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首页> 外文期刊>The journals of gerontology.Series A. Biological sciences and medical sciences >Effects of ubiquitin-proteasome system deregulation on the vascular senescence and atherosclerosis process in elderly patients.
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Effects of ubiquitin-proteasome system deregulation on the vascular senescence and atherosclerosis process in elderly patients.

机译:泛素-蛋白酶体系统失调对老年患者血管衰老和动脉粥样硬化过程的影响。

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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.
机译:背景:泛素-蛋白酶体系统在老年患者血管衰老和动脉粥样硬化进展中的作用尚不清楚。我们评估了无症状的老年人和成人患者的颈动脉斑块中的泛素-蛋白酶体活性。方法:从28例老年患者和18例成人患者的颈动脉内膜切除术中获得斑块。分析斑块的遍在蛋白水平,蛋白酶体20S活性,p16和p53,硝基酪氨酸,基质金属蛋白酶9(MMP-9)和胶原蛋白含量(免疫组化和酶联免疫吸附测定)。将连续切片与抗人白细胞抗原(HLA)-DR,抗CD68和抗CD3的特异性抗体一起孵育。结果:与成年斑块相比,老年患者斑块的泛素水平更高(257.4 +/- 118.9 ng / mg vs 110 +/- 14.4 ng / mg,p <.001),硝基酪氨酸(3.8 +/- 0.55) nmol / pg与1.1 +/- 0.19 nmol / pg,p <.001),p53和p16染色(p <.01)和MMP-9水平(14.6 +/- 2.5 microg / mg与3.2 +/- 0.1 .8 microg / mg,p <.001),胶原蛋白含量较低(21.9 +/- 4.8%vs 7.1 +/- 2.8%,p <.05)和蛋白酶体20S活性较低(24.2 +/- 6.9 pmol / mg对比78.4 +/- 10.3 pmol / mg,p <.001)。结论:我们的数据表明蛋白酶体活性的降低促进了血管细胞的衰老,从而促进了人类动脉粥样硬化的发病机理。

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