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(Hypertension. 1995;25:464-473.)
© 1995 American Heart Association, Inc.
Articles |
Regional Heterogeneity of Arterial Structural Changes
From the Departments of Pathology (M.J.A.P.D.) and Pharmacology (J.G.R. De M.), Cardiovascular Research Institute Maastricht, University of Limburg, Maastricht, Netherlands.
Correspondence to Dr J.G.R. De Mey, Department of Pharmacology, University of Limburg, PO Box 616, 6200 MD Maastricht, Netherlands.
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Abstract |
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 Top Abstract IntroductionVascular Heterogeneity in...Heterogeneity of Vascular Growth...What Causes Heterogeneity?Summary and PerspectiveReferences |
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Abstract Arterial structural changes in experimental models of hypertension and restenosis differ between vessel types and within vessels. Inspired by the diversity of short-term functional responses to vasoactive agents, hypotheses are presented with respect to the heterogeneity of structural alterations. Considered are the multifactorial nature of smooth muscle cell growth control and the possibility that vascular smooth muscle is not homogeneous but composed of different smooth muscle cell populations. These hypotheses may help explain the origin of both intervascular and intravascular heterogeneity of vascular structural responses.
Key Words: muscle, smooth • endothelium • nerves • angiotensin II • arteries
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Introduction |
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TopAbstractIntroductionVascular Heterogeneity in...Heterogeneity of Vascular Growth...What Causes Heterogeneity?Summary and PerspectiveReferences |
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A great deal of our current knowledge of the vascular wall has been based on studies of vascular cells in culture and on the contractile reactivity of isolated vessel strips. Often, articles trying to explain in vivo phenomena will discuss these in vitro data in an indiscriminate fashion. However, there are indications that smooth muscle cells (SMCs) may be heterogeneous and exposed to different combinations of stimuli and inhibitors at different locations along the vascular system. In this article we illustrate the various presentations and possible origins of heterogeneity of structural vascular responses and the role of angiotensin II (Ang II), nerves, and the endothelium. We will consider both differences between vessel segments and the diversity of vascular SMCs.
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Vascular Heterogeneity in General |
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TopAbstractIntroductionVascular Heterogeneity in...Heterogeneity of Vascular Growth...What Causes Heterogeneity?Summary and PerspectiveReferences |
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Short-term pharmacological observations indicate that several types and levels of vascular heterogeneity may be distinguished (Table 1). Documented most extensively are differences between vessel types, ie, intervascular heterogeneity. These differences may be quantitative or qualitative. They may be observed between the same type of vessel of different species, between vessels of different vascular beds in the same species, and between branches of the same vascular bed.1 2 Not all intervascular heterogeneity is due to diversity of innervation, the endothelium, and other intravascular sources of bioactive agents but may reside in regional differences of the vascular smooth muscle. Thus, vascular smooth muscle heterogeneity does not coincide with vascular heterogeneity. Furthermore, recent observations suggest that the SMCs that make up the media of a given vascular segment are not necessarily homogeneous3 4 (see below). This intravascular heterogeneity of SMCs has largely been overlooked by functional vascular studies. From a mechanistic point of view, it may also be helpful to distinguish between stable and reversible forms of vascular heterogeneity to discriminate between rather short-term environmental influences on vascular properties (such as receptor downregulation and tolerance of biochemical pathways) and poorly reversible decisions made at the molecular level in the cell types involved (such as phenotypic and genotypic differences). Possibly related to this aspect are different responses in vessels of fetal, young, adult, and old animals (heterogeneity in time).
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Heterogeneity of Vascular Growth Responses |
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TopAbstractIntroductionVascular Heterogeneity in...Heterogeneity of Vascular Growth...What Causes Heterogeneity?Summary and PerspectiveReferences |
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Structural changes in the vasculature play an important role in cardiovascular diseases.5 6 In general, two major types of structural changes can be distinguished: (1) alterations in the branching, length, and number of microvessels and (2) changes in the thickness and organization of the vascular wall (Fig 1). This review will consider only the latter radial changes.
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Growth and proliferation of SMCs participate in medial hypertrophy in hypertension5 7 8 and in intimal thickening in atherosclerosis9 10 and restenosis after angioplasty.11 In recent years, SMC growth control has been the subject of extensive investigations in a limited number of experimental models. Widely used are culture of isolated aortic SMCs12 and structural responses of the aorta and carotid arteries to hypertension13 or balloon catheter injury.14 These models have helped make it increasingly clear that many factors are involved in SMC growth control. Growth factors, cytokines, and extracellular matrix components have received much attention.5 15 16 17 18 19 However, mechanical factors, neurotransmitters, hormones, and autacoids15 16 20 also participate.16 21 22 23 Multifactorial control of SMC growth provides ample opportunity for heterogeneous structural changes in blood vessels. Also in this case different types and levels of heterogeneity can be distinguished. It may be important to note that besides true differences between experimental models, differences between experimental protocols and the normotensive controls used may also account for some of the divergent findings.
Differences Between Blood Vessels or Intervascular
Heterogeneity
Cell Culture
Enzymes and explants have been used to isolate SMCs (cells
expressing smooth muscle 
-actin when maintained at high density)
from various blood vessels.12 SMCs isolated from large
arteries of adult mammals lack contact inhibition and proliferate
rapidly in a serum-dependent manner. For several species, the
population doubling time of large-artery SMCs ranges between 20 and 30
hours. Yet microvascular SMCs obtained from rat mesentery need 3 to 6
days to replicate under identical conditions.24
Furthermore, cultured aortic SMCs of newborn rats differ from those of
adult rats in several respects. They show platelet-derived growth
factor (PDGF)–independent growth and constitutively secrete PDGF,
express specific genes, and have a distinct epithelial morphology.
Cultures of medial SMCs from adult animals show none of these
properties and have the usual hill-and-valley
morphology.25 26 These differences and the difference
between adult microvascular and adult large-artery SMCs persist after
several passages in vitro, suggesting stable
heterogeneity.24 25 This is also the case for the
different growth characteristics, differences in growth-related signal
transduction pathways, and differences in the production of
growth-affecting mediators and extracellular matrix (ECM) components
observed between aortic SMCs of spontaneously hypertensive rats (SHR)
and normotensive Wistar-Kyoto rats (WKY).27 28 29 30
Organ Culture
Exposure of isolated arterial segments of humans,31
pigs,32 rabbits,33 34 and
rats24 35 to serum or growth factors stimulates DNA
synthesis in a variable fraction of the SMCs that populate the intact
media. For instance, in rat arteries we observed a 10-fold difference
between vessels of different anatomic origin with respect to the
fraction of SMCs that could be stimulated to synthesize DNA in
vitro.24 The differences in DNA synthesis between the
vessel types occurred despite identical proliferation rates of isolated
SMCs put into cell culture.
Arterial Injury
Retraction of an inflated balloon through the lumen of a blood
vessel removes the endothelium and damages the media.36
This ultimately gives rise to extensive SMC proliferation in the
intima. This structural response to injury differs among vessel types
and species (Table 2). For instance, in the rat carotid
artery, neointima formation is circular, whereas it is
largely restricted to the ventral surface in the rat thoracic
aorta.41 In addition, the extent of neointima
formation, defined as the ratio of intima to media mass, varies among
vessel types and species (Table 2).
