Proliferation versus atrophy — the ambivalent role of smooth muscle cells in human atherosclerosis

Schaefer, Hans E.

doi:10.1007/978-3-642-85660-0_5

Cited by 3 publications

(1 citation statement)

References 28 publications

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“…Cells with a similar stellate shape are occasionally observed in the subendothelium of normal and atherosclerotic intima of human aortas, suggesting that these cells may be a normal, albeit rare, component of the vessel wall. [58][59][60] Although this peculiar stellate cell type was first described in the normal aortic intima as early as in 1866 61 and was found to be increased there in the inflammatory state, 62 the nature of arterial myxomatous tissue is still poorly understood. As a component of intimal hyperplasia, stellate cells could originate from SMCs.…”

Section: Discussionmentioning

confidence: 99%

Studies on the Histogenesis of Myxomatous Tissue of Human Coronary Lesions

Tjurmin

Ananyeva

Smith

et al. 1999

ATVB

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Abstract-Myxomatous tissue is a characteristic component of human coronary artery lesions, found more often in restenotic lesions. It represents a bulky accumulation of stellate-shaped cells of unknown histogenesis that are embedded in a loose stroma. We analyzed 64 atherectomy specimens containing substantial amounts of myxomatous tissue by using immunohistochemistry, in situ hybridization, and electron microscopy techniques. Stellate cells represented a heterogeneous population, sharing features of smooth muscle cells (SMCs), macrophages, as well as antigen-presenting dendritic cells. Like quiescent medial SMCs, the stellate cells in all specimens expressed high levels of SM ␣-actin message and protein and showed heterogeneity with respect to heavy-chain myosin, SM22, desmin, and vimentin. Ultrastructurally, stellate cells resembled SMCs, with some peculiarities that distinguish them from both differentiated and dedifferentiated SMCs. In contrast to quiescent SMCs, the stellate cells expressed high levels of acidic fibroblast growth factor mRNA and protein similar to cells of monocyte/macrophage lineage. However, stellate cells did not express the marker of mature macrophages, HAM56, and were heterogeneous with respect to CD68. Moreover, unlike SMCs, the stellate cells bore some of the major phenotypic markers of dendritic cells: they were S100-positive and showed various reactivity with respect to CD1a and human leukocyte antigen (HLA)-DR. Invasion of myxomatous tissue with CD45RO-positive T lymphocytes was correlated with strong expression of CD1a in these specimens. Stellate cells also expressed a pericyte marker, high-molecular-weight melanoma-associated antigen. We conclude that stellate cells of myxomatous tissue represent a specific phenotype of mesenchymal cells (possibly pericytes), which is activated to express some markers of antigen-presenting cells.

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Section: Discussionmentioning

confidence: 99%

Studies on the Histogenesis of Myxomatous Tissue of Human Coronary Lesions

Tjurmin

Ananyeva

Smith

et al. 1999

ATVB

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Smooth Muscle DNA Replication in Response to Angiotensin II Is Regulated Differently in the Neointima and Media at Different Times After Balloon Injury in the Rat Carotid Artery

deBlois

Viswanathan

et al. 1996

ATVB

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We have reported that angiotensin II (Ang II) infusion to rats during the third and fourth weeks after vascular injury stimulates DNA replication in a larger proportion of smooth muscle cells (SMCs) in the arterial neointima than in the underlying media or the normal arterial media. Whether this increased responsiveness to Ang II is a transient or stable property of neointimal cells after vascular injury remained unclear. The present study examined smooth muscle DNA replication in response to Ang II infusion (250 ng.kg-1.min-1 for 2 weeks) at 3 to 4, 9 to 10, or 27 to 28 weeks after balloon injury to the rat carotid artery. Control rats received Ringer's lactate. BrdU (0.8 mg.kg-1.d-1) was coinfused to label replicating DNA. The increased replicative response to Ang II in the neointima versus the normal arterial media did not persist beyond the period of rapid lesion growth shortly after injury, even in neointimal areas without endothelial regeneration. By 9 to 10 weeks after injury, replication frequencies were comparable in the neointima and the normal arterial wall. In the presence of a regenerated endothelium, neointimal DNA replication was lowered but not abolished. After the early period, however, the most marked difference may be the loss of ability of medial SMCs to respond mitogenically to systemic Ang II. As a consequence, Ang II-induced DNA replication in injured arteries was greater in the neointima than in the underlying media at all times studied after injury. DNA replication levels correlated with AT1 receptor levels in the injured artery neointima but not media, as shown by receptor binding in vascular sections at 3 and 10 weeks after injury. The growth response to systemic Ang II is differentially regulated in adjacent smooth muscle layers in the injured arterial wall in vivo via mechanisms that include, but are not restricted to, the regulation of AT1 receptor expression in SMCs.

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Angiotensin II Induction of Osteopontin Expression and DNA Replication in Rat Arteries

deBlois

Lombardi

et al. 1996

Hypertension

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We recently identified the adhesive protein osteopontin as a novel smooth muscle cell product overexpressed in rat developing neointima and human atheroma. Although osteopontin is a candidate stimulant for intimal lesion progression because of its chemotactic and calcium binding functions, factors controlling osteopontin expression in arteries remain poorly defined. In vitro, smooth muscle cell expression of osteopontin is associated with cell cycle transit or alterations in cell phenotype, and it is increased by angiotensin II (Ang II) stimulation. In the present studies, we investigated both osteopontin expression and DNA replication in the arterial wall in response to chronic Ang II infusion in vivo. Rat carotid arteries with or without intimal thickening (induced by balloon catheterization) were examined. Ang II (250 ng/kg per minute) or vehicle was coinfused with bromodeoxyuridine (to label replicating DNA in vivo) for 2 weeks beginning 4 weeks after injury. With Ang II, smooth muscle cells overexpressed osteopontin as shown by protein immunohistochemistry, in situ hybridization, and Northern blot analyses. Osteopontin mRNA levels were increased markedly (approximately fivefold) in the normal artery media and injured artery neointima, but levels remained low in the injured artery media, in positive correlation (R2 = 0.88, P < .001) with DNA replication in the smooth muscle layers, further suggesting that osteopontin may be a growth-associated, phenotype-dependent gene for smooth muscle cells. However, osteopontin expression in neointima was not restricted to areas showing DNA replication, suggesting a nonobligatory association. Ang II induced severe hypertension. Arterial osteopontin expression was increased also by chronic catecholamine infusion, a model of vascular growth stimulation showing labile pressure elevations. Osteopontin induction in smooth muscle cells may contribute to Ang II-dependent intimal lesion progression and vascular remodeling events associated with renovascular diseases or hyperadrenergic disorders.

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Proliferation versus atrophy — the ambivalent role of smooth muscle cells in human atherosclerosis

Cited by 3 publications

References 28 publications

Studies on the Histogenesis of Myxomatous Tissue of Human Coronary Lesions

Studies on the Histogenesis of Myxomatous Tissue of Human Coronary Lesions

Smooth Muscle DNA Replication in Response to Angiotensin II Is Regulated Differently in the Neointima and Media at Different Times After Balloon Injury in the Rat Carotid Artery

Angiotensin II Induction of Osteopontin Expression and DNA Replication in Rat Arteries

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