The origin and differentiation potential of smooth muscle cells in coronary atherosclerosis.
OBJECTIVE
To determine the phenotypical state of smooth muscle cells during the pathogenesis of an atherosclerotic lesion, and to determine the morphological state of the endothelium and the origin of foam cells.


METHODS
Twenty-one samples of atherosclerotically changed right coronary arteries, which were divided into six subgroups based on the stage of atherosclerosis, were analyzed. The tissues were fixed in formalin and embedded in paraffin. Sections of 5 mum thickness were stained immunocytochemically using a labelled streptavidin-biotin/horse radish peroxidase kit (Dako, Denmark) for the identification of vimentin, alpha-smooth muscle actin, myosin heavy chains, desmin, S-100 protein, CD3, CD31, CD34, CD45, CD68 and proliferating cell nuclear antigen protein.


RESULTS
The present study showed that there is first functional and then morphological damage of the endothelium in the late stages of atherosclerosis. The preatheroma stage revealed the presence of intimal changes of smooth muscle cells, with expression of vimentin and alpha-smooth muscle actin and a lack of expression of desmin, which led to a switch to a synthetic phenotype. The described changes progressed into the later stages of atherosclerosis. Along with these changes, a large number of foam cells of variant origin were observed; some of the foam cells developed from monocyte-macrophage lineage (CD68-immunoreactive) and others originated from smooth muscle cells (vimentin- and S-100-immunoreactive). The late stages of atherosclerosis development, such as the atheroma stage, include intimal changes with the formation of a lipid core (S-100-immunoreactive cells and cell necrosis), while fibrosis in the lipid core and the accumulation of collagen fibres with extreme hypocellularity are characteristics of the fibroatheroma stage.
Vukovic
Irena
I
Institute of Histology and Embryology.
Arsenijevic
Nebojsa
N
Lackovic
Vesna
V
Todorovic
Vera
V