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Hypertension
The type of arterial wall mass change in hypertension differs
along the arterial tree. Regional comparative studies have been
performed most extensively in SHR (Table 3). The
predominant alteration of large arteries in established genetic
hypertension consists of medial SMC hypertrophy and
hyperploidy.13 18 However, small resistance-sized arteries
show hyperplastic changes1 8 46 49 51 52 53 without an
increased incidence of SMC polyploidy.8 42 54 The wall
mass of arterioles, on the other hand, may be normal in
SHR47 55 56 57 and the number of capillaries
reduced.58 59 60 Hyperplasia is not a general finding in
resistance arteries; it was found in some but not all vascular beds of
SHR50 and was reported to be absent in renal hypertensive
rats,61 mouse Ren-2 renin transgenic
rats,62 and humans with essential
hypertension.63 In recent studies64 65 of DNA
synthesis in the arterial system of SHR, a marked heterogeneity was
observed. DNA synthesis was elevated in mesenteric resistance arteries
of SHR at 1 week of age but not at 2, 4, or 6 weeks of age. However, in
various large arteries of the same strain, intra-arterial DNA synthesis
was significantly elevated from 6 weeks of age but not at earlier
developmental stages.64 65 66
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Pharmacological Interventions
Many drugs can influence arterial structural responses. Effects of
antihypertensive agents on arterial wall hypertrophy and effects of
various classes of agents on neointima formation after
balloon injury have recently been reviewed.67 68 Here we
will limit ourselves to the diverse effects of interventions in the
renin-angiotensin and sympathetic nervous systems. Both systems
interact in the control of arterial structural responses because (1)
angiotensin-converting enzyme (ACE) inhibitors and sympathectomy are
equally effective in preventing arterial structural changes in
hypertension,67 (2) ACE inhibitors and
1-adrenoceptor antagonists are equally effective in
reducing neointima formation after balloon
injury,69 70 71 and (3) treatment with
1-adrenoceptor antagonists impairs the mitogenic
response of arteries to intravenously infused Ang II.72
Several types of ACE inhibitors have now been observed to reduce
neointima formation after balloon injury of rat and rabbit
arteries.69 73 74 In the pig and baboon, however, ACE
inhibition does not prevent neointimal thickening after
balloon injury.75 76 Furthermore, in humans no significant
effects of ACE inhibitor treatment could be detected with respect to
intima formation and the incidence of restenosis after
angioplasty.77 The role of Ang II in experimental
neointima formation in rat and rabbit seems to be primarily
mediated by Ang II type 1 (AT1) receptors because (1) in
the rat carotid artery, most (97%) angiotensin receptors have been
identified as AT1 by radioligand binding78 and
(2) in all but one study,79 long-term treatment with
losartan (DuP 753), an AT1 receptor antagonist, reduced
neointima formation40 73 80 as ACE inhibitors
do. ACE inhibitors are also effective in preventing the development of
high blood pressure and structural alterations in large and small
arteries of SHR.81 82 83 However, reversal of SMC hypertrophy
and hyperploidy in large arteries and reversal of SMC hyperplasia in
small resistance-sized arteries have not been uniformly obtained.
Also, interferences with the sympathetic nervous system alter vascular
structure. Infusion of an 1-adrenoceptor agonist
promotes DNA synthesis and hypertrophy in the aorta of young rats but
not in mesenteric resistance-sized vessels of these animals despite a
hypertrophic response at this site to systemic administration of Ang
II.84 On the other hand, injection of phenylephrine into
adult rats results in elevated expression of proto-oncogenes but not
DNA synthesis in the thoracic aorta.85 Effects of
sympathectomy have been investigated more extensively (Table 4). Neonatal immunosympathectomy with anti–nerve growth
factor and guanethidine prevents the development of high blood pressure
in SHR and stroke-prone SHR.43 45 The accompanying
structural changes differ among different artery types and between both
experimental models. In normotensive animals, structural vascular
effects of sympatholytic interventions differ between young and adult
animals (Table 4). In this instance, either no change or a reduction of
DNA synthesis has been observed in arteries of young
animals.45 86 87 88 In arteries of adults, on the other hand,
surgical denervation and 6-hydroxydopamine induce an
increase in SMC size and ultrastructural changes compatible with
increased synthetic activity.87 89 90 91 92 93 94 Thus, although
sympathetic nerves seem to exert a trophic action on vascular smooth
muscle during development, they may help stabilize the contractile
phenotype of the SMC in the adult. The cause of this heterogeneity in
time is not known but may involve, besides catecholamines, a role for
sympathetic cotransmitters such as ATP and neuropeptide Y and of
neurotransmitters released by peptidergic nerves. This hypothesis is
strengthened by observations that effects of ganglionectomy and
chemical denervation in the adult can be prevented by the
administration of an adenosine agonist94 but not by
exogenous norepinephrine.89 94 Furthermore, the structural
effects in the adult are not mimicked by guanethidine,89
which, unlike surgery or 6-hydroxydopamine, depletes
adrenergic nerve endings of catecholamines without affecting their ATP
and neuropeptide Y content and without affecting the integrity of the
sensory peptidergic nerves.
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Differences Within Vessels or Intravascular Heterogeneity
Vascular structural changes differ not only among different vessel
types; diverse growth-related responses have also been observed within
the wall of a given vascular segment.
Cell Culture
Observations in isolated cells support the existence of
intravascular heterogeneity only indirectly. Mitogenic actions of Ang
II differ among the SMCs isolated from different WKY, suggesting that
the tissues from which the cells were isolated were originally composed
of a mixture of Ang II–responsive and –nonresponsive
cells.95 Short-term pharmacological observations
strengthen this possibility because fewer rat aortic SMCs can be
stimulated to raise their cytoplasmic calcium concentrations by Ang II
than by norepinephrine or PDGF-BB.3 4 On the other hand,
although most isolated SMCs rapidly change their phenotype from a
contractile to a synthetic one5 12 96 97 98 99 when seeded at
low density in the presence of serum, SMC clones have recently been
derived from rat pulmonary artery100 that continue to
express smooth muscle -actin, a marker of contractile SMCs.
Selection of a subset of SMCs that are unable to change their phenotype
may explain this finding.
Organ Culture
Unlike isolated SMCs, only a small fraction of the medial cells
can be stimulated to synthesize DNA during culture of intact segments
or strips of human, pig, rabbit, or rat arteries.24 31 32 33 34 35
Furthermore, this response is transient. In rat arteries, endothelium
removal increases the amplitude of the stimulation but does not unmask
a mitogenic response in all medial cells.24 101
Arterial Injury
The structural response of arteries to balloon injury offers the
most convincing evidence of intravascular heterogeneity of a growth
response. The sequence of events that ultimately leads to
neointima formation can be described by a three-wave model.
Within 3 days after injury, significant DNA synthesis is initiated in
the otherwise quiescent media (first wave, Table 5).
This is followed by SMC migration to the intima (second wave). These
intimal SMCs proliferate extensively and form new layers of cells, the
neointima (third wave). The amplitude and time course of
the first wave resemble those observed during exposure of isolated
arteries to serum in vitro. Recent findings indicate that fibroblast
growth factor and heparin are involved in the first-wave response to
injury.102 103 104 However, the relevance of the first wave
for the ultimate structural response (neointima formation
and proliferation) is limited.111 The migration of a
limited number of SMCs to the intima,112 which may rely on
PDGF-BB and urokinase,105 107 plays a pivotal role.
