Transdifferentiation of smooth muscle cells into chondrocytes in atherosclerotic arteries in situ: implications for diffuse intimal calcification.
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 alpha-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.
Bobryshev
Yuri V
YV
Surgical Professorial Unit, St Vincent's Hospital Sydney, University of New South Wales, Darlinghurst, NSW 2010, Australia. y.bobryshev@unsw.edu.au
D000328:Adult; D000368:Aged; D000818:Animals; D001018:Aortic Diseases / Q000378:metabolism / Q000473:pathology; D001161:Arteriosclerosis / Q000378:metabolism / Q000473:pathology*; D002114:Calcinosis / Q000378:metabolism / Q000473:pathology*; D002340:Carotid Artery Diseases / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D019902:Chondrocytes / Q000648:ultrastructure*; D024043:Collagen Type II / Q000378:metabolism; D005260:Female; D006609:High Mobility Group Proteins / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000648:ultrastructure*; D009336:Necrosis; D055758:SOX9 Transcription Factor; D014157:Transcription Factors / Q000378:metabolism
D024043:Collagen Type II; D006609:High Mobility Group Proteins; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; C527933:Sox9 protein, mouse; D014157:Transcription Factors