The Role of Arterial Smooth Muscle Cells in the Pathogenesis of Atherosclerosis

Desmoulière, Alexis; Gabbiani, Giulio

doi:10.1159/000108992

Cited by 22 publications

(7 citation statements)

References 40 publications

(50 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, our results suggest that the loss of these markers during dedifferentiation is also asynchronous. The reduced proportion of cells stained with mature SMC markers (desmin, h-caldesmon) observed in the thickened intima of the hypercholesterolemic FA, compared to the equivalent BA, indicates that atherogenesis is more advanced in the former, in agreement with previous suggestions that cerebral blood vessels are less susceptible than peripheral arteries to develop such pathology [10, 23]. …”

Section: Discussionsupporting

confidence: 90%

“…The second type is the basilar artery (BA), also supplied with a dense plexus of sympathetic fibers which, however, are poorly efficient in constricting it [22]. Furthermore, it is known that cerebral arteries display relatively slight signs of atherosclerosis in conditions where the FA or the aorta are seriously lesioned [23]. These points suggested to us that the protective influence of the sympathetic innervation in cerebral arteries might be particularly significant.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Sympathectomy Causes Aggravated Lesions and Dedifferentiation in Large Rabbit Atherosclerotic Arteries without Involving Nitric Oxide

Kacem¹,

Sercombe²,

Hammami

et al. 2006

J Vasc Res

View full text Add to dashboard Cite

Previously [Histochem J 1997;29:279–286], we found that sympathectomy induced neointima formation in ear but not cerebral arteries of genetically hyperlipidemic rabbits. To clarify the influence of sympathetic nerves in atherosclerosis, and whether their influence involves vascular NO activity, we studied groups of normocholesterolemic intact (NI) and sympathectomized (NS), and hypercholesterolemic intact (HI) and sympathectomized (HS) rabbits (diet/6-hydroxydopamine for 79 days). Segments of basilar (BA) and femoral (FA) arteries were studied histochemically, to evaluate differentiation (anti-desmin, anti-vimentin, anti-h-caldesmon, and nuclear dye), by confocal microscopy, and by in vitro myography. In BAs, staining of NI and NS groups was similar. In hypercholesterolemic groups, a small neointima developed, more frequently in HS segments where smooth muscle cells (SMCs) positive for all antibodies appeared to be migrating into the neointima. In FAs, SMCs stained for the three antibodies in the NI group, but we observed desmin- and h-caldesmon-negative, vimentin-positive cells in some external medial layers of the NS, HI and HS groups, identical to adventitial fibroblasts. Large neointimas of the HS group contained vimentin-positive and largely desmin- and h-caldesmon-negative cells. Relaxation of BA or FA segments to acetylcholine was not decreased by sympathectomy. Sympathectomy increased the contraction of resting FAs to nitro-L-arginine (p = 0.0379). Thus, sympathectomy aggravates the tendency for FA SMCs to migrate and dedifferentiate, increasing atherosclerotic lesions, without decreasing NO activity, but has only minor effects on BAs.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Sympathectomy Causes Aggravated Lesions and Dedifferentiation in Large Rabbit Atherosclerotic Arteries without Involving Nitric Oxide

Kacem¹,

Sercombe²,

Hammami

et al. 2006

J Vasc Res

View full text Add to dashboard Cite

show abstract

“…Freshly isolated IT-15 cells showed a markedly reduced percentage of a-SM actin-, SM my- osin-, and desmin-positive cells compared with UM, RM, and control SMCs (/><.O1), confirming the biochemical data previously reported. 36 Freshly isolated IT-60 cells presented features similar to those of UM, RM, and control SMCs. Table 2 …”

Section: Cell Proliferationmentioning

confidence: 84%

Rat aortic smooth muscle cells isolated from different layers and at different times after endothelial denudation show distinct biological features in vitro.