Proliferation of neointimal SMCs has been suggested to
depend on transforming growth factor-ß1 and PDGF-AA108
rather than on fibroblast growth factor,113 which
plays a central role in medial SMC proliferation.102 103 104
In contrast, Ang II and 1-adrenoceptors have been
reported to be involved in at least the first and the third waves of
the response.37 38 69 70 106 Bradykinin possibly
participates as well.109 110 The different control
mechanisms, along with marked neointima proliferation in
the absence of significant changes of media structure, are clear
examples of what above has been referred to as intravascular
heterogeneity.
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Hypertension
Although arterial structural changes may be causally related to
the pathogenesis of both genetic and secondary hypertension, we are not
aware of attempts to type and characterize possible subpopulations of
SMCs that actually participate in the structural response. Especially
in genetic hypertension, in which structural alterations start during
development, not all SMCs may participate to the same extent. Markers
of the contractile phenotype of SMCs, such as smooth muscle -actin,
desmin, and smooth muscle myosin heavy chains, do not emerge
simultaneously in the aorta of developing rats.114 Thus,
in young rats, at least the aorta is a mosaic of SMCs with different
degrees of differentiation. Since there are indications that the degree
of differentiation affects the susceptibility of SMCs to
mitogens,115 116 it is attractive to hypothesize that a
subset of SMCs may play a key role in arterial structural changes
during the development of genetic hypertension.
Pharmacological Interventions
Most drug intervention studies lack the spatial resolution
required to strengthen the occurrence of intravascular heterogeneity.
In most cases, it is not clear whether the structural alteration
observed during treatment is due to a direct action on the vessel wall
or is a result of altered hemodynamics, nerve activity, or plasma
hormone levels. However, some findings, with respect to the sympathetic
nervous system, suggest intravascular diversity. The
1-adrenoceptor antagonist doxazosin reduces stimulation
of DNA synthesis elicited by Ang II in injured arteries to a larger
extent in the original media than in the developing
neointima.117 On the other hand, effects of
sympathectomy on the size and synthetic activity of SMCs in blood
vessels of adult animals are restricted to the abluminal border of the
media near the adventitia, where the sympathetic nerve endings are
normally located.89 94
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What Causes Heterogeneity? |
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TopAbstractIntroductionVascular Heterogeneity in...Heterogeneity of Vascular Growth...What Causes Heterogeneity?Summary and PerspectiveReferences |
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Although there are many examples of heterogeneity of arterial structural changes, the origin of this diversity largely remains to be established. Below we consider two possibilities.
Multifactorial Control
Whether dealing with media hypertrophy or neointima
formation, it has become increasingly clear that multiple interacting
stimuli are required and that the response is susceptible to autocrine
and paracrine inhibitory influences.5 16 17 20 118
Examples of this are stimulation of the production of PDGF-AA and
transforming growth factor-ß1 upon exposure of cultured SMCs
to Ang II118 119 as well as the interaction between
the renin-angiotensin and sympathetic systems, which we have stressed
above. The multifactorial nature of SMC growth control is not limited
to these specific examples but has also been documented for
PDGF,120 epidermal growth factor,121 122 and
cytokines.123 124 This raises the possibility that
differences in the supply of any of the mediators involved will
influence the ultimate structural outcome (Fig 2) and
may thus participate in the diversity of structural responses. It will
be clear that there is an exponential relationship between the number
of mediators involved in growth control and the ultimate structural
outcome (Fig 2).
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Sources of paracrine modulators of SMC growth control are unevenly distributed throughout the vasculature. In the intact arterial wall, the components of the vascular renin-angiotensin system are unevenly distributed over periarterial adipocytes, SMCs, and endothelial cells.125 After balloon injury, angiotensinogen,126 ACE, and Ang II receptors103 are also expressed in the neointima. Local concentrations of Ang II and growth responses to the peptide thus may vary throughout the vascular wall. The density and distribution of the various types of perivascular nerves vary considerably throughout the vascular tree127 128 (Fig 3). Also, the relative importance of the endothelium-derived mediators may differ as a function of the medial thickness and the presence of vasa vasorum. Endothelium can release a broad variety of growth factors, cytokines, and growth inhibitors129 130 131 and influence the proliferation of SMCs.24 31 32 101 As nerves do, the endothelium may thus influence the mitogenic condition of the local microenvironment surrounding the SMCs.132 This is also the case for the ECM, the composition of which differs along the vascular tree, possibly as a consequence of local conditions of pulse pressure and flow.133 Various ECM components may bind growth factors and influence the phenotype of SMCs, which in turn can affect their susceptibility to mitogenic conditions.16 20 Thus, the diverse contributions of nerves, endothelium, and the ECM to the microenvironment in the arterial media may promote regional diversity of vascular responses. This is not restricted to differences among vessel types but applies to intravascular heterogeneity as well. Although the endothelium is of course primarily situated at the luminal surface of the vessel, nerves are concentrated near the border between adventitia and media. Opposite concentration gradients for endothelium-derived mediators and neurotransmitters thus exist within the vascular wall (Fig 3). This concentration gradient is more pronounced for thick-walled than for thin-walled vessels. The functional antagonism of nervous and endothelial influences has previously been proposed with respect to the control of vascular tone.127 It has been suggested that in this situation electrical conduction between SMCs tends to coordinate the response of the entire media to locally supplied bioactive agents.127 Growth control, on the other hand, has been suggested to primarily depend on enzymatic systems (such as tyrosine kinases and protein kinase C) and may therefore be more susceptible to local environmental influences than vascular contractility.
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, adrenergic
nerve; 
, nonadrenergic nerve) are indicated, along with
heterogeneous distribution of desmin ([dark cell profiles]; this
intermediate filament protein may be a marker of smooth muscle cell
phenotype or subpopulation). Open arrows indicate influence of
endothelium-derived mediation; closed arrows, influence
of neurotransmitters. EEL indicates external elastic lamina. (Inspired
by References 1, 7, 8, 45, 52, 110, and 129 and unpublished
observations.)
Diversity of SMCs
Besides the supply of multiple stimuli and inhibitors, the
responsiveness of the effector cells, the SMCs, may vary locally
because of the lack of appropriate receptors and enzymes. Diversity of
the effector cells increases the likelihood of heterogeneity (Fig 2).
SMC diversity may be a selective adaptation to the long-term presence
of a specific mediator (tolerance), may be part of a more complex
change in phenotype, or may result from stable differences among
different SMC genotypes. Tolerance and receptor downregulation have
been documented for several acutely acting vasoactive
agents.1 However, whether it also applies to
growth-affecting factors remains to be established. On the other hand,
there is no doubt that SMC phenotype can be
modulated,12 23 97 but such modulation is not required
before SMC proliferation.116 The SMC phenotype is
primarily defined by differential expression of contractile and
cytoskeletal proteins and ultrastructurally by differences in the
abundance of microfilaments, rough endoplasmic reticulum, and Golgi
complexes.12 Although many examples of phenotypic
modulation are available in vitro and in vivo (Table 6),
the molecular control remains poorly defined. Cell
density145 and, possibly related to this, ECM
components146 147 seem to be involved. Phenotypic
modulation may thus represent a long-term variation of the
dynamic interaction of SMCs with their environment. It will be
interesting to devote future research not only to the factors that
influence SMC phenotype but also to the more functional aspects of this
type of SMC diversity.
