© 2000 American Heart Association, Inc.
Brief Reviews |
Retinoids and Arterial Smooth Muscle Cells
From the Department of Pathology, University of Geneva-CMU, Geneva, Switzerland.
Correspondence to Prof Giulio Gabbiani, Department of Pathology, University of Geneva-CMU, 1 Rue Michel Servet, 1211 Geneva 4/Switzerland. E-mail Giulio.Gabbiani{at}medecine.unige.ch (Arterioscler Thromb Vasc Biol. 2000;20:1882-1888.)
Key Words: 
-smooth muscle actin • myofibroblast • atheroma • wound healing • TGF-ß
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Introduction |
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 Top Introduction RA and SMC LineageRA and SMC Biological...RA and SMC Gene...Conclusions and PerspectivesReferences |
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Retinoic acid (RA), the active metabolite of vitamin A, is a crucial signaling molecule during vertebrate development and plays key roles in establishing cell lineages as well as in cell differentiation and proliferation.1 RA has been shown to influence the expression of many genes (see the Table
) through interactions
between RA receptors (RARs) and the RA response element (RARE) located
in promoter regions.42 43 RARs, transducers of the RA
signal at the gene expression level, are members of the nuclear
receptor superfamily. Essentially 2 subfamilies of nuclear receptor are
known to function as RA-dependent transcription factors: the RARs and
the retinoid X receptors (RXRs).44 These
receptors, in the form of homodimers or heterodimers, recognize
response elements located in the promoter regions of target genes. For
each subfamily, 3 different genes (RAR-, -ß, and -
; RXR-,
-ß, and -) generate multiple isoforms with specific patterns of
expression in both the embryo and adult, suggesting that they perform
specific functions in the control of RA target genes.45
The uptake, transport, and metabolism of
all-trans retinol is regulated by the cellular
retinol-binding proteins (CRBP I and CRBP II), whereas the cellular
RA-binding proteins (CRABP I and CRABP II) exert the same function for
RA.1 Unlike RARs, retinoid-binding proteins modulate the
effect of RA by regulating its intracellular level. Several lines of
evidence indicate that CRBPs and CRABPs have distinct
physiological roles. CRBPs provide the substrate
for RA biosynthesis,46 whereas CRABPs are substrates for
RA catabolism.47 Retinoids have not been extensively
studied with regard to smooth muscle cell (SMC) biology. Their role in
establishing SMC lineages has long been reported, but their influence
on SMC function and their potential therapeutic use for vascular
proliferative disorders are only starting to be appreciated. This
review summarizes some of these recent advances.
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RA and SMC Lineage |
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TopIntroductionRA and SMC LineageRA and SMC Biological...RA and SMC Gene...Conclusions and PerspectivesReferences |
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RA has a teratogenic effect when applied during critical times of embryonic development.48 Both the lack of and excess RA may damage embryonic structures, including the cardiovascular apparatus.49 RA induces cardiac malformations,50 51 sharing effects with neural crest ablation.52 The neural crest is a transient, ectodermal structure of the vertebrate embryo containing cells that develop into various lineages. The cardiac subset of neural crest cells participates in the formation of the media of large arteries53 54 in combination with cells originating from the lateral mesoderm–derived mesenchyme.55 SMCs isolated from the thoracic aorta (derived from the neural crest) and abdominal aorta (derived from the mesoderm) of chick embryo and placed in culture differ morphologically: ectodermal cells have an epithelioid shape and grow in a monolayer, whereas mesodermal SMCs display the typical "hill-and-valley" growth pattern (see the section below on RA and SMC Biological Features).56 However, analysis of SMC differentiation markers (eg,
-SM actin, SM myosin, SM-22,
desmin, and calponin) in both cell types reveals similar expression
levels.56 A feature of neural crest–derived SMCs is their ability to be influenced by RA: on one hand, RA modulates differentiation of cardiac neural crest cells57 and on the other hand, neural crest–derived SMCs express RARs and binding proteins.58 59 Recent studies on ductus arteriosus development have shed new light on the action of RA on neural crest–derived SMCs. The ductus arteriosus connects the pulmonary artery and the aorta in the fetal circulation; it arises from the left sixth aortic arch, which is essentially composed of neural crest–derived SMCs.54 At birth, closure of the ductus arteriosus is caused by the formation of an important intimal thickening followed by vessel constriction. SMCs of the ductus arteriosus exhibit an advanced differentiation of the contractile apparatus compared with those of adjacent large vessels.60 In particular, the SM myosin heavy-chain isoform found in vessels after birth (SM2) is already expressed in the media of the ductus arteriosus before birth.61 Colbert et al62 have generated transgenic mice carrying an RARE-lacZ transgene expressing ß-galactosidase in response to endogenous RA. This reporter gene is specifically activated in SMCs of the ductus arteriosus during embryonic and neonatal development and is colocalized with SM2. Taken together, these results suggest that in the developing ductus arteriosus, RA acts as a signal promoting the differentiation of a subset of neural crest–derived SMCs.
Other evidence suggesting interactions between RA and SMC lineage have
arisen from studies on differentiation of embryonal carcinoma cells.
