P, Warner SJC, Friedman GB. Interleukin 1: a mitogen for human vascular smooth muscle cells that induces the release of growth-inhibitory prostanoids. J Clin Invest. 1988;81:487–498.
35. Fukuo K, Inoue T, Morimoto S, Nakahashi T, Yasuda O, Kitano S. Nitric oxide mediates cytotoxicity and basic fibroblast growth factor release in cultured vascular smooth muscle cells: a possible mechanism of neovascularization in atherosclerotic plaques. J Clin Invest. 1995;95:669–676.
36. Libby P, Hansson GK. Biology of disease: involvement of the immune system in human atherogenesis: current knowledge and unanswered questions. Lab Invest. 1991;64:5–15.[Medline] [Order article via Infotrieve]
37. Dinarello CA. The biology of interleukin-1. Mol Biol Immunol. 1992;51:1–32.
38. Nomoto A, Mutoh S, Hagihara H, Yamaguchi I. Smooth muscle cell migration induced by inflammatory cell products and its inhibition by a potent calcium antagonist, nilvadipine. Atherosclerosis. 1988;72:213–219.[Medline] [Order article via Infotrieve]
39.
Raines EW, Dower SK, Ross R. Interleukin-1
mitogenic activity for fibroblasts and smooth muscle cells
is due to PDGF-AA. Science. 1989;243:393–396.
40.
Libby P, Wyler DJ, Janicka MW, Dinarello CA.
Differential effects of human interleukin-1 on growth of human
fibroblasts and vascular smooth muscle cells.
Arteriosclerosis. 1985;5:186–191.
41.
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.
42.
Mitchell JA, Akarasereenont P, Thiemermann C, Flower
RJ, Vane JR. Selectivity of nonsteroidal antiinflammatory drugs as
inhibitors of constitutive and inducible
cyclooxygenase. Proc Natl Acad Sci
U S A. 1993;90:11693–11697.
43.
Hla T, Neilson K. Human
cyclooxygenase-2 cDNA. Proc Natl Acad Sci
U S A. 1992;89:7384–7388.
44.
Rimarachin JA, Jacobson JA, Szabo P, Maclouf J,
Creminon C, Weksler BB. Regulation of
cyclooxygenase-2 expression in aortic smooth muscle
cells. Arterioscler Thromb. 1994;14:1021–1031.
45. Bornfeldt KE, Campbell JS, Koyama H, Argast GM, Leslie CC, Raines EW, Krebs EG, Ross R. The mitogen-activated protein kinase pathway can mediate growth inhibition and proliferation in smooth muscle cells: dependence on the availability of downstream targets. J Clin Invest. 1997;100:875–885.[Medline] [Order article via Infotrieve]
46. Vane J. Towards a better aspirin. Nature. 1994;367:215–216.[Medline] [Order article via Infotrieve]
47. Mitchell JA, Larkin S, Williams TJ. Cyclooxygenase-2: regulation and relevance in inflammation. Biochem Pharmacol. 1995;50:1535–1542.[Medline] [Order article via Infotrieve]
48.
Bishop-Bailey D, Pepper JR, Haddad E-B, Newton R,
Larkin SW, Mitchell JA. Induction of
cyclooxygenase-2 in human saphenous vein and
internal mammary artery. Arterioscler Thromb Vasc Biol. 1997;17:1644–1648.
49. Williams TJ, Peck MJ. Role of prostaglandin-mediated vasodilatation in inflammation. Nature. 1977;270:530–532.[Medline] [Order article via Infotrieve]
50. Lock JE, Olley PM, Coceani F. Direct pulmonary vascular responses to prostaglandins in the conscious newborn lamb. Am J Physiol. 1980;238:H631–H638.
51.
Lockette WE, Webb RC, Bohr DF.
Prostaglandins and potassium relaxation in vascular smooth
muscle of the rat: the role of Na-K ATPase. Circ Res. 1980;46:714–720.
52.
Lazarous DF, Shou M, Scheinowitz M, Hodge E, Thirumurti
V, Kitsiou AN, Stiber JA, Lobo AD, Hunsberger S, Guetta E, Epstein SE,
Unger EF. Comparative effects of basic fibroblast growth factor and
vascular endothelial growth factor on coronary
collateral development and the arterial response to injury.
Circulation. 1996;94:1074–1082.
53. Ziche M, Jones J, Gullino PM. Role of prostaglandin E1 and copper in angiogenesis. J Natl Cancer Inst. 1982;69:475–482.
54.
BenEzra D, Hemo I, Maftzir G. In vivo angiogenic
activity of interleukins. Arch Ophthalmol. 1990;108:573–576.
55. Fan TP, Hu DE, Guard S, Gresham GA, Watling KJ. Stimulation of angiogenesis by substance P and interleukin-1 in the rat and its inhibition by NK1 or interleukin-1 receptor antagonists. Br J Pharmacol. 1993;110:43–49.[Medline] [Order article via Infotrieve]
56. Ben-Av P, Crofford LJ, Wilder RL, Hla T. Induction of vascular endothelial growth factor expression in synovial fibroblasts by prostaglandin E and interleukin-1: a potential mechanism for inflammatory angiogenesis. FEBS Lett. 1995;372:83–87.[Medline] [Order article via Infotrieve]
57.
Li J, Perrella MA, Tsai J-C, Yet S-F, Hsieh C-M,
Yoshizumi M, Patterson C, Endege WO, Zhou F, Lee M-E. Induction of
vascular endothelial growth factor gene expression by
interleukin-1ß in rat aortic smooth muscle cells. J
Biol Chem. 1995;270:308–312.
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