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Irreversible differences between SMC genotypes can be another explanation for the SMC diversity (Table 6). The monoclonal origin of human atherosclerotic lesions was the first suggestive evidence for the existence of such SMC subpopulations.134 One of the contributing factors may be their embryological origin. The large arteries in the head and neck are invested with SMCs derived from the neural crest, whereas the more distal vessels are invested with SMCs of mesodermal origin.148 149 Thus, at least at the interface, one can find a heterogeneous population of neural crest– and mesoderm-derived SMCs with different properties. Recently, subpopulations of SMCs have been isolated from the uninjured rat thoracic aorta and the neointima formed after injury. The latter show stable changes in culture and express fetal genes, suggesting that they represent unique genotypes.140 141 In several instances, however, it is not clear whether the observed differences are due to changes in phenotype or to different genotypes (see Table 6).
It will be interesting to devote future research not only to the factors that influence SMC phenotype but also to the characterization of the SMC genotypes and their origin as well as the functional consequences of SMC diversity. Are there really discrete SMC subtypes, or are these the extremes of a spectrum? Are SMC subtypes solely characterized by differential expression of contractile and cytoskeletal proteins, or do they also differ with respect to production and vasoactive agents and with respect to the presence of receptors for these mediators? Are these characteristics interrelated, and if so, are they under the control of specific genes?
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Summary and Perspective |
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TopAbstractIntroductionVascular Heterogeneity in...Heterogeneity of Vascular Growth...What Causes Heterogeneity?Summary and PerspectiveReferences |
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Arterial structural changes in experimental hypertension and injury are heterogeneous. As for vascular functional responses, various types and levels of heterogeneity can be discerned. The origin of the differences in structural changes is largely unclear. Two hypotheses were elaborated: (1) regional and temporal variations in the concentration of multiple growth promoters and inhibitors and (2) differences between SMC subtypes in the susceptibility to mediators. These possibilities are not mutually exclusive but may interdigitate to cause heterogeneity of SMC responses at the intervascular and intravascular levels. Future comparative studies using vessels of different vascular beds and branching order and using experimental approaches with a spatial resolution sufficient to discriminate between changes in individual cells may strengthen these hypotheses. When added to the existing information derived from culture and injury models, these hypotheses may help to better define cellular and molecular targets for the prevention and reduction of specific arterial structural changes in diseases.
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Acknowledgments |
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This work was supported by grants from the Royal Dutch Academy of Sciences (KNAW) and the Netherlands Scientific Research Organisation (NWO).
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References |
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TopAbstractIntroductionVascular Heterogeneity in...Heterogeneity of Vascular Growth...What Causes Heterogeneity?Summary and PerspectiveReferences |
|---|
1. Mulvany MJ, Aalkjaer C. Structure and function of small arteries. Physiol Rev. 1990;70:921-961.
2. Vanhoutte PM. Heterogeneity in vascular smooth muscle. In: Kaley G, Altura BM, eds. Microcirculation. Baltimore, Md: University Park Press; 1978;2:181-309.
3.
Shin WS, Toyo-oka T, Masuo M, Okai Y, Fujita H, Sugimoto T.
Subpopulations of rat vascular smooth muscle cells as discriminated by
calcium release mechanisms from internal stores. Circ
Res. 1991;69:551-556.
4. Bendhack LM, Sharma RV, Bhalla RC. Altered signal transduction in vascular smooth muscle cells of spontaneously hypertensive rats. Hypertension. 1992;19(suppl II):II-142-II-148.
5.
Schwartz SM, Campbell GR, Campbell JH. Replication of
smooth muscle cells in vascular disease. Circ Res. 1986;58:427-444.
6. Schwartz SM, Reidy MA. Common mechanisms of proliferation of smooth muscle in atherosclerosis and hypertension. Hum Pathol. 1987;18:240-247. [Medline] [Order article via Infotrieve]
7. Lee RMKW, Forrest JB, Garfield RE, Daniel EE. Comparison of blood vessel wall dimensions in normotensive and hypertensive rats by histometric and morphometric methods. Blood Vessels. 1983;20:245-254. [Medline] [Order article via Infotrieve]
8.
Owens GK, Schwartz SM, McCanna M. Evaluation of medial
hypertrophy in resistance vessels of spontaneously hypertensive rats.
Hypertension. 1988;11:198-207.
9. Glagov S, Rowley DA, Kohut R. Atherosclerosis of human aorta and its coronary and renal arteries. Arch Pharmacol. 1961;72:82-95.
10.
Gordon D, Reidy MA, Benditt EP, Schwartz SM. Cell
proliferation in human coronary arteries. Proc Natl Acad Sci
U S A. 1990;87:4600-4604.
11. Nobuyoshi M, Kimura T, Ohishi H, Horuchi H, Nosaka H, Hamasaki N, Yokoi H, Koutoka K. Restenosis after percutaneous transluminal coronary angioplasty: pathologic observations in 20 patients. J Am Coll Cardiol. 1991;17:433-439. [Abstract]
12. Chamley-Campbell J, Campbell GR, Ross R. The smooth muscle cell in culture. Physiol Rev. 1979;59:2-51.
13.
Owens GK, Schwartz SM. Alternations in vascular smooth
muscle cell mass in the spontaneously hypertensive rat.
Circ Res. 1982;51:280-289.
14. Clowes AW, Reidy MA, Clowes MM. Mechanisms of stenosis after arterial injury. Lab Invest. 1983;49:208-215. [Medline] [Order article via Infotrieve]
15.
Bevan JA, Joyce EH. Flow-induced resistance artery tone:
balance between constrictor and dilator mechanisms. Am J
Physiol. 1990;258:H663-H668.
16. Scott-Burden T, Resink TJ, Hahn AWA, Bühler FR. Vasoactive peptides and growth factors in the pathophysiology of hypertension. J Cardiovasc Pharmacol. 1992;20(suppl 1):S55-S64.
17. Bondjers G, Glukhova M, Hansson GK, Postnov YV, Reidy MA, Schwartz SM. Hypertension and atherosclerosis: cause and effect, or two effects with one unknown cause? Circulation. 1991;84(suppl VI):VI-12-VI-16.
18.
Owens GK. Control of hypertrophic versus hyperplastic
growth of vascular smooth muscle cells. Am J Physiol. 1989;257:H1755-H1765.
19. Nilsson J. Growth factors and the pathogenesis of atherosclerosis. Atherosclerosis. 1986;62:185-199. [Medline] [Order article via Infotrieve]
20.
Thyberg J, Hedin U, Sjolund M, Palmberg L, Bottger BA.
Regulation of differentiated properties and proliferation of arterial
smooth muscle cells. Arteriosclerosis. 1990;10:966-990.
21. Furchgott RF, Vanhoutte PM. Endothelium-derived relaxing and contracting factors. FASEB J. 1989;3:2007-2018. [Abstract]
22.
Gryglewsky RJ, Bunting RM, Vane JR. Mediators produced by
the endothelial cell. Hypertension. 1988;12:530-548.
23.
Folkow B. Physiological aspects of primary hypertension.
Physiol Rev. 1982;62:347-504.
24. De Mey JGR, Uitendaal MP, Boonen HCM, Schiffers PMH, Fazzi GE. Growth responses in isolated elastic, muscular and resistance-sized arterial segments of the rat. Blood Vessels. 1991; 28:372-385.
