BACKGROUND: The role of the ubiquitin-proteasome system in the vascular senescence and atherosclerotic progression of elderly patients is unclear. We evaluated ubiquitin-proteasome activity in carotid plaques of asymptomatic elderly and adult patients. METHODS: Plaques were obtained from 28 elderly and 18 adult patients undergoing carotid endarterectomy. Plaques were analyzed for ubiquitin levels, proteasome 20S activity, p16 and p53, nitrotyrosine, matrix metalloproteinase-9 (MMP-9) and collagen content (immunohistochemistry and enzyme-linked immunosorbent assay). Serial sections were incubated with specific antibodies anti-human leukocyte antigen (HLA)-DR, anti CD68 and anti-CD3. RESULTS: Compared to plaques obtained from adult patients, plaques of elderly patients had more ubiquitin levels (257.4 +/- 118.9 ng/mg vs 110 +/- 14.4 ng/mg, p <.001), nitrotyrosine (3.8 +/- 0.55 nmol/pg vs 1.1 +/- 0.19 nmol/pg, p <.001), p53 and p16 staining (p <.01), and MMP-9 levels (14.6 +/- 2.5 microg/mg vs 3.2 +/- 0.1.8 microg/mg, p <.001), along with a lesser collagen content (21.9 +/- 4.8% vs 7.1 +/- 2.8%, p <.05) and less proteasome 20S activity (24.2 +/- 6.9 pmol/mg vs 78.4 +/- 10.3 pmol/mg, p <.001). CONCLUSIONS: Our data suggest that reduction of proteasome activity promotes vascular cell senescence, thereby contributing to the pathogenesis of human atherosclerosis.
BACKGROUND: The role of the ubiquitin-proteasome system in the vascular senescence and atherosclerotic progression of elderly patients is unclear. We evaluated ubiquitin-proteasome activity in carotid plaques of asymptomatic elderly and adult patients. METHODS: Plaques were obtained from 28 elderly and 18 adult patients undergoing carotid endarterectomy. Plaques were analyzed for ubiquitin levels, proteasome 20S activity, p16 and p53, nitrotyrosine, matrix metalloproteinase-9 (MMP-9) and collagen content (immunohistochemistry and enzyme-linked immunosorbent assay). Serial sections were incubated with specific antibodies anti-human leukocyte antigen (HLA)-DR, anti CD68 and anti-CD3. RESULTS: Compared to plaques obtained from adult patients, plaques of elderly patients had more ubiquitin levels (257.4 +/- 118.9 ng/mg vs 110 +/- 14.4 ng/mg, p <.001), nitrotyrosine (3.8 +/- 0.55 nmol/pg vs 1.1 +/- 0.19 nmol/pg, p <.001), p53 and p16 staining (p <.01), and MMP-9 levels (14.6 +/- 2.5 microg/mg vs 3.2 +/- 0.1.8 microg/mg, p <.001), along with a lesser collagen content (21.9 +/- 4.8% vs 7.1 +/- 2.8%, p <.05) and less proteasome 20S activity (24.2 +/- 6.9 pmol/mg vs 78.4 +/- 10.3 pmol/mg, p <.001). CONCLUSIONS: Our data suggest that reduction of proteasome activity promotes vascular cell senescence, thereby contributing to the pathogenesis of humanatherosclerosis.
Authors: Monte S Willis; W H Davin Townley-Tilson; Eunice Y Kang; Jonathon W Homeister; Cam Patterson Journal: Circ Res Date: 2010-02-19 Impact factor: 17.367
Authors: Zoltan Ungvari; Anna Csiszar; Danuta Sosnowska; Eva E Philipp; Courtney M Campbell; Philip R McQuary; Tracy T Chow; Miguel Coelho; Elizabeth S Didier; Sara Gelino; Marissa A Holmbeck; Insil Kim; Erik Levy; William E Sonntag; Paul W Whitby; Steven N Austad; Iain Ridgway Journal: J Gerontol A Biol Sci Med Sci Date: 2012-08-17 Impact factor: 6.053
Authors: Zoltan Ungvari; Iain Ridgway; Eva E R Philipp; Courtney M Campbell; Philip McQuary; Tracy Chow; Miguel Coelho; Elizabeth S Didier; Sara Gelino; Marissa A Holmbeck; Insil Kim; Erik Levy; Danuta Sosnowska; William E Sonntag; Steven N Austad; Anna Csiszar Journal: J Gerontol A Biol Sci Med Sci Date: 2011-04-12 Impact factor: 6.053