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Transdifferentiation of smooth muscle cells into chondrocytes in atherosclerotic arteries in situ : implications for diffuse intimal calcification
Author(s) -
Bobryshev Yuri V
Publication year - 2005
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1743
Subject(s) - transdifferentiation , calcification , pathology , chondrocyte , chemistry , anatomy , cell type , myocyte , immunohistochemistry , microbiology and biotechnology , cell , biology , medicine , cartilage , biochemistry
Several hypotheses have been offered to explain the occurrence of arteriosclerotic calcification but the mechanisms involved are still not well understood. Using a combination of electron microscopy and immunohistochemistry, atherosclerotic plaques from human arteries as well as atherosclerotic‐like lesions from aortas of apo‐E‐deficient mice were examined to identify cell type(s) associated with calcification. Electron microscopic analysis showed that, in human atherosclerotic plaques, chondrocyte‐like cells were present in areas surrounding the necrotic cores. In these areas, some smooth muscle cells displayed features of their transdifferentiation into chondrocyte‐like cells. Immunohistochemical analysis confirmed that smooth muscle cells with a reduced content of α‐smooth muscle actin expressed Sox‐9. Destruction of chondrocytes resulted in the accumulation of numerous membrane‐bound vesicles in the extracellular space. Membrane‐bound vesicles originating from chondrocytes were found to undergo calcification. Similar processes were found to occur in atherosclerotic‐like lesions in apo‐E‐deficient mice. These observations suggest that transdifferentiation of smooth muscle cells into chondrocytes contributes to atherosclerotic calcification. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.