Studies on the Histogenesis of Myxomatous Tissue of Human Coronary Lesions

Abstract

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.

Activated Interstitial Myofibroblasts Express Catabolic Enzymes and Mediate Matrix Remodeling in Myxomatous Heart Valves

“…These cells can be a local source of multiple cytokines and catabolic enzymes that affect cell proliferation, activation, and ECM accumulation. They can be found in restenotic lesions after angioplasty or stenting, 19 suggesting similar mechanisms of myofibroblast activation, differentiation, proliferation, and ECM degradation.…”

c-kit-Immunopositive vascular progenitor cells populate human coronary in-stent restenosis but not primary atherosclerotic lesions

“…In the restenosis literature, myxoid tissue with these stellate-shaped cells is commonly believed to be a characteristic finding of RS and ISR lesions and presumed evidence of the proliferative nature of this tissue (19). Moreover, Tjurmin and colleagues (28) demonstrated that stellate cells expressed CD1a and HLA-DR antigens and speculated that these cells may form part of an immune response during vascular lesion formation. Blood-borne inflammatory cells are certainly thought to play a key role in the genesis of ISR, and we recently demonstrated that antagonism of VLA-4 to prevent mononuclear cell attachment and transmigration into the vessel wall at least transiently inhibits stent intimal formation (16).…”

Expression of Secretory Group IIA Phospholipase A 2 in Relation to the Presence of Microbial Agents, Macrophage Infiltrates, and Transcripts of Proinflammatory Cytokines in Human Aortic Tissues

“…Other ␣-actin-and sPLA 2 -IIA-positive cells frequently exhibited a typical stellate-shaped appearance. Recently, Tjurmin et al 53 have shown that stellate cells of myxomatous tissue represent a heterogeneous cell population, sharing features of macrophages, smooth muscle cells, and antigenpresenting dendritic cells. The latter cell type is characterized by immunoreactivity with antibodies recognizing ␣-actin, HLA-DR, and CD1a.…”

“…The latter cell type is characterized by immunoreactivity with antibodies recognizing ␣-actin, HLA-DR, and CD1a. 53 Bobryshev et al 10 have argued that in addition to macrophages, at least in part, vascular dendritic (CD1a-positive) cells may be responsible for the sPLA 2 -IIA expression in atherosclerotic plaques. These data suggest that in addition to CD68-positive macrophages, smooth muscle cells, and adventitial fibroblasts, stellate cells may be responsible for the expression of sPLA 2 -IIA identified in atherosclerotic lesions.…”

“…These data suggest that in addition to CD68-positive macrophages, smooth muscle cells, and adventitial fibroblasts, stellate cells may be responsible for the expression of sPLA 2 -IIA identified in atherosclerotic lesions. Interestingly, Tjurmin et al 53 hypothesized that in atherosclerotic lesions, stellate cells might be involved in local immune responses, in which they act as antigen-presenting cells.…”