Embryonal carcinoma cells can be induced to differentiate in vitro into
a variety of cell types by treatment with different concentrations of
RA.63 At low RA concentrations, they differentiate into
fibroblast-like cells63 that express high levels of -SM
actin and SM myosin heavy chains and thus, resemble vascular
SMCs.64 During RA-induced differentiation of P19 embryonal
carcinoma cells, -SM actin and CRBP are rapidly
expressed.65 This CRBP induction occurs at RA
concentrations that support embryonal carcinoma cell differentiation
into SMCs. Increased levels of CRBP are also observed during F9
embryonal carcinoma cell differentiation induced by RA.66
Another cell line (9E11G), derived from RA-treated P19s, permanently
expresses multiple characteristics of differentiated SMCs, including
-SM actin and SM myosin heavy-chain expression and functional
responses to contractile agonists.67 More generally, it
appears that induction of RA-responsive genes is a prerequisite for
proper embryonal carcinoma cell differentiation, because a mutation
affecting the RAR- gene of the P19 mutant clone RAC65 blocks the
induction of RA-responsive genes as well as RA-induced
differentiation.68 69 The fact that a number of genes
expressed by differentiated SMCs appear after RA treatment argues in
favor of the assumption that RA is a key molecule in SMC
differentiation.
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RA and SMC Biological Features |
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TopIntroductionRA and SMC LineageRA and SMC Biological...RA and SMC Gene...Conclusions and PerspectivesReferences |
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Historically, the first description of distinct SMC phenotypes has been achieved by the identification of contractile and synthetic cells, the first being typical of differentiated arteries and the second, typical of developing and/or pathological arteries.70 71 Moreover, when arterial SMCs from adult animals are placed in culture, they switch their phenotype from contractile to synthetic. It is generally accepted that contractile and synthetic phenotypes can modulate from one to the other.70 71 A further step in the establishment of SMC heterogeneity has been the characterization of spindle and epithelioid phenotypes.56 72 73 74 These SMC subtypes, studied mostly in the rat, have been isolated from different arterial locations or from the same location of animals at different ages, and they exhibit distinct features: (1) the classic "hill-and-valley" growth pattern for the spindle-shape phenotype that is usually obtained from the normal adult media and (2) growth as a contact-inhibited monolayer for the epithelioid phenotype that has been first and is usually isolated from the intimal thickening induced 15 days after endothelial injury (IT15).74 75 76 It is accepted that spindle and epithelioid phenotypes permanently maintain their features in culture.75 76 77 Moreover, when SMCs are cloned from the aortic media or from IT15 cells, both phenotypes are retrieved and again remain stable during culture conditions.78 However, the proportion of clones exhibiting these phenotypes differs according to their origin, with the media yielding a majority of spindle-shape clones and IT15 cells yielding a majority of epithelioid clones. Epithelioid SMCs, cultured as whole or clonal cell populations, show less-differentiated cytoskeletal features (eg,
-SM
actin, SM myosin, and desmin expression), are able to grow in the
absence of serum, and exhibit higher migratory activity compared with
spindle-shape cells.77 78 Taken together, these findings
suggest that intimal thickening develops essentially from a
subpopulation of medial SMCs exhibiting epithelioid features in
vitro.
In an attempt to identify proteins differentially expressed between
different SMC phenotypes, we have observed that CRBP expression
is restricted to rat aortic SMCs cultured from IT15 cells displaying an
epithelioid phenotype and to epithelioid clones derived from
either the normal media or IT15 cells.2 79 Thus, CRBP
expression can be used as a marker of epithelioid cells in vitro.
Moreover, CRBP is transiently expressed by a subset of SMCs during
neointima formation. CRBP-positive cells proliferate at
early stages and disappear, allegedly through apoptosis, at
later stages of neointimal evolution,2
suggesting that a modulation of the retinoid content may be required
for both processes. CRBP upregulation is a direct transcriptional
effect of RA, mediated through binding of the RAR-–RXR-
heterodimer to the RARE of the CRBP promoter.80 In SMCs,
the pattern of expression of the 3 RAR and RXR genes has been
studied.5 Five of the 6 receptors are expressed in
rat SMCs in vitro, but in vivo, only RXR- is undetectable. The
presence of these receptors indicates that SMCs can respond to RA.
RA modulates various SMC features. It has been reported that RA either
increases81 or decreases2 5 82 SMC
proliferation. This paradoxical effect has recently been clarified by
Chen and Gardner83 : RA stimulates quiescent SMCs by
increasing expression of cyclin D1, which is involved in cell entry
into the G1 phase, whereas serum-stimulated cells are growth inhibited
through a decrease in extracellular signal–regulated protein kinase
activity. This property seems to be independent of SMC
phenotype, because serum-stimulated epithelioid and
spindle-shape SMCs are growth inhibited.28 The role of RA
in SMC migration in vitro remains unclear. The plasminogen
activator (PA) system and the matrix metalloproteinases
(MMPs) are both involved in extracellular matrix (ECM) degradation,
which is believed to mediate SMC migration. RA has been shown to reduce
SMC migration, possibly by decreasing collagenase and
stromelysin transcription, 2 MMPs induced by mechanical
injury.84 However, we have observed that RA increases
migration of both medial and IT15 SMCs, probably by stimulating
tissue-type plasminogen activator (tPA)
activity.28 tPA is the main PA involved in the proteolytic
activities of SMCs in vitro, and the higher proteolytic activity of
IT15 cells is mainly due to increased expression of tPA.29
Thus, the opposite effects of RA on SMC migration in vitro are likely
due to its differential action on the PA system and MMPs (see the
section below on RA and SMC Gene Expression). In addition to SMC
proliferation and migration, RA may influence SMC differentiation,
because -SM actin expression can be enhanced or
reduced,10 28 and SMC phenotype, because RA
induces the transition from the epithelioid shape to the spindle
one.2
The action of RA in vivo is less controversial. In the rat carotid injury model, RA decreases neointimal cellularity and ECM deposition, leading to a one-third increase in lumen diameter and area.28 85 86 RA also induces favorable remodeling of the injured artery.85 87 Medial area and cell number are unaffected, suggesting, among several possibilities, that in vivo RA specifically influences the SMCs prone to migrate, proliferate, and give rise to the neointima. As discussed above, this RA responsiveness may be correlated with a particular phenotypic and/or embryological origin.
