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• W2016065666 abstract "The molecular mechanisms of the atheroprotective effect evoked by hormone replacement therapy in postmenopausal women is not well known. Recently, we have demonstrated enhanced activity of the ubiquitin-proteasome system in human atherosclerotic plaques and evidenced that it is associated with inflammatory-induced plaque rupture. Therefore, we hypothesized that hormone replacement therapy may exert the cardioprotective effects modulating the ubiquitin-proteasome activity. To investigate this possibility, this study examined the differences in inflammatory infiltration, as well as ubiquitin-proteasome activity, between asymptomatic carotid plaques of postmenopausal women with and without concomitant hormone replacement therapy. Plaques were obtained from 20 postmenopausal women treated with hormone replacement therapy (current users) and 32 nontreated women (never-users) enlisted to undergo carotid endarterectomy for extracranial high-grade (>70%) internal carotid artery stenosis. Plaques were analyzed for macrophages, T lymphocytes, human leukocyte antigen-DR+ cells, ubiquitin-proteasome system, nuclear factor κB, inhibitor of nuclear factor κBβ, tumor necrosis factor-α, nitrotyrosine, matrix metalloproteinase-9, and collagen content (immunohistochemistry and ELISA). Compared with plaques from current users, plaques from never-users had more macrophages, T lymphocytes, and human leukocyte antigen-DR+ cells ( P <0.001); more ubiquitin-proteasome activity, tumor necrosis factor-α, and nuclear factor κB ( P <0.001); and more nitrotyrosine and matrix metalloproteinase-9 ( P <0.001), along with a lesser collagen content and inhibitor of nuclear factor κBβ levels ( P <0.001). This study supports the hypothesis that hormone replacement therapy inhibits plaque ubiquitin-proteasome activity by decreasing oxidative stress generation in postmenopausal women. This effect, in turn, might contribute to plaque stabilization by inhibiting the activation of nuclear factor κB–dependent inflammation, responsible for plaque rupture." @default.
• W2016065666 created "2016-06-24" @default.
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• W2016065666 date "2008-04-01" @default.
• W2016065666 modified "2023-09-23" @default.
• W2016065666 title "Proteasome Activity as a Target of Hormone Replacement Therapy–Dependent Plaque Stabilization in Postmenopausal Women" @default.
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• W2016065666 doi "https://doi.org/10.1161/hypertensionaha.107.105239" @default.
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