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• W2058498186 abstract "BackgroundADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) is a recently identified family of extracellular metalloproteinases that has been shown to participate in tissue destruction. We hypothesized that ADAMTS-1 and ADAMTS-4 expression is increased in aortic tissues from patients with thoracic aortic aneurysms and dissections.MethodsWe examined ADAMTS-1 and ADAMTS-4 expression in human descending thoracic aortic aneurysms (n = 14), chronic descending thoracic aortic dissections (n = 16), and descending thoracic aortas from age-matched control organ donors (n = 12). In these tissues, we also evaluated the degradation of versican, a proteoglycan substrate of ADAMTS-1 and ADAMTS-4. In cultured macrophages, we examined whether ADAMTS-4 functions in macrophage infiltration by using a transwell assay.ResultsADAMTS-1 and ADAMTS-4 protein and mRNA expression was significantly higher in thoracic aortic aneurysm and dissection tissues than in control aortic tissues. Double immunofluorescence staining showed the expression of ADAMTS-1 and ADAMTS-4 in smooth muscle cells and macrophages. Consistent with the upregulation of ADAMTS-1 and ADAMTS-4 in thoracic aortic aneurysm and dissection tissues, versican was degraded significantly more in these tissues than in control aortic tissues. In cultured macrophages, transforming growth factor-β increased ADAMTS-4 protein levels and induced macrophage invasion, and the knockdown of ADAMTS-4 reduced cell invasion.ConclusionsIncreased expression of ADAMTS proteins may promote thoracic aortic aneurysm progression by degrading versican and facilitating macrophage invasion. ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) is a recently identified family of extracellular metalloproteinases that has been shown to participate in tissue destruction. We hypothesized that ADAMTS-1 and ADAMTS-4 expression is increased in aortic tissues from patients with thoracic aortic aneurysms and dissections. We examined ADAMTS-1 and ADAMTS-4 expression in human descending thoracic aortic aneurysms (n = 14), chronic descending thoracic aortic dissections (n = 16), and descending thoracic aortas from age-matched control organ donors (n = 12). In these tissues, we also evaluated the degradation of versican, a proteoglycan substrate of ADAMTS-1 and ADAMTS-4. In cultured macrophages, we examined whether ADAMTS-4 functions in macrophage infiltration by using a transwell assay. ADAMTS-1 and ADAMTS-4 protein and mRNA expression was significantly higher in thoracic aortic aneurysm and dissection tissues than in control aortic tissues. Double immunofluorescence staining showed the expression of ADAMTS-1 and ADAMTS-4 in smooth muscle cells and macrophages. Consistent with the upregulation of ADAMTS-1 and ADAMTS-4 in thoracic aortic aneurysm and dissection tissues, versican was degraded significantly more in these tissues than in control aortic tissues. In cultured macrophages, transforming growth factor-β increased ADAMTS-4 protein levels and induced macrophage invasion, and the knockdown of ADAMTS-4 reduced cell invasion. Increased expression of ADAMTS proteins may promote thoracic aortic aneurysm progression by degrading versican and facilitating macrophage invasion." @default.
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• W2058498186 date "2013-02-01" @default.
• W2058498186 modified "2023-09-28" @default.
• W2058498186 title "ADAMTS-1 and ADAMTS-4 Levels Are Elevated in Thoracic Aortic Aneurysms and Dissections" @default.
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• W2058498186 doi "https://doi.org/10.1016/j.athoracsur.2012.10.084" @default.
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