Because different SMC phenotypes are engaged in different
genetic programs, it is of interest to investigate possible
differential expression of the 5 receptors or of the isoforms
corresponding to a given RAR subtype. To identify which RAR may have a
differential effect on distinct SMC phenotypes, we tested RA
agonists specific for each receptor. Among them, only RAR- agonists
were able to inhibit SMC proliferation in vitro and to reduce
intimal thickening formation in vivo.28 Thus, RA
may specifically influence the SMC phenotype responsible for
formation of the neointima through an RAR-–dependent
signaling pathway. It has recently been reported that RAR- agonists
inhibit in vitro SMC proliferation as well.82 These
results suggest that RA may be potentially useful in regulating SMC
differentiation, migration, and proliferation in vascular diseases
involving neointima formation.
It has been suggested that in some situations, the vascular healing
process may involve adventitial fibroblasts in producing
arterial remodeling and/or neointima
formation.88 These fibroblasts modulate into
myofibroblasts expressing -SM actin and producing ECM components
under transforming growth factor-ß (TGF-ß)
stimulation.89 90 We have observed that after induction of
an open wound in the back skin of the rat, myofibroblasts start to
express CRBP during the proliferation phase; CRBP expression persists
until myofibroblasts disappear through
apoptosis.91 These observations are compatible
with the possibility that CRBP expression and RA modulation are common
features of repair processes. Our results suggest that RA may be
potentially useful in regulating SMC differentiation, migration, and
proliferation in vascular diseases involving neointima
formation.
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RA and SMC Gene Expression |
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TopIntroductionRA and SMC LineageRA and SMC Biological...RA and SMC Gene...Conclusions and PerspectivesReferences |
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RA influences the expression of many genes, including those associated with cell growth and differentiation.43 It may activate the transcription of target genes or repress other genes by antagonizing the function of the activator protein-1 (AP-1) transcription factor.92 AP-1 is a heterodimer of c-fos and c-jun that binds to AP-1 consensus sequences and activates genes related to cell proliferation, migration, apoptosis, and ECM production.93 These 4 processes have been shown to play key roles in the progression of atherosclerosis and restenosis.94 95 An impressive number of genes are positively or negatively regulated by RA (see the Table
). Most
of them are in some way involved in the development of atherosclerotic
lesions or in the formation of the arterial
neointima. Thus, c-fos and c-jun are
rapidly induced after arterial injury, leading to the
formation of AP-1 and to the activation of AP-1–regulated
genes,33 such as fibroblast growth factor-2,
TGF-ß1, c-myc, endothelin-1, stromelysin,
collagenase, or the precursor of the MMP-1,
pro–MMP-1.40 96 97 RA can inhibit the expression of
some of these genes, such as those for collagenase,
stromelysin, and pro–MMP-1.32 40 98 The RA-induced
inhibition of MMPs is generally accompanied by an RA-mediated
activation of genes encoding ECM components, such as fibronectin,
laminin, and collagen type IV.99 100 Thus, RA allegedly
modifies the SMC genetic program to favor the formation of ECM, which
may in turn decrease cell migration and maintain cell
differentiation.101 102 In relation to
cardiovascular diseases, the action of RA as a negative
regulator of AP-1–responsive genes may be considered beneficial. On
the other hand, arterial injury results in an increase of
platelet-derived growth factor (PDGF), PDGF receptors, and
TGF-ß194 103 that are responsible for the induction of
SMC migration and proliferation and that are also potential target
genes for RA.104 105 Moreover, some of the actions of RA
are considered to be mediated or potentiated by induction of TGF-ß1,
and cross-talk between their signal transduction pathways is well
established.106 107 Thus, it appears that RA is also
capable of enhancing the effects of atherogenic growth factors. These
observations underline the complexity of the RA influence on SMCs and
support the notion that the action of RA on SMC behavior, and probably
on vascular diseases, largely depends on local environmental changes
and on the pattern of genes expressed at a given time. |
Conclusions and Perspectives |
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TopIntroductionRA and SMC LineageRA and SMC Biological...RA and SMC Gene...Conclusions and PerspectivesReferences |
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Although it is well accepted that RA plays an important role in vascular development, the multifaceted activity of RA in arterial SMCs of adult animals is presently an emerging, though rapidly developing, topic. It is now well established that RA influences SMC replication and motility, and, through its pleiotropic action, RA may affect other processes involved in the pathogenesis of vascular diseases. Recent work points particularly to the possibility that RA affects SMC participation in such phenomena as restenosis and plaque formation.28 85 The findings that RA can exert distinct actions on epithelioid versus spindle SMC phenotypes in culture and can reduce experimental intimal thickening in vivo are encouraging; however, further work is required to elucidate the mechanisms by which RA affects SMC function in vitro and in vivo. Nevertheless, one can confidently anticipate that the field of SMC modulation by RA in biological and pathological situation will develop importantly during the next several years.
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Acknowledgments |
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This study was supported in part by the Swiss National Science Foundation (Grant No. 31.50568-97). We thank Sabine Josseron for typing the manuscript.
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Footnotes |
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Göran Hansson kindly served as Guest Editor for this article.
Received November 3, 1999; accepted May 29, 2000.
