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Transdifferentiation of smooth muscle cells into chondrocytes in atherosclerotic arteries in situ: implications for diffuse intimal calcification


  • Yuri V Bobryshev

    Corresponding author
    1. Surgical Professorial Unit, St Vincent's Hospital Sydney, University of New South Wales, Darlinghurst, Australia
    • Surgical Professorial Unit, Level 5, DeLacy Building, St Vincent's Hospital, Darlinghurst, NSW 2010, Australia.
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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.