25.
Majesky M, Benditt EM, Schwartz SM. Expression and
developmental control of PDGF chain and ß-chain gene in aortic smooth
muscle cells. Proc Natl Acad Sci U S A. 1988;85:1524-1528.
26.
Gordon D, Mohai L, Schwartz S. Induction of polyploidy in
cultures of neonatal rat aortic smooth muscle cells.
Circ Res. 1986;59:633-644.
27.
Hadrava V, Tremblay J, Hamet P. Abnormalities in growth
characteristics of aortic smooth muscle cells in spontaneously
hypertensive rats. Hypertension. 1989;13:589-597.
28.
Hamet P, Hadrava V, Kruppa U, Tremblay J. Transforming
growth factor ß1 expression and effect in aortic smooth muscle cells
from spontaneously hypertensive rats.
Hypertension. 1991;17:896-901.
29. Resink TJ, Scott-Burden T, Baur U, Bühler FR. Increased proliferation rate and phosphoinositide turnover in cultured smooth muscle cells from SHR. J Hypertens. 1987;5:S145-S148.
30. Scott-Burden T, Resink TJ, Bühler FR. Enhanced growth and growth responsiveness of vascular smooth muscle cells from hypertensive rats. J Cardiovasc Pharmacol. 1989;14(suppl):16-21.
31. Angelini GD, Soyombo AA, Newby AC. Smooth muscle cell proliferation in response to injury in an organ culture of human saphenous vein. Eur J Vasc Surg. 1991;5:5-12. [Medline] [Order article via Infotrieve]
32. Koo EWY, Gotlieb AI. Endothelial stimulation of intimal cell proliferation in a porcine aortic organ culture. Am J Pathol. 1989;134:497-503. [Abstract]
33. Fingerle J, Kraft T. The induction of smooth muscle cell proliferation in vitro using an organ culture system. Int Angiol. 1987;6:65-72. [Medline] [Order article via Infotrieve]
34. Southgate K, Newby AC. Serum-induced proliferation of rabbit aortic smooth muscle cells from the contractile state is inhibited by 8-Br-cAMP but not 8-Br-cGMP. Atherosclerosis. 1990;82:113-123. [Medline] [Order article via Infotrieve]
35.
Boonen HCM, Schiffers PMH, Fazzi GE, Janssen GMJ, Daemen
MJAP, De Mey JGR. DNA synthesis in isolated arteries: kinetics and
structural consequences. Am J Physiol. 1991;260:H210-H217.
36. Baumgartner H. Eine neue Methode zur Erzeugung von Thromben durch geziehlte Überdehnung des Gefasswand. Z Ges Exp Med. 1963;137:227-231.
37. Osterrieder W, Muller RK, Powell JS, Clozel JP, Hefti F, Baumgartner HR. Role of angiotensin II in injury-induced neointima formation in rats. Hypertension. 1991;18(suppl II):II-60-II-64.
38.
Daemen MJAP, Lombardi DM, Bosman FT, Schwartz SM.
Angiotensin II induces smooth muscle cell proliferation in the normal
and injured rat arterial wall. Circ Res. 1991;68:450-456.
39. Clozel JP, Hess P, Michael C, Schietinger K, Baumgartner HR. Inhibition of converting enzyme and neointima formation after vascular injury in rabbits and guinea pigs. Hypertension. 1991;18(suppl II):II-55-II-59.
40. Azuma H, Niimi Y, Hamasaki H. Prevention of intimal thickening after endothelial removal by a nonpeptide angiotensin II receptor antagonist, losartan. Br J Pharmacol. 1992;106:665-671. [Medline] [Order article via Infotrieve]
41. Clowes AW, Reidy MA, Clowes MM. Kinetics of cellular proliferation after arterial injury, I: smooth muscle growth in the absence of endothelium. Lab Invest. 1983;49:327-333. [Medline] [Order article via Infotrieve]
42. Black MJ, Campbell JH, Campbell GR. Does smooth muscle cell polyploidy occur in resistance vessels of spontaneously hypertensive rats? Blood Vessels. 1988;25:89-100. [Medline] [Order article via Infotrieve]
43. Mangiarua EI, Lee RMKW. Morphometric study of cerebral arteries from spontaneously hypertensive stroke-prone hypertensive rats. J Hypertens. 1992;10:1183-1190. [Medline] [Order article via Infotrieve]
44.
Baumbach GL, Heistad DD. Remodeling of cerebral arterioles
in chronic hypertension. Hypertension. 1989;13:968-972.
45.
Lee RMKW, Triggle CR, Cheung DWT, Coughlin MD. Structural
and functional consequences of neonatal sympathectomy on the blood
vessels of spontaneously hypertensive rats.
Hypertension. 1987;10:328-338.
46. Mulvany MJ, Baandrup U, Gundersen HJG. Evidence for hyperplasia in mesenteric resistance vessels of spontaneously hypertensive rats using a three-dimensional dissector. Circ Res. 1985; 57:794-800.
47.
Miller MJ, Connors BA, Bohlen HG, Evan AP. Cell and wall
morphology of intestinal arterioles from 4- to 6- and 17- to
19-week-old WKY and SHR. Hypertension. 1987;9:59-69.
48. Bohlen HG. The microcirculation in hypertension. J Hypertens. 1989;7:S117-S124.
49. Smeda JS, Lee RMKW, Forrest JB. Structural and reactivity alterations of the renal vasculature of spontaneously hypertensive rats prior to and during established hypertension. Circ Res. 1988; 63:518-533.
50.
Skov K, Mulvany MJ, Korsgaard N. Morphology of renal
afferent arterioles in spontaneously hypertensive rats.
Hypertension. 1992;20:821-827.
51. Lee RMKW. Structural alterations of blood vessels in hypertensive rats. Can J Pharmacol. 1987;65:1528-1535.
52. Lee RMKW, Garfield RE, Forrest JB, Daniel EE. Morphometric study of structural changes in the mesenteric blood vessels of spontaneously hypertensive rats. Blood Vessels. 1983;20:57-71. [Medline] [Order article via Infotrieve]
53.
Mulvany MJ, Hansen PK, Aalkjaer C. Direct evidence that the
greater contractility of resistance vessels in spontaneously
hypertensive rats is associated with a narrowed lumen, a thickened
media, and an increased number of smooth muscle cell layers.
Circ Res. 1978;43:854-864.
54.
Lombardi D, Owens G, Schwartz SM. Ploidy in mesenteric
vessels of SHR and WKY. Hypertension. 1989;13:475-479.
55.
Bohlen HG. Localization of vascular resistance changes
during hypertension. Hypertension. 1986;8:181-183.
56.
Le Noble JLML, Smith TL, Hutchins PM, Struyker-Boudier HAJ.
Microvascular alterations in adult conscious spontaneously hypertensive
rats. Hypertension. 1990;15:415-419.
57. Le Noble JLML, Tangelder GJ, Slaaf DW, van Essen H, Reneman RS, Struyker-Boudier HAJ. A functional morphometric study of the cremaster muscle microcirculation in young spontaneously hypertensive rats. J Hypertens. 1990;8:741-749. [Medline] [Order article via Infotrieve]
58. Prewitt RL, Chen IIH, Dowell R. Development of microvascular rarefaction in the spontaneously hypertensive rat. Am J Physiol. 1982;243:H243-H251.