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References |
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TopIntroductionRA and SMC LineageRA and SMC Biological...RA and SMC Gene...Conclusions and PerspectivesReferences |
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1. Blomhoff R. Transport and metabolism of vitamin A. Nutr Rev. 1994;52:S13–S23.[Medline] [Order article via Infotrieve]
2. Neuville P, Geinoz A, Benzonana G, Redard M, Gabbiani F, Ropraz P, Gabbiani G. Cellular retinol-binding protein-1 is expressed by distinct subsets of rat arterial smooth muscle cells in vitro and in vivo. Am J Pathol. 1997;150:509–521.[Abstract]
3.
Astrom A, Pettersson U, Chambon P, Voorhees JJ.
Retinoic acid induction of human cellular retinoic acid-binding
protein-II gene transcription is mediated by retinoic acid
receptor-retinoid X receptor heterodimers bound to one far upstream
retinoic acid-responsive element with 5-base pair spacing. J
Biol Chem. 1994;269:22334–22339.
4.
Dencker L, Annerwall E, Busch C, Eriksson U.
Localization of specific retinoid-binding sites and expression of
cellular retinoic-acid-binding protein (CRABP) in the early mouse
embryo. Development. 1990;110:343–353.
5.
Miano JM, Topouzis S, Majesky MW, Olson EN. Retinoid
receptor expression and all-trans retinoic acid–mediated
growth inhibition in vascular smooth muscle cells.
Circulation. 1996;93:1886–1895.
6.
Ricote M, Huang J, Fajas L, Li A, Welch J, Najib J,
Witztum JL, Auwerx J, Palinski W, Glass CK. Expression of the
peroxisome proliferator-activated receptor (PPAR)
in human atherosclerosis and regulation in
macrophages by colony stimulating factors and oxidized low
density lipoprotein. Proc Natl Acad Sci U S A. 1998;95:7614–7619.
7.
Marx N, Schonbeck U, Lazar MA, Libby P, Plutzky J.
Peroxisome proliferator-activated receptor
activators inhibit gene expression and migration in human
vascular smooth muscle cells. Circ Res. 1998;83:1097–1103.
8.
Staels B, Koenig W, Habib A, Merval R, Lebret M,
Torra IP, Delerive P, Fadel A, Chinetti G, Fruchart JC, Najib J,
Maclouf J, Tedgui A. Activation of human aortic smooth-muscle cells is
inhibited by PPAR but not by PPAR activators.
Nature. 1998;393:790–793.[Medline]
[Order article via Infotrieve]
9. Sadhu DN, Ramos K. Modulation by retinoic acid of spontaneous and benzo(a)pyrene-induced c-Ha-ras expression. Basic Life Sci. 1993;61:263–268.[Medline] [Order article via Infotrieve]
10.
Haller H, Lindschau C, Quass P, Distler A, Luft FC.
Differentiation of vascular smooth muscle cells and the regulation of
protein kinase C-. Circ Res. 1995;76:21–29.
11. McCarty MF. Up-regulation of intracellular signaling pathways may play a central pathogenic role in hypertension, atherogenesis, insulin resistance, and cancer promotion: the ‘PKC syndrome.’ Med Hypotheses. 1996;46:191–221.[Medline] [Order article via Infotrieve]
12.
Cohen PS, Letterio JJ, Gaetano C, Chan J, Matsumoto
K, Sporn MB, Thiele CJ. Induction of transforming growth
factor ß1 and its receptors during all-trans-retinoic acid (RA)
treatment of RA-responsive human neuroblastoma cell lines. Cancer
Res. 1995;55:2380–2386.
13.
Bobik A, Agrotis A, Kanellakis P, Dilley R,
Krushinsky A, Smirnov V, Tararak E, Condron M, Kostolias G. Distinct
patterns of transforming growth factor-ß isoform and receptor
expression in human atherosclerotic lesions: colocalization implicates
TGF-ß in fibrofatty lesion development. Circulation. 1999;99:2883–2891.
14.
Cippitelli M, Ye J, Viggiano V, Sica A, Ghosh P,
Gulino A, Santoni A, Young HA. Retinoic acid-induced transcriptional
modulation of the human interferon- promoter. J Biol
Chem. 1996;271:26783–26793.
15.
Vaddi K, Nicolini FA, Mehta P, Mehta JL. Increased
secretion of tumor necrosis factor- and interferon- by
mononuclear leukocytes in patients with ischemic heart disease:
relevance in superoxide anion generation. Circulation. 1994;90:694–699.
16. Hirokawa K, O’Shaughnessy KM, Ramrakha P, Wilkins MR. Inhibition of nitric oxide synthesis in vascular smooth muscle by retinoids. Br J Pharmacol. 1994;113:1448–1454.[Medline] [Order article via Infotrieve]
17.
Sirsjo A, Gidlof AC, Olsson A, Torma H, Ares M,
Kleinert H, Forstermann U, Hansson GK. Retinoic acid inhibits nitric
oxide synthase-2 expression through the retinoic acid receptor-.
Biochem Biophys Res Commun.. 2000;270:846–851.[Medline]
[Order article via Infotrieve]
18.
Afink GB, Nister M, Stassen BH, Joosten PH,
Rademakers PJ, Bongcam-Rudloff E, Van Zoelen EJ, Mosselman S. Molecular
cloning and functional characterization of the human
platelet-derived growth factor receptor gene promoter.
Oncogene. 1995;10:1667–1672.[Medline]
[Order article via Infotrieve]
19.
