Age-associated proteomic alterations in human aortic media
Age-associated proteomic alterations in human aortic media
复制标题
人类主动脉中膜中与年龄相关的蛋白质组改变
DOI：
10.1111/ggi.13757
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发表时间：
2019
影响因子：
3.3
通讯作者：
Sawabe M.
中科院分区：
文献类型：
--
作者：
Miura Y.;Tsumoto H.;Iwamoto M.;Yamaguchi Y.;Ko P.;Soejima Y.;Yoshida S.;Toda T.;Arai T.;Hamamatsu A.;Endo T.;Sawabe M.
人类血管衰老主要发生在介质中，目前尚未完全了解。在这里，我们使用蛋白质组学方法来研究人类主动脉介质中与年龄相关的变化，目的是了解血管衰老的分子机制。方法收集老年人（70-100岁，n= 25）、中年人（49-68岁，n= 24）和年轻人（21-39岁，n= 12）的主动脉介质冷冻标本。我们使用两种蛋白质组学技术，二维差异凝胶电泳和等压标签进行相对和绝对定量，并对不同年龄组的差异表达蛋白进行免疫组织化学分析。结果蛋白质组学分析显示，老年人主动脉介质中产生内啡肽的乳酸粘附素的表达升高。免疫组织化学和刚果红染色显示乳粘蛋白和载脂蛋白E沉积，老年主动脉介质淀粉样变增强。此外，氧化损伤标志物（8 -羟基- 2' -脱氧鸟苷和4 -羟基- 2 -壬烯醛）在中老年个体的主动脉介质中显著升高。抗氧化蛋白（硫氧还蛋白和细胞外超氧化物歧化酶）的免疫组织化学表达在中老年组也很高。氧化损伤可能引起平滑肌细胞的破坏，导致平滑肌细胞中α -肌动蛋白（一种高表达蛋白）的减少和基质重塑，其中一些与细胞外基质相关的蛋白随着年龄的增长而改变。结论蛋白质组学方法表明，乳酸粘附素的表达升高可能与老年主动脉介质中淀粉样蛋白沉积、氧化应激增强、抗氧化蛋白诱导和基质重塑有关。Geriatr Gerontol Int 2019；19日:1054 - 1062。
AimHuman vascular senescence, which mainly occurs in media, is not completely understood. Here, we used proteomic approaches to investigate age‐associated changes in human aortic media with the goal of understanding the molecular mechanisms underlying vascular senescence.MethodCryopreserved autopsy samples of aortic media from older‐aged (aged 70–100 years,n= 25), middle‐aged (aged 49–68 years,n= 24), and young (aged 21–39 years,n= 12) subjects were collected. We used two proteomic techniques, two‐dimensional differential gel electrophoresis and isobaric tags for relative and absolute quantitation, and we subjected differentially‐expressed proteins among age groups to immunohistochemical analyses.ResultsProteomic analyses showed that the expression of lactadherin, which produces medin, was elevated in aortic media of older‐aged individuals. Immunohistochemical and Congo red staining showed that lactadherin and apolipoprotein E were deposited, and that amyloidosis was enhanced in older‐aged aortic media. Furthermore, the markers of oxidative damage (8‐hydroxy‐2'‐deoxyguanosine and 4‐hydroxy‐2‐nonenal) were significantly elevated in aortic media of middle‐aged or older‐aged individuals. The immunohistochemical expression of anti‐oxidant proteins (thioredoxin and extracellular superoxide dismutase) was also high in middle‐aged and older‐aged groups. Oxidative damage might induce the disruption of smooth muscle cells, resulting in the decrement of α‐actin, a highly‐expressed protein in smooth muscle cells, and matrix remodeling, in which several proteins associated with extracellular matrix were altered with aging.ConclusionsProteomic approaches showed that the elevated expression of lactadherin might contribute to amyloid deposition, enhancement of oxidative stress, induction of antioxidant proteins and matrix remodeling in older‐aged aortic media.Geriatr Gerontol Int 2019; 19: 1054–1062.