59.
Wang DH, Prewitt RL. Microvascular development during normal
growth and reduced blood flow: introduction of a new model. Am J
Physiol. 1991;260:H1966-H1972.
60. Korner PI, Angus JA. Structural determinants of vascular resistance properties in hypertension. J Vasc Res. 1992;29:293-312. [Medline] [Order article via Infotrieve]
61.
Korsgaard N, Mulvany MJ. Cellular hypertrophy in mesenteric
resistance vessels from renal hypertensive rats.
Hypertension. 1988;12:162-167.
62. Thybo NK, Korsgaard N, Mulvany MJ. Morphology and function of mesenteric resistance arteries in transgenic rats with low-renin hypertension. J Hypertens. 1992;10:1191-1196. [Medline] [Order article via Infotrieve]
63.
Korsgaard N, Aalkjaer C, Heagerty AM, Izzard AS, Mulvany MJ.
Histology of subcutaneous small arteries from patients with essential
hypertension. Hypertension. 1993;22:523-526.
64. Yang H, Morto W, Lee RMKW, Kajetanowicz A, Forrest JB. Autoradiographic study of smooth muscle cell proliferation in spontaneously hypertensive rats. Clin Sci. 1989;76:475-478. [Medline] [Order article via Infotrieve]
65. De Mey JGR, Daemen MJAP, Boonen HCM, Bosman FT, Dijkstra EH, Fazzi GE, Janssen GMJ, Schiffers PMH, Struyker-Boudier HAJ, Vrijdag MJJF. In vivo DNA synthesis is not uniformly increased in arterial smooth muscle of young spontaneously hypertensive rats. J Hypertens. 1991;9:695-701. [Medline] [Order article via Infotrieve]
66. Loeb AL, Bean BL. Antihypertensive drugs inhibit hypertension-associated aortic DNA synthesis in the rat. Hypertension. 1986; 8:1135-1142.
67. Lee RMKW. Structural and functional consequences of antihypertensive treatments on blood vessels. In: Lee RMKW, ed. Blood Vessel Changes in Hypertension: Structure and Function. Boca Raton, Fla: CRC Press Inc; 1989; 1:163-190.
68.
Jackson CL, Schwartz SM. Pharmacology of smooth muscle
replication. Hypertension. 1986;20:713-736.
69.
Powell JS, Clozel JP, Muller R, Kuhn H, Hefti F, Hosang M,
Baumgartner H. Inhibitors of angiotensin-converting enzyme prevent
myointimal proliferation after vascular injury. Science. 1989;245:186-188.
70. O'Malley MK, McDermott E, Mehigan D, Higgins N. Role for prazosin in reducing the development of rabbit intimal hyperplasia after endothelial denudation. Br J Surg. 1989;76:936-938. [Medline] [Order article via Infotrieve]
71. Fingerle J, Sanders KH, Fotev Z. Alpha-1-receptor antagonists urapadil and prazosin inhibit neointima formation in rat carotid artery induced by balloon catheter injury. Basic Res Cardiol. 1991;86(suppl 1):75-82.
72.
Van Kleef EM, Smits JFM, De Mey JGR, Cleutjens JPM, Lombardi
DM, Schwartz SM, Daemen MJAP. Alpha-1 adrenoceptor blockade reduces the
angiotensin II induced vascular smooth muscle cell DNA synthesis in the
rat thoracic aorta and carotid artery. Circ Res. 1992;70:1122-1127.
73. Prescott MF, Webb RL, Reidy MA. Angiotensin-converting enzyme inhibitor versus angiotensin II, AT1 receptor antagonist: effects on smooth muscle cell migration and proliferation after balloon catheter injury. Am J Pathol. 1991;139:1291-1296. [Abstract]
74. Capron L, Heudes D, Chajara A, Bruneval P. Effect of ramipril, an inhibitor of angiotensin converting enzyme, on the response of rat thoracic aorta to injury with a balloon catheter. J Cardiovasc Pharmacol. 1991;18:207-218. [Medline] [Order article via Infotrieve]
75. Hanson SR, Powell JS, Dodoson T, Lumsden A, Kelly AB, Anderson JS, Clowes AW, Harker LA. Effects of angiotensin converting enzyme inhibition with cilazapril on intimal hyperplasia in injured arteries and vascular grafts in the baboon. Hypertension. 1991;18(suppl II):II-70-II-76.
76.
Lam JY, Lacoste L, Bourassa MG. Cilazapril and early
atherosclerotic changes after balloon injury of porcine carotid
arteries. Circulation. 1992;85:1542-1547.
77.
Mercator study. Does the new angiotensin converting enzyme
inhibitor cilazapril prevent restenosis after percutaneous transluminal
coronary angioplasty? Circulation. 1992;86:100-110.
78. Viswanathan M, Stromberg C, Seitzer A, Saavedra S. Balloon angioplasty enhances the expression of angiotensin II AT1 receptors in neointima of rat aorta. J Clin Invest. 1992;90:1707-1712.
79.
Janiak P, Pillon A, Prost JF, Vilaine JP. Role of
angiotensin subtype 2 receptor in neointima formation after
vascular injury. Hypertension. 1992;20:737-745.
80. Laporte S, Escher E. Neointima formation after vascular injury is angiotensin II dependent. Biochem Biophys Res Commun. 1992;187:1510-1516. [Medline] [Order article via Infotrieve]
81. Mulvany MJ. Structure and function of small arteries in hypertension. J Hypertens. 1990;8:S225-S232.
82. King RA, Smith RM, Krishman R, Cleary EG. Effects of enalapril and hydralazine treatment and withdrawal upon cardiovascular hypertrophy in stroke-prone spontaneously hypertensive rats. J Hypertens. 1992;10:919-928. [Medline] [Order article via Infotrieve]
83. Black MJ, Adams MA, Bobik A, Campbell JH, Campbell GR. Effect of enalapril on aortic smooth muscle cell polyploidy in the spontaneously hypertensive rat. J Hypertens. 1989;7:997-1003. [Medline] [Order article via Infotrieve]
84. Boonen HCM, Daemen MJAP, Eerdmans PE, Fazzi GE, van Kleef E, Schiffers PMH, De Mey JGR. Mesenteric small artery changes following vasoconstrictor infusion in young rats. J Cardiovasc Pharmacol. 1993;22:388-395. [Medline] [Order article via Infotrieve]
85.
Majesky M, Daemen M, Schwartz S. Alpha-adrenergic
stimulation of platelet-derived growth factor A chain gene expression
in rat aorta. J Biol Chem. 1990;265:1082-1088.
86.
Bevan RD. Effect of sympathetic denervation on smooth muscle
cell proliferation in the growing rabbit ear artery.
Circ Res. 1975;37:14-19.
87.
Bevan RD, Tsuru H. Functional and structural changes in the
rabbit ear artery after sympathetic denervation. Circ
Res. 1981;49:478-485.
88. Bevan RD, Tsuru H, Bevan JA. Cerebral artery mass in the rabbit is reduced by chronic sympathetic denervation. Stroke. 1983; 14:393-396.
