Abdominal aortic aneurysm (AAA) is a common but life-threatening vascular condition in men at an advanced age. However, the underlying mechanisms of age-increased incidence and mortality of AAA remain elusive. Here, we performed RNA sequencing (RNA-seq) of mouse aortas from males (young: 3-month, n = 4 vs old: 23-month, n = 4) and integrated with the data sets of human aortas (young: 20–39, n = 47 vs old: 60–79 years, n = 92) from GTEx project and the data set (GSE183464) for AAA to search for age-shifted aortic aneurysm genes, their relevant biological processes, and signaling pathways. Angiotensin II-induced AAA in mice was used to verify the critical findings. We found 1 001 genes transcriptionally changed with ages in both mouse and human. Most age-increased genes were enriched intracellularly and the relevant biological processes included mitochondrial function and translational controls, whereas the age-decreased genes were largely localized in extracellular regions and cell periphery and the involved biological processes were associated with extracellular matrix (ECM