Krettek A, Fager G, Jernberg P, Ostergren-Lunden G,
Lustig F. Quantitation of platelet-derived growth factor receptors
in human arterial smooth muscle cells in vitro.
Arterioscler Thromb Vasc Biol. 1997;17:2395–2404.
20. Gudas LJ. Assays for expression of genes regulated by retinoic acid in murine teratocarcinoma cell lines. Methods Enzymol. 1990;190:131–140.[Medline] [Order article via Infotrieve]
21. Thyberg J, Hulgardh-Nilsson A. Fibronectin and the basement membrane components laminin and collagen type IV influence the phenotypic properties of subcultured rat aortic smooth muscle cells differently. Cell Tissue Res. 1994;276:262–271.
22. Robert L, Robert AM, Jacotot B. Elastin-elastase-atherosclerosis revisited. Atherosclerosis.. 1998;140:281–295.[Medline] [Order article via Infotrieve]
23.
Hayashi A, Suzuki T, Tajima S. Modulations of elastin
expression and cell proliferation by retinoids in cultured vascular
smooth muscle cells. J Biochem (Tokyo). 1995;117:132–136.
24.
Yeh HI, Lupu F, Dupont E, Severs NJ. Upregulation of
connexin43 gap junctions between smooth muscle cells after balloon
catheter injury in the rat carotid artery. Arterioscler Thromb
Vasc Biol. 1997;17:3174–3184.
25. Clairmont A, Sies H. Evidence for a posttranscriptional effect of retinoic acid on connexin43 gene expression via the 3'-untranslated region. FEBS Lett. 1997;419:268–270.[Medline] [Order article via Infotrieve]
26.
Braun M, Pietsch P, Schror K, Baumann G, Felix SB.
Cellular adhesion molecules on vascular smooth muscle cells.
Cardiovasc Res. 1999;41:395–401.
27. Stratowa C, Audette M. Transcriptional regulation of the human intercellular adhesion molecule-1 gene: a short overview. Immunobiology. 1995;193:293–304.[Medline] [Order article via Infotrieve]
28.
Neuville P, Yan Z, Gidlof A, Pepper MS, Hansson GK,
Gabbiani G, Sirsjo A. Retinoic acid regulates arterial
smooth muscle cell proliferation and phenotypic features in vivo and in
vitro through an RAR-dependent signaling pathway.
Arterioscler Thromb Vasc Biol. 1999;19:1430–1436.
29.
Bochaton-Piallat ML, Gabbiani G, Pepper MS.
Plasminogen activator expression in rat
arterial smooth muscle cells depends on their
phenotype and is modulated by cytokines. Circ
Res. 1998;82:1086–1093.
30. Golja AM, Rodino W, Panetta TF. Insight into atherosclerosis: a review of c-myc and the vascular smooth muscle cell. Cell Mol Biol Res. 1995;41:487–499.[Medline] [Order article via Infotrieve]
31.
Griep AE, DeLuca HF. Decreased c-myc expression is an
early event in retinoic acid-induced differentiation of F9
teratocarcinoma cells. Proc Natl Acad Sci U S A. 1986;83:5539–5543.
32. Nicholson RC, Mader S, Nagpal S, Leid M, Rochette-Egly C, Chambon P. Negative regulation of the rat stromelysin gene promoter by retinoic acid is mediated by an AP1 binding site. EMBO J. 1990;9:4443–4454.[Medline] [Order article via Infotrieve]
33.
Miano JM, Vlasic N, Tota RR, Stemerman MB. Smooth
muscle cell immediate-early gene and growth factor activation follows
vascular injury: a putative in vivo mechanism for autocrine growth.
Arterioscler Thromb. 1993;13:211–219.
34. Sirtori CR, Calabresi L, Franceschini G. Recombinant apolipoproteins for the treatment of vascular diseases. Atherosclerosis. 1999;142:29–40.[Medline] [Order article via Infotrieve]
35. Hargrove GM, Junco A, Wong NC. Hormonal regulation of apolipoprotein AI. J Mol Endocrinol. 1999;22:103–111.[Abstract]
36. Varani J, Nickoloff BJ, Dixit VM, Mitra RS, Voorhees JJ. All-trans retinoic acid stimulates growth of adult human keratinocytes cultured in growth factor-deficient medium, inhibits production of thrombospondin and fibronectin, and reduces adhesion. J Invest Dermatol. 1989;93:449–454.[Medline] [Order article via Infotrieve]
37. Riessen R, Kearney M, Lawler J, Isner JM. Immunolocalization of thrombospondin-1 in human atherosclerotic and restenotic arteries. Am Heart J. 1998;135:357–364.[Medline] [Order article via Infotrieve]
38. Gille J, Paxton LLL, Lawley TJ, Caughman SW, Swerlick RA. Retinoic acid inhibits the regulated expression of vascular cell adhesion molecule-1 by cultured dermal microvascular endothelial cells. J Clin Invest. 1997;99:492–500.[Medline] [Order article via Infotrieve]
39.
Barstad RM, Hamers MJ, Stephens RW, Sakariassen KS.
Retinoic acid reduces induction of monocyte tissue factor and tissue
factor/factor VIIa-dependent arterial thrombus formation.
Blood. 1995;86:212–218.
40. Kato S, Sasaguri Y, Morimatsu M. Down-regulation in the production of matrix metalloproteinase 1 by human aortic intimal smooth muscle cells. Biochem Mol Biol Int. 1993;31:239–248.[Medline] [Order article via Infotrieve]
41. Pan L, Eckhoff C, Brinckerhoff CE. Suppression of collagenase gene expression by all-trans and 9-cis retinoic acid is ligand dependent and requires both RARs and RXRs. J Cell Biochem. 1995;57:575–589.[Medline] [Order article via Infotrieve]
42. Chytil F, Riaz-ul-Haq. Vitamin A mediated gene expression. Crit Rev Eukaryot Gene Expr. 1990;1:61–73.[Medline] [Order article via Infotrieve]
43.