89. Branco D, Albino-Teixeria A, Azevedo I, Osswald W. Structural and functional alterations caused at the extraneuronal level by sympathetic denervation of blood vessels. Naunyn Schmiedebergs Arch Pharmacol. 1984;326:302-312. [Medline] [Order article via Infotrieve]
90. Dimitriadou V, Aubineau P, Taxi J, Seylaz J. Ultrastructural changes in the cerebral artery wall induced by long-term sympathetic denervation. Blood Vessels. 1988;25:122-143. [Medline] [Order article via Infotrieve]
91. Froneck K, Bloor CM, Amiel D, Chvapil M. Effect of long term sympathectomy on the arterial wall in rabbits and rats. Exp Mol Pathol. 1978;28:279-289. [Medline] [Order article via Infotrieve]
92. Froneck K. Trophic effects of the sympathetic nervous system on vascular smooth muscle. Ann Biomed Eng. 1983;11:607-615. [Medline] [Order article via Infotrieve]
93. Azevedo I, Osswald W. Trophic role of the sympathetic innervation. Journal de Pharmacologie. 1986;17(suppl II):30-35.
94. Albino-Teixeria A, Azevedo I, Branco D, Osswald W. Purine agonists prevent trophic changes caused by sympathetic denervation. Eur J Pharmacol. 1990;179:141-149. [Medline] [Order article via Infotrieve]
95. Sachinidis A, Ko Y, Nettekoven W, Wieczorek AJ, Dusing R, Vetter H. The effect of angiotensin II on DNA synthesis varies considerably in vascular smooth muscle cells of different Wistar-Kyoto rats. J Hypertens. 1992;10:1159-1164. [Medline] [Order article via Infotrieve]
96. Chamley-Campbell JH, Campbell GR. What controls smooth muscle phenotype? Atherosclerosis. 1981;40:347-357. [Medline] [Order article via Infotrieve]
97. Gabbiani G, Kocher O, Bloom W, Vandekerckhove J, Weber K. Actin expression in smooth muscle cells of rat aortic intimal thickening, human atherosclerotic plaque and cultured rat aortic media. J Clin Invest. 1984;73:148-152.
98. Kocher O, Gabbiani F, Gabbiani G, Reidy MA, Cokay MS, Peters H, Huttner I. Phenotypic features of smooth muscle cells during the evolution of experimental carotid artery intimal thickening: biochemical and morphological studies. Lab Invest. 1991;65:459-470. [Medline] [Order article via Infotrieve]
99. Kocher O, Skalli O, Bloom W, Gabbiani G. Cytoskeleton of rat aortic smooth muscle cells. Lab Invest. 1980;50:645-652.[Medline] [Order article via Infotrieve]
100.
Rothman A, Kulik TJ, Taubman MB, Berk BC, Smith CWJ,
Nadal-Ginard B. Development and characterization of a cloned rat
pulmonary arterial smooth muscle cell line that maintains
differentiated properties through multiple subcultures.
Circulation. 1992;86:1977-1986.
101.
De Mey JGR, Dijkstra EH, Vrijdag MJJF. Endothelium reduces
DNA synthesis in isolated arteries. Am J Physiol. 1991;260:H1128-H1134.
102.
Lindner V, Lappi D, Baird A, Majack R, Reidy M. Role of
fibroblast growth factor in vascular lesion formation.
Circ Res. 1991;68:106-114.
103. Lindner V, Majack RA, Reidy MA. Basic fibroblast growth factor stimulates endothelial regrowth and proliferation in denuded arteries. J Clin Invest. 1990;85:2004-2008.
104.
Majesky M, Schwartz S, Clowes M, Clowes A. Heparin regulates
smooth muscle S phase entry in the injured rat carotid artery.
Circ Res. 1987;61:296-300.
105.
Clowes AW, Clowes MM, Au YPT, Reidy MA, Belin D. Smooth
muscle cells express urokinase during mitogenesis and tissue-type
plasminogen activator during migration in injured rat carotid artery.
Circ Res. 1990;67:61-67.
106. Jackson C, Bush R, Bowyer D. Inhibitory effect of calcium antagonists on balloon catheter-induced arterial smooth muscle cell proliferation and lesion size. Atherosclerosis. 1988;69:115-122. [Medline] [Order article via Infotrieve]
107. Jawien A, Bowen-Pope DF, Lindner V, Schwartz SM, Clowes AW. Platelet-derived growth factor promotes smooth muscle migration and intimal thickening in a rat model of balloon angioplasty. J Clin Invest. 1992;89:507-511.
108. Majesky MW, Lindner V, Twardzik DR, Schwartz SM, Reidy MA. Production of transforming growth factor ß1 during repair of arterial injury. J Clin Invest. 1991;88:904-910.
109. Farhy RD, Ho K-L, Carretero OA, Scicli AG. Kinins mediate the antiproliferative effect of ramipril in rat carotid artery. Biochem Biophys Res Commun. 1992;182:283-288. [Medline] [Order article via Infotrieve]
110.
Farhy RD, Carretero OA, Ho K-L, Scicli AG. Role of kinins and
nitric oxide in the effects of angiotensin converting enzyme inhibitors
on neointima formation. Circ Res. 1993;72:1202-1210.
111.
Fingerle J, Au T, Clowes A, Reidy M. Intimal lesion formation
in rat carotid arteries after endothelial denudation in absence of
medial injury. Arterioscler Thromb. 1990;10:1082-1087.
112.
Clowes A, Schwartz S. Significance of quiescent smooth muscle
migration in the injured rat carotid artery. Circ
Res. 1985;56:139-145.
113. Olson NE, Chao S, Lindner V, Reidy MA. Intimal smooth muscle cell proliferation after balloon catheter injury: the role of basic fibroblast growth factor. Am J Pathol. 1992;140:1017-1023. [Abstract]
114.
Kocher O, Skalli O, Cerutti D, Gabbiani F, Gabbiani G.
Cytoskeletal features of rat aortic cells during development.
Circ Res. 1985;56:829-838.
115.
Blank R, Thompson M, Owens GK. Cell cycle versus density
dependency of smooth muscle alpha actin expression in cultured rat
aortic SMC. J Cell Biol. 1988;107:299-306.
116.
Owens G. Differential effects of antihypertensive drug
therapy on vascular smooth muscle cell hypertrophy, hyperploidy, and
hyperplasia in the SHR. Circ Res. 1985;56:525-536.
117.
Van Kleef E. Angiotensin II Induced DNA Growth Effects
in the Vessel Wall: Role of 1-Adrenoreceptors.
Maastricht, Netherlands: University of Limburg. PhD thesis.
118. Gibbons GH, Pratt RE, Dzau VJ. Vascular smooth muscle cell hypertrophy vs. hyperplasia. J Clin Invest. 1992;90:451-461.
119. Naftilan A, Pratt E, Dzau V. Induction of PDGF-A chain and c-myc gene expressions by angiotensin II in cultured rat vascular smooth muscle cells. J Clin Invest. 1989;83:1419-1424.
120.
Raines E, Dower S, Ross R. Interleukin 1 mitogenic activity
for fibroblasts and smooth muscle cells is due to PDGF-AA.
Science. 1989;243:393-396.
121. Muramatsu I. Vascular actions of epidermal-growth-factor urogastrone: possible relationship to prostaglandin production. Can J Physiol Pharmacol. 1985;63:994-999. [Medline] [Order article via Infotrieve]
122. Reilly CF, Fritze LMS, Rosenberg RD. Heparine-like molecules regulate the number of epidermal growth factor receptors on vascular smooth muscle cells. J Cell Physiol. 1988;136:23-32. [Medline] [Order article via Infotrieve]
123.
