Aging Alters the Aortic Proteome in Health and Thoracic Aortic Aneurysm.
Aging Alters the Aortic Proteome in Health and Thoracic Aortic Aneurysm.
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DOI：
10.1161/atvbaha.122.317643
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发表时间：
2022-08
影响因子：
8.7
通讯作者：
Goldstein, Daniel R.
中科院分区：
文献类型：
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作者：
Tyrrell, Daniel J.;Chen, Judy;Li, Benjamin Y.;Wood, Sherri C.;Rosebury-Smith, Wendy;Remmer, Henriette A.;Jiang, Longtan;Zhang, Min;Salmon, Morgan;Ailawadi, Gorav;Yang, Bo;Goldstein, Daniel R.
衰老会增强大多数慢性疾病，但其对健康人体主动脉组织和胸主动脉瘤（TAA）的影响仍不清楚。我们使用了健康标本（n=17）和接受TAA手术修复的标本（n=20）的人类主动脉生物储存库。首先，我们进行了蛋白质组学比较健康捐赠者的乳房和年轻的乳房标本（即，<60岁）和老年人（即，年龄≥ 60岁）受试者。其次，我们通过免疫印迹测量了参与线粒体自噬的蛋白质（即，Parkin），以及尿道诱导的炎症途径，特别是TLR 9、STING和干扰素（IFN）-β。蛋白质组学研究表明，衰老在数量和质量上都改变了主动脉从健康到TAA。而年轻的阿利塔斯表现出丰富的免疫过程，老年阿利塔斯表现出丰富的代谢过程。免疫印迹显示，帕金的表达与健康受试者的年龄直接相关，但与TAA受试者的年龄呈负相关。在TAA中，而不是在健康中，STING的磷酸化和IFN-β的表达受到年龄的影响，无论受试者是否有二尖瓣或三尖瓣。在二尖瓣和TAA受试者中，TLR 9表达与受试者年龄呈正相关。有趣的是，尽管STING的磷酸化与受试者年龄负相关，但IFN-β与受试者年龄正相关。衰老将人类主动脉蛋白质组从健康状态转变为TAA，导致生物过程的差异调节。我们的研究结果表明，缓解血管疾病（包括TAA）的治疗方法的开发可能需要根据受试者的年龄进行修改。
Aging enhances most chronic diseases but its impact on human aortic tissue in health and in thoracic aortic aneurysms (TAA) remains unclear. We employed a human aortic biorepository of healthy specimens (n=17) and those that underwent surgical repair for TAA (n=20). First, we performed proteomics comparing aortas of healthy donors to aneurysmal specimens, in young (i.e., <60 years of age) and old (i.e., ≥ 60 years of age) subjects. Second, we measured proteins, via immunoblotting, involved in mitophagy (i.e., Parkin), and also mitochondrial-induced inflammatory pathways, specifically TLR9, STING, and interferon (IFN)-β. Proteomics revealed that aging transformed the aorta both quantitatively and qualitatively from health to TAA. Whereas young aortas exhibited an enrichment of immunological processes, older aortas exhibited an enrichment of metabolic processes. Immunoblotting revealed that the expression of Parkin directly correlated to subject age in health, but inversely to subject age in TAA. In TAA, but not in health, phosphorylation of STING and the expression of IFN-β was impacted by aging regardless of whether subjects had bicuspid or tricuspid valves. In subjects with bicuspid valves and TAAs, TLR9 expression positively correlated with subject age. Interestingly, whereas phosphorylation of STING was inversely correlated with subject age, IFN-β positively correlated with subject age. Aging transforms the human aortic proteome from health to TAA, leading to a differential regulation of biological processes. Our results suggest that the development of therapies to mitigate vascular diseases including TAA, may need to be modified depending on subject age.
影响因子：
3.8
作者：
Yu B;Zhu HD;Shi XL;Chen PP;Sun XM;Xia GY;Fang M;Zhong YX;Tang XL;Zhang T;Pan HT
通讯作者：
Pan HT