Orlandi

Ehrlich

Ropraz

et al. 1994

Arterioscler Thromb

102

105

View full text Add to dashboard Cite

Endothelial denudation by balloon injury of the rat aorta induces the development of a neointima as a consequence of the migration and proliferation of smooth muscle cells (SMCs). Initially, intimal SMCs show a dedifferentiated phenotype, which reverts to a normal differentiated phenotype after endothelial cells have resurfaced the vessel lumen. We investigated in vitro the proliferative and phenotypic features of SMCs from different layers of rat aorta isolated 15 and 60 days after endothelial denudation. Freshly isolated intimal cells 15 days after balloon injury (IT-15) appeared rounded and showed a decreased content of a-smooth muscle actin, smooth muscle myosin, and desmin compared with intimal cells isolated 60 days after balloon injury . No morphological and cytoskeletal differences were observed among freshly isolated IT-60 cells and other medial populations, which included medial SMCs that underlie the intimal thickening. In culture, IT-15 cells showed increased proliferative activity both in monolayers and in free-floating collagen lattices. Decreased expression of a-smooth muscle actin and I ntimal thickening after endothelial denudation has been widely used as a model for the development of the atheromatous plaque and has furnished useful information on smooth muscle cell (SMC) susceptibility to microenvironmental stimuli. 16 Only a small proportion of medial SMCs are activated to migrate and replicate after endothelial denudation 5 ; this may reflect a heterogeneity of SMC phenotypic features that has been described by means of several other criteria. 6 " It has been shown that cultured SMCs from the normal media and from the experimental intimal thickening show different growth patterns. SMCs from the intimal thickening, collected 15 days after endothelial lesion, proliferate more actively than do medial cells in the presence of the same amounts of serum; moreover, contrary to medial cells, SMCs are capable of growing in the absence of serum factors. 48This behavior is also seen in normal medial SMCs Received December 17, 1993; revision accepted February 11, 1994.From the Department of Pathology, University of Geneva, Switzerland (A.O., H.P.E., P.R., G.G.); the Department of Pathology, University "Tor Vergata" of Rome, Italy (A.O., L.G.S.); and the Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston (H.P.E.).Reprint requests to Dr Giulio Gabbiani, Department of Pathology, University of Geneva, CMU-1, rue Michel-Servet, CH-1211 Geneva 4, Switzerland. smooth muscle myosin was documented in IT-15 cells compared with IT-60 cells and other medial SMC populations in monolayer. Moreover, IT-15 cells suspended in collagen lattices were poor at contracting these collagen lattices compared with IT-60 and control SMCs. IT-60 cells were equivalent to control SMCs at lattice contraction except for a temporary delay at day 1. Cells from the media underlying the intimal thickening isolated 15 and 60 days after balloon injury proliferated less, had an increased content...

show abstract

“…These changes can be due to microenvironmental influences (eg, the action and/or the absence of cytokines or extracellular matrix components) and/or to intrinsic properties of SMCs (for review see References 3,26,and 27). This last mechanism presupposes a heterogeneity of SMC phenotype.…”

Section: Discussionmentioning

confidence: 99%

Age influences the replicative activity and the differentiation features of cultured rat aortic smooth muscle cell populations and clones.

Bochaton‐Piallat

Gabbiani

Ropraz

et al. 1993

Arterioscler Thromb

View full text Add to dashboard Cite

The replicative activity and the differentiation features of aortic smooth muscle cells (SMCs) cultured as whole populations or clones from newborn (4-day-old), young adult (6-week-old), and old (18-month-old) rats were studied by means of cell counting, [3 H]thymidine incorporation, and measurement of the expression of cytoskeletal proteins and mRNAs. In whole populations at the fifth passage, replicative activity increased and differentiation features (ie, expression of o-smooth muscle actin, desmin, and smooth muscle myosin heavy chains) decreased with increasing age of the donor animal. SMC clones derived from newborn or young adult rats showed more differentiated cytoskeletal features than their parental populations; however, most SMC clones from old rats showed differentiated features similar to those observed in their parental populations. Our results suggest that (1) SMCs of the rat aortic media behave as a heterogeneous population; (2) cultured whole SMC populations behave differently from clones as far as their replicative activity and differentiation features are concerned; and (3) SMCs derived from old rats, whether grown as whole populations or as clones, dedifferentiate more substantially and replicate more actively than corresponding cultures from newborn or young adult rats when submitted to the same amount of serum growth factors; these differences may play a role in arterial development as well as in the formation and evolution of the atheromatous plaque. O ne of the major features of atheromatous plaque development is the increase of the intimal cell population, which is mainly due to medial smooth muscle cell (SMC) migration and proliferation (for review see References 1 to 3). The early observations of Benditt and Benditt 4 suggest that the initial SMC proliferative event must involve a small proportion of the media population, possibly one cell. This may be due to an exogenous or endogenous stimulus affecting a single (or few) cell(s) but may also depend on the fact that SMCs are heterogeneous in their replicative potentiality. It has also been shown that human and experimental atheromatous SMCs show dedifferentiated features, at least as far as their morphology (for review see Reference 5) and cytoskeletal equipment 6 " 9 are concerned, and the above considerations may apply to the acquisition of such features by SMCs. The possible heterogeneity of SMCs has been little explored until now because of the lack of experimental models. A suitable model could be based on the production of SMC clones. Ideally, these clones should be produced from human SMCs; practically, however, clones derived from SMCs of an experimental animal are relatively easy to obtain and may furnish new, useful information on the general biology of arterial SMCs.Received March 30, 1993; revision accepted June 16, 1993. From the Department of Pathology, University of Geneva, Geneva, Switzerland.Correspondence to G. Gabbiani, Department of Pathology, University of Geneva, CMU, 1 Rue Michel Servet, 1211 Geneva 4, Switzerlan...

show abstract

The Role of Arterial Smooth Muscle Cells in the Pathogenesis of Atherosclerosis

Cited by 22 publications

References 40 publications

Sympathectomy Causes Aggravated Lesions and Dedifferentiation in Large Rabbit Atherosclerotic Arteries without Involving Nitric Oxide

Sympathectomy Causes Aggravated Lesions and Dedifferentiation in Large Rabbit Atherosclerotic Arteries without Involving Nitric Oxide

Rat aortic smooth muscle cells isolated from different layers and at different times after endothelial denudation show distinct biological features in vitro.

Age influences the replicative activity and the differentiation features of cultured rat aortic smooth muscle cell populations and clones.

Contact Info

Product

Resources

About