Warner BJ, 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.
124. Libby P, Warner SJ, 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.
125.
Campbell D, Habener J. Cellular localization of
angiotensinogen gene expression in brown adipose tissue and mesentery.
Endocrinology. 1987;121:1616-1626.
126.
Rakugi H, Jacob HJ, Hrieger JE, Ingelfinger JR, Pratt RE.
Vascular injury induces angiotensinogen expression in the media and
neointima. Circulation. 1993;87:283-290.
127. Burnstock G. Local mechanisms of blood flow control by perivascular nerves and endothelium. J Hypertens. 1990;8(suppl):95-106.
128. Cowen T, Burnstock G. Quantitative analysis of the density and pattern of adrenergic innervation of blood vessels. Histochemistry. 1980;66:19-34. [Medline] [Order article via Infotrieve]
129. Davies PF. Vascular cell interactions with special reference to the pathogenesis of atherosclerosis. Lab Invest. 1986;55:5-24. [Medline] [Order article via Infotrieve]
130. Moncada S, Palmer RMJ, Higgs EA. Biosynthesis of nitric oxide from L-arginine: a pathway for the regulation of cell function and communication. Biochem Pharmacol. 1989;38:1709-1715. [Medline] [Order article via Infotrieve]
131. Mantovani A, Dejana E. Cytokines as communication signals between leukocytes and endothelial cells. Immunol Today. 1989;10:370-375. [Medline] [Order article via Infotrieve]
132. De Mey JGR, Schiffers PM. Effect of the endothelium on growth responses in arteries. J Cardiovasc Pharmacol. 1993;21(suppl 1):S22-S25.
133. Cox RH. Mechanical properties of arteries in hypertension. In: Lee RMKW, ed. Blood Vessel Changes in Hypertension: Structure and Function. 1st ed. Boca Raton, Fla: CRC Press; 1989; 1:65-98.
134.
Benditt EP, Benditt JM. Evidence for a monoclonal origin of
human atherosclerotic plaques. Proc Natl Acad Sci U S A. 1973;70:1753-1756.
135. Blaes N, Bourdillon MC, Daniel-LaMazière JM, Michaille JJ, Andujar M, Covacho C. Isolation of two morphologically distinct cell lines from rat arterial smooth muscle expressing high tumorigenic potentials. In Vitro Cell Dev Biol. 1991;27A:725-734.
136.
Topouzis S, Catravas JD, Ryan JW, Rosenquist TH. Influence of
vascular smooth muscle heterogeneity on angiotensin converting enzyme
activity in chicken embryonic aorta and in endothelial cells in
culture. Circ Res. 1992;71:923-931.
137. Hedin U, Holm J, Hansson GK. Induction of tenascin in rat arterial injury: relationship to altered smooth muscle cell pheno- type. Am J Pathol. 1991;139:649-656. [Abstract]
138.
Glukhova MA, Frid MG, Koteliansky V. Developmental changes in
expression of contractile and cytoskeletal proteins in human aortic
smooth muscle.J Biol Chem. 1990;265:13042-13046.
139. Fager G, Hansson G, Gown A, Larson D, Skalli O, Bondjers G. Human arterial SMC in culture: inverse relationship between proliferation and expression of contractile proteins. In Vitro Cell Dev Biol. 1989;25:511-520. [Medline] [Order article via Infotrieve]
140.
Majesky MW, Giachelli CM, Reidy MA, Schwartz SM. Rat carotid
neointimal smooth muscle cells re-express a developmentally
regulated mRNA phenotype during repair of arterial injury.
Circ Res. 1992;71:759-768.
141. Giachelli C, Bae N, Lombardi D, Majesky M, Schwartz S. Molecular cloning and characterization of 2B7, a rat mRNA which distinguishes smooth muscle cell phenotypes in vitro and is identical to osteopontin (secreted phosphoprotein I, 2aR). Biochem Biophys Res Commun. 1991;177:867-872. [Medline] [Order article via Infotrieve]
142.
Han KM, Liau G. Identification and characterization of
developmentally regulated genes in vascular smooth muscle cells.
Circ Res. 1992;71:711-719.
143.
Pauletto P, Scannapieco G, Borrione AC, Zanellato AM, Tonello
M, Giuriato L, Pessina AC, Paul CD, Sartore S. A nifedipine sensitive
smooth muscle cell population is present in the atherosclerotic
rabbit aorta. Arterioscler Thromb. 1991;11:928-939.
144. Dartsch PC, Voisard R, Betz E. In vitro characteristics of human atherosclerotic plaque cells: comparison of cells from primary stenosing and restenosing lesions of peripheral and coronary arteries. Res Exp Med (Berl). 1990;190:77-87. [Medline] [Order article via Infotrieve]
145.
De Mey JGR, Vanhoutte PM. Uneven distribution of
postjunctional 1- and 2- like
adrenoceptors in canine arterial and venous smooth muscle.
Circ Res. 1981;48:875-884.
146.
Liau G, Chan L. Regulation of extracellular matrix RNA levels
in cultured SMC. J Biol Chem. 1989;264:10315-10320.
147. Yamamoto M, Yamamoto K, Noumura T. Type I collagen promotes modulation of cultured rabbit arterial smooth muscle cells from a contractile to a synthetic phenotype. Exp Cell Res. 1993;204:121-129. [Medline] [Order article via Infotrieve]
148. Rosenquist TH, McCoy JR, Waldo KL, Kirby ML. Origin and propagation of elastogenesis in the developing cardiovascular system. Anat Rec. 1988;22:860-871.
149. Rosenquist TH, Beall AC, Modis L, Fishman R. Impaired elastic matrix development in the great arteries after ablation of the cardiac neural crest. Anat Rec. 1990;22:347-359.
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M. Adner, E. Uddman, L. O. Cardell, and L. Edvinsson Regional variation in appearance of vascular contractile endothelin-B receptors following organ culture Cardiovasc Res, January 1, 1998; 37(1): 254 - 262. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Pourageaud and J. G. R. De Mey Structural properties of rat mesenteric small arteries after 4-wk exposure to elevated or reduced blood flow Am J Physiol Heart Circ Physiol, October 1, 1997; 273(4): H1699 - H1706. [Abstract] [Full Text] [PDF]
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D. deBlois, B.-S. Tea, T.-V. Dam, J. Tremblay, and P. Hamet Smooth Muscle Apoptosis During Vascular Regression in Spontaneously Hypertensive Rats Hypertension, January 1, 1997; 29(1): 340 - 344. [Abstract] [Full Text] [PDF]
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E. M. van Kleef, J. Fingerle, and M. J.A.P. Daemen Angiotensin II-Induced Progression of Neointimal Thickening in the Balloon-Injured Rat Carotid Artery Is AT1 Receptor Mediated Arterioscler. Thromb. Vasc. Biol., July 1, 1996; 16(7): 857 - 863. [Abstract] [Full Text]
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S. Heeneman, P. J. A. Leenders, P. J. J. W. Aarts, J. F. M. Smits, J. W. Arends, and M. J. A. P. Daemen Peripheral Vascular Alterations During Experimental Heart Failure in the Rat : Do They Exist? Arterioscler. Thromb. Vasc. Biol., September 1, 1995; 15(9): 1503 - 1511. [Abstract] [Full Text]
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