Giguere V. Retinoic acid receptors and cellular
retinoid binding proteins: complex interplay in retinoid signaling.
Endocr Rev. 1994;15:61–79.
44. Pemrick SM, Lucas DA, Grippo JF. The retinoid receptors. Leukemia. 1994;8:1797–1806.[Medline] [Order article via Infotrieve]
45. Kastner P, Mark M, Chambon P. Nonsteroid nuclear receptors: what are genetic studies telling us about their role in real life? Cell. 1995;83:859–869.[Medline] [Order article via Infotrieve]
46.
Boerman MH, Napoli JL. Cellular retinol-binding
protein-supported retinoic acid synthesis: relative roles of microsomes
and cytosol. J Biol Chem. 1996;271:5610–5616.
47. Napoli JL, Posch KP, Fiorella PD, Boerman MH. Physiological occurrence, biosynthesis and metabolism of retinoic acid: evidence for roles of cellular retinol-binding protein (CRBP) and cellular retinoic acid-binding protein (CRABP) in the pathway of retinoic acid homeostasis. Biomed Pharmacother. 1991;45:131–143.[Medline] [Order article via Infotrieve]
48. Kochhar DM. Limb development in mouse embryos, I: analysis of teratogenic effects of retinoic acid. Teratology. 1973;7:289–298.
49. Morriss-Kay G. Retinoic acid and development. Pathobiology. 1992;60:264–270.[Medline] [Order article via Infotrieve]
50. Taylor IM. The effect of retinoic acid on the developing hamster heart: an ultrastructural and morphological study. In: Persaud TVN, ed. Advances in the Study of Birth Defects III. Lancaster, Pa: Lancaster Press; 1979:119–134.
51. Heine UI, Roberts AB, Munoz EF, Roche NS, Sporn MB. Effects of retinoid deficiency on the development of the heart and vascular system of the quail embryo. Virchows Arch B Cell Pathol Incl Mol Pathol. 1985;50:135–152.[Medline] [Order article via Infotrieve]
52. Hart RC, McCue PA, Ragland WL, Winn KJ, Unger ER. Avian model for 13-cis-retinoic acid embryopathy: demonstration of neural crest related defects. Teratology. 1990;41:463–472.[Medline] [Order article via Infotrieve]
53.
Kirby ML, Waldo KL. Role of neural crest in
congenital heart disease. Circulation. 1990;82:332–340.
54. Waldo KL, Kirby ML. Cardiac neural crest contribution to the pulmonary artery and sixth aortic arch artery complex in chick embryos aged 6 to 18 days. Anat Rec. 1993;237:385–399.[Medline] [Order article via Infotrieve]
55. Le Lievre CS, Le Douarin NM. Mesenchymal derivatives of the neural crest: analysis of chimaeric quail and chick embryos. J Embryol Exp Morphol. 1975;34:125–154.[Medline] [Order article via Infotrieve]
56. Topouzis S, Majesky MW. Smooth muscle lineage diversity in the chick embryo: two types of aortic smooth muscle cell differ in growth and receptor-mediated transcriptional responses to transforming growth factor-ß. Dev Biol. 1996;178:430–445.
57. Ito K, Morita T. Role of retinoic acid in mouse neural crest cell development in vitro. Dev Dyn. 1995;204:211–218.[Medline] [Order article via Infotrieve]
58. Smith SM. Retinoic acid receptor isoform ß2 is an early marker for alimentary tract and central nervous system positional specification in the chicken. Dev Dyn. 1994;200:14–25.[Medline] [Order article via Infotrieve]
59. Maden M, Hunt P, Eriksson U, Kuroiwa A, Krumlauf R, Summerbell D. Retinoic acid-binding protein, rhombomeres and the neural crest. Development. 1991;111:35–43.[Abstract]
60.
Slomp J, Gittenberger-de Groot AC, Glukhova MA, van
Munsteren JC, Kockx MM, Schwartz SM, Koteliansky VE. Differentiation,
dedifferentiation, and apoptosis of smooth muscle cells during
the development of the human ductus arteriosus. Arterioscler
Thromb Vasc Biol. 1997;17:1003–1009.
61.
Kim HS, Aikawa M, Kimura K, Kuro-o M, Nakahara K,
Suzuki T, Katoh H, Okamoto E, Yazaki Y, Nagai R. Ductus arteriosus:
advanced differentiation of smooth muscle cells demonstrated by myosin
heavy chain isoform expression in rabbits. Circulation. 1993;88:1804–1810.
62.
Colbert MC, Kirby ML, Robbins J.
Endogenous retinoic acid signaling colocalizes with
advanced expression of the adult smooth muscle myosin heavy chain
isoform during development of the ductus arteriosus. Circ
Res. 1996;78:790–798.
63. Edwards MK, McBurney MW. The concentration of retinoic acid determines the differentiated cell types formed by a teratocarcinoma cell line. Dev Biol. 1983;98:187–191.[Medline] [Order article via Infotrieve]
64. Rudnicki MA, Sawtell NM, Reuhl KR, Berg R, Craig JC, Jardine K, Lessard JL, McBurney MW. Smooth muscle actin expression during P19 embryonal carcinoma differentiation in cell culture. J Cell Physiol. 1990;142:89–98.[Medline] [Order article via Infotrieve]
65.
