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From the Department of Molecular Cell Biology and Genetics, Cardiovascular Research Institute Maastricht, University of Limburg, Maastricht, Netherlands (F.T.L. van der L., F.C.S.R., G.J.J.M. van E.); University of Geneva (Switzerland), Department of Pathology (G.G.); and University of Glasgow, Department of Obstetrics and Gynecology, UK (G.K.).
Abstract Smoothelin is a constituent of the cytoskeleton
specific for smooth muscle cells (SMCs) in a broad range of species. It
has been postulated that smoothelin represents a marker of
highly differentiated, contractile SMCs. Here, we present data on
the presence of smoothelin in the human vascular system that support
this hypothesis. For this purpose, smoothelin distribution was studied
(1) during vasculogenesis of the placenta, (2) in normal adult blood
vessels, and (3) in atherosclerotic lesions. Smoothelin was first
observed in placental tissue at approximately week 10 to 11 of
gestation. In full-term placenta, it was found in the SMCs of vessels
in the large stem villi and in the chorionic plate. Furthermore, it was
present in the fetal arteries of smaller stem villi, but it was not
found in the veins. In adult blood vessels, a small population of
aortic (
10%) and large muscular artery (
30% to 50%) SMCs was
positive for smoothelin. In general, smoothelin and desmin were
coexpressed in the same SMCs, but expression of desmin appeared to be
less abundant. However, the majority of SMCs in these blood vessels
were smoothelin- and desmin-negative but expressed vimentin, whereas
-smooth muscle actin (
-SMA) was present in all SMCs. The SMCs
in the media of small muscular arteries were positive for smoothelin
and desmin (>95%), whereas the vimentin-positive SMC type was scarce.
Smoothelin was absent in capillaries, pericytic venules, and small
veins but was occasionally observed in the SMCs of large veins. Thus,
the distribution of smoothelin in the SMCs of the vascular system
appears to be limited to blood vessels that are capable of pulsatile
contraction. In atherosclerotic femoral arteries, smoothelin-positive
cells were detected in the media, the atheromatous
plaque, and the intimal thickening. Smoothelin-positive cells were
present primarily at the luminal portion of advanced lesions. The
presence of a considerable number of such smoothelin-positive cells at
that location may indicate that these plaques are no longer expanding.
Key Words: smoothelin smooth muscle cells human blood vessels atherosclerotic lesions differentiation placenta
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