An update on clonality: what smooth muscle cell type makes up the atherosclerotic plaque? [version 1; referees: 2 approved]
Almost 50 years ago, Earl Benditt and his son John described the clonality of the atherosclerotic plaque. This led Benditt to propose that the atherosclerotic lesion was a smooth muscle neoplasm, similar to the leiomyomata seen in the uterus of most women. Although the observation of clonality has b...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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F1000 Research Ltd
2018-12-01
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| Series: | F1000Research |
| Online Access: | https://f1000research.com/articles/7-1969/v1 |
| _version_ | 1818296198410272768 |
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| author | Stephen M. Schwartz Renu Virmani Mark W. Majesky |
| author_facet | Stephen M. Schwartz Renu Virmani Mark W. Majesky |
| author_sort | Stephen M. Schwartz |
| collection | DOAJ |
| description | Almost 50 years ago, Earl Benditt and his son John described the clonality of the atherosclerotic plaque. This led Benditt to propose that the atherosclerotic lesion was a smooth muscle neoplasm, similar to the leiomyomata seen in the uterus of most women. Although the observation of clonality has been confirmed many times, interest in the idea that atherosclerosis might be a form of neoplasia waned because of the clinical success of treatments for hyperlipemia and because animal models have made great progress in understanding how lipid accumulates in the plaque and may lead to plaque rupture. Four advances have made it important to reconsider Benditt’s observations. First, we now know that clonality is a property of normal tissue development. Second, this is even true in the vessel wall, where we now know that formation of clonal patches in that wall is part of the development of smooth muscle cells that make up the tunica media of arteries. Third, we know that the intima, the “soil” for development of the human atherosclerotic lesion, develops before the fatty lesions appear. Fourth, while the cells comprising this intima have been called “smooth muscle cells”, we do not have a clear definition of cell type nor do we know if the initial accumulation is clonal. As a result, Benditt’s hypothesis needs to be revisited in terms of changes in how we define smooth muscle cells and the quite distinct developmental origins of the cells that comprise the muscular coats of all arterial walls. Finally, since clonality of the lesions is real, the obvious questions are do these human tumors precede the development of atherosclerosis, how do the clones develop, what cell type gives rise to the clones, and in what ways do the clones provide the soil for development and natural history of atherosclerosis? |
| first_indexed | 2024-12-13T03:59:44Z |
| format | Article |
| id | doaj.art-3545faff7b6e46afa2d63989ec85e579 |
| institution | Directory Open Access Journal |
| issn | 2046-1402 |
| language | English |
| last_indexed | 2024-12-13T03:59:44Z |
| publishDate | 2018-12-01 |
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| series | F1000Research |
| spelling | doaj.art-3545faff7b6e46afa2d63989ec85e5792022-12-22T00:00:30ZengF1000 Research LtdF1000Research2046-14022018-12-01710.12688/f1000research.15994.117469An update on clonality: what smooth muscle cell type makes up the atherosclerotic plaque? [version 1; referees: 2 approved]Stephen M. Schwartz0Renu Virmani1Mark W. Majesky2Pathology, University of Washington, Seattle, WA, 98112, USACV Path Institute, Gaithersberg, Maryland, 20878, USACenter for Developmental Biology and Regenerative Medicine, Seattle Children's Hospital Research Institute, Seattle, WA, 98112, USAAlmost 50 years ago, Earl Benditt and his son John described the clonality of the atherosclerotic plaque. This led Benditt to propose that the atherosclerotic lesion was a smooth muscle neoplasm, similar to the leiomyomata seen in the uterus of most women. Although the observation of clonality has been confirmed many times, interest in the idea that atherosclerosis might be a form of neoplasia waned because of the clinical success of treatments for hyperlipemia and because animal models have made great progress in understanding how lipid accumulates in the plaque and may lead to plaque rupture. Four advances have made it important to reconsider Benditt’s observations. First, we now know that clonality is a property of normal tissue development. Second, this is even true in the vessel wall, where we now know that formation of clonal patches in that wall is part of the development of smooth muscle cells that make up the tunica media of arteries. Third, we know that the intima, the “soil” for development of the human atherosclerotic lesion, develops before the fatty lesions appear. Fourth, while the cells comprising this intima have been called “smooth muscle cells”, we do not have a clear definition of cell type nor do we know if the initial accumulation is clonal. As a result, Benditt’s hypothesis needs to be revisited in terms of changes in how we define smooth muscle cells and the quite distinct developmental origins of the cells that comprise the muscular coats of all arterial walls. Finally, since clonality of the lesions is real, the obvious questions are do these human tumors precede the development of atherosclerosis, how do the clones develop, what cell type gives rise to the clones, and in what ways do the clones provide the soil for development and natural history of atherosclerosis?https://f1000research.com/articles/7-1969/v1 |
| spellingShingle | Stephen M. Schwartz Renu Virmani Mark W. Majesky An update on clonality: what smooth muscle cell type makes up the atherosclerotic plaque? [version 1; referees: 2 approved] F1000Research |
| title | An update on clonality: what smooth muscle cell type makes up the atherosclerotic plaque? [version 1; referees: 2 approved] |
| title_full | An update on clonality: what smooth muscle cell type makes up the atherosclerotic plaque? [version 1; referees: 2 approved] |
| title_fullStr | An update on clonality: what smooth muscle cell type makes up the atherosclerotic plaque? [version 1; referees: 2 approved] |
| title_full_unstemmed | An update on clonality: what smooth muscle cell type makes up the atherosclerotic plaque? [version 1; referees: 2 approved] |
| title_short | An update on clonality: what smooth muscle cell type makes up the atherosclerotic plaque? [version 1; referees: 2 approved] |
| title_sort | update on clonality what smooth muscle cell type makes up the atherosclerotic plaque version 1 referees 2 approved |
| url | https://f1000research.com/articles/7-1969/v1 |
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