Wei LN, Blaner WS, Goodman DS, Nguyen-Huu MC.
Regulation of the cellular retinoid-binding proteins and their
messenger ribonucleic acids during P19 embryonal carcinoma cell
differentiation induced by retinoic acid. Mol Endocrinol. 1989;3:454–463.
66.
Eriksson U, Hansson E, Nilsson M, Jonsson KH,
Sundelin J, Peterson PA. Increased levels of several retinoid binding
proteins resulting from retinoic acid-induced differentiation of F9
cells. Cancer Res. 1986;46:717–722.
67.
Blank RS, Swartz EA, Thompson MM, Olson EN, Owens GK.
A retinoic acid-induced clonal cell line derived from multipotential
P19 embryonal carcinoma cells expresses smooth muscle characteristics.
Circ Res. 1995;76:742–749.
68.
Pratt MA, Kralova J, McBurney MW. A dominant negative
mutation of the retinoic acid receptor gene in a retinoic
acid-nonresponsive embryonal carcinoma cell. Mol Cell Biol. 1990;10:6445–6453.
69.
Costa SL, McBurney MW. Dominant negative mutant of
retinoic acid receptor inhibits retinoic acid-induced P19 cell
differentiation by binding to DNA. Exp Cell Res. 1996;225:35–43.[Medline]
[Order article via Infotrieve]
70. Campbell G, Campbell J. The phenotypes of smooth muscle expressed in human atheroma. Ann N Y Acad Sci. 1990;598:143–158.[Medline] [Order article via Infotrieve]
71. Thyberg J, Blomgren K, Hedin U, Dryjski M. Phenotypic modulation of smooth muscle cells during the formation of neointimal thickenings in the rat carotid artery after balloon injury: an electron-microscopic and stereological study. Cell Tissue Res. 1995;281:421–433.[Medline] [Order article via Infotrieve]
72. Villaschi S, Nicosia RF, Smith MR. Isolation of a morphologically and functionally distinct smooth muscle cell type from the intimal aspect of the normal rat aorta: evidence for smooth muscle cell heterogeneity. In Vitro Cell Dev Biol Anim. 1994;30A:589–595.
73.
Frid MG, Aldashev AA, Dempsey EC, Stenmark KR. Smooth
muscle cells isolated from discrete compartments of the mature vascular
media exhibit unique phenotypes and distinct growth
capabilities. Circ Res. 1997;81:940–952.
74.
Majesky MW, Giachelli CM, Reidy MA, Schwartz SM. Rat
carotid neointimal smooth muscle cells reexpress a
developmentally regulated mRNA phenotype during repair of
arterial injury. Circ Res. 1992;71:759–768.
75.
Walker LN, Bowen-Pope DF, Ross R, Reidy MA.
Production of platelet-derived growth factor-like molecules
by cultured arterial smooth muscle cells accompanies
proliferation after arterial injury. Proc Natl Acad
Sci U S A. 1986;83:7311–7315.
76.
Orlandi A, Ehrlich HP, Ropraz P, Spagnoli LG,
Gabbiani G. Rat aortic smooth muscle cells isolated from different
layers and at different times after endothelial
denudation show distinct biological features in vitro.
Arterioscler Thromb Vasc Biol. 1994;14:982–989.
77. Lemire JM, Covin CW, White S, Giachelli CM, Schwartz SM. Characterization of cloned aortic smooth muscle cells from young rats. Am J Pathol. 1994;144:1068–1081.[Abstract]
78.
Bochaton-Piallat ML, Ropraz P, Gabbiani F, Gabbiani
G. Phenotypic heterogeneity of rat arterial
smooth muscle cell clones: implications for the development of
experimental intimal thickening. Arterioscler Thromb Vasc
Biol. 1996;16:815–820.
79. Cremona O, Muda M, Appel RD, Frutiger S, Hughes GJ, Hochstrasser DF, Geinoz A, Gabbiani G. Differential protein expression in aortic smooth muscle cells cultured from newborn and aged rats. Exp Cell Res. 1995;217:280–287.[Medline] [Order article via Infotrieve]
80. Husmann M, Hoffmann B, Stump DG, Chytil F, Pfahl M. A retinoic acid response element from the rat CRBPI promoter is activated by an RAR/RXR heterodimer. Biochem Biophys Res Commun. 1992;187:1558–1564.[Medline] [Order article via Infotrieve]
81. Peclo MM, Printseva O. Retinoic acid enhances the proliferation of smooth muscle cells. Experientia. 1987;43:196–198.[Medline] [Order article via Infotrieve]
82.
Pakala R, Benedict CR. RAR- agonists inhibit
proliferation of vascular smooth muscle cells. J Cardiovasc
Pharmacol.. 2000;35:302–308.[Medline]
[Order article via Infotrieve]
83. Chen SC, Gardner DG. Retinoic acid uses divergent mechanisms to activate or suppress mitogenesis in rat aortic smooth muscle cells. J Clin Invest. 1998;102:653–662.[Medline] [Order article via Infotrieve]
84. James TW, Wagner R, White LA, Zwolak RM, Brinckerhoff CE. Induction of collagenase and stromelysin gene expression by mechanical injury in a vascular smooth muscle-derived cell line. J Cell Physiol. 1993;157:426–437.[Medline] [Order article via Infotrieve]
85.
Miano JM, Kelly LA, Artacho CA, Nuckolls TA,
Piantedosi R, Blaner WS. All-trans-retinoic acid reduces
neointimal formation and promotes favorable geometric
remodeling of the rat carotid artery after balloon withdrawal injury.
Circulation. 1998;98:1219–1227.
86. DeRose JJ Jr, Madigan J, Umana JP, Prystowsky JH, Nowygrod R, Oz MC, Todd GJ. Retinoic acid suppresses intimal hyperplasia and prevents vessel remodeling following arterial injury. Cardiovasc Surg. 1999;7:633–639.[Medline] [Order article via Infotrieve]
87.
Wiegman PJ, Barry WL, McPherson JA, McNamara CA,
Gimple LW, Sanders JM, Bishop GG, Powers ER, Ragosta M, Owens GK,
Sarembock IJ. All-trans-retinoic acid limits
restenosis after balloon angioplasty in the focally
atherosclerotic rabbit: a favorable effect on vessel remodeling.
Arterioscler Thromb Vasc Biol.. 2000;20:89–95.
88.
Zalewski A, Shi Y. Vascular myofibroblasts: lessons
from coronary repair and remodeling. Arterioscler Thromb
Vasc Biol. 1997;17:417–422.
89.
Shi Y, O’Brien JE, Fard A, Zalewski A. Transforming
growth factor-ß expression and myofibroblast formation during
arterial repair. Arterioscler Thromb Vasc Biol. 1996;16:1298–1305.
90.
Shi Y, O’Brien JE Jr, Ala-Kokko L, Chung W, Mannion
JD, Zalewski A. Origin of extracellular matrix synthesis during
coronary repair. Circulation. 1997;95:997–1006.
91. Xu G, Redard M, Gabbiani G, Neuville P. Cellular retinol-binding protein-1 is transiently expressed in granulation tissue fibroblasts and differentially expressed in fibroblasts cultured from different organs. Am J Pathol. 1997;151:1741–1749.[Abstract]
92.
Schule R, Rangarajan P, Yang N, Kliewer S, Ransone
LJ, Bolado J, Verma IM, Evans RM. Retinoic acid is a negative regulator
of AP-1-responsive genes. Proc Natl Acad Sci U S A. 1991;88:6092–6096.
93. Karin M, Liu Z, Zandi E. AP-1 function and regulation. Curr Opin Cell Biol. 1997;9:240–246.[Medline] [Order article via Infotrieve]
94.
Schwartz SM, deBlois D, O’Brien ER. The intima: soil
for atherosclerosis and restenosis. Circ
Res. 1995;77:445–465.
95.
Kockx MM. Apoptosis in the atherosclerotic
plaque: quantitative and qualitative aspects. Arterioscler Thromb
Vasc Biol. 1998;18:1519–1522.
96. Griendling KK, Alexander RW. Endothelial control of the cardiovascular system: recent advances. FASEB J. 1996;10:283–292.[Abstract]
97. Bennett M, Anglin S, McEwan J, Jagoe R, Newby A, Evan G. Inhibition of vascular smooth muscle cell proliferation in vitro and in vivo by C-myc antisense oligodeoxynucleotides. J Clin Invest. 1994;93:820–828.
98.
Lafyatis R, Kim SJ, Angel P, Roberts AB, Sporn MB,
Karin M, Wilder RL. Interleukin-1 stimulates and all-trans-retinoic
acid inhibits collagenase gene expression through its 5'
activator protein-1-binding site. Mol
Endocrinol. 1990;4:973–980.
99. Varani J, Mitra RS, Gibbs D, Phan SH, Dixit VM, Mitra R Jr, Wang T, Siebert KJ, Nickoloff BJ, Voorhees JJ. All-trans retinoic acid stimulates growth and extracellular matrix production in growth-inhibited cultured human skin fibroblasts. J Invest Dermatol. 1990;94:717–723.[Medline] [Order article via Infotrieve]
100. Wang SY, LaRosa GJ, Gudas LJ. Molecular cloning of gene sequences transcriptionally regulated by retinoic acid and dibutyryl cyclic AMP in cultured mouse teratocarcinoma cells. Dev Biol. 1985;107:75–86.[Medline] [Order article via Infotrieve]
101.
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.
102. Hayward IP, Bridle KR, Campbell GR, Underwood PA, Campbell JH. Effect of extracellular matrix proteins on vascular smooth muscle cell phenotype. Cell Biol Int. 1995;19:839–846.[Medline] [Order article via Infotrieve]
103. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1990;362:801–809.
104. Mercola M, Wang CY, Kelly J, Brownlee C, Jackson-Grusby L, Stiles C, Bowen-Pope D. Selective expression of PDGF A and its receptor during early mouse embryogenesis. Dev Biol. 1990;138:114–122.[Medline] [Order article via Infotrieve]
105.
Falk LA, De Benedetti F, Lohrey N,
Birchenall-Roberts MC, Ellingsworth LW, Faltynek CR, Ruscetti FW.
Induction of transforming growth factor-ß 1 (TGF-ß 1),
receptor expression and TGF-ß 1 protein production in
retinoic acid-treated HL-60 cells: possible TGF-ß 1-mediated
autocrine inhibition. Blood. 1991;77:1248–1255.
106. Roberts AB, Sporn MB. Mechanistic interrelationships between two superfamilies: the steroid/retinoid receptors and transforming growth factor-ß. Cancer Surv. 1992;14:205–220.[Medline] [Order article via Infotrieve]
107. Nugent P, Greene RM. Interactions between the transforming growth factor ß (TGFß) and retinoic acid signal transduction pathways in murine embryonic palatal cells. Differentiation. 1994;58:149–155.[Medline] [Order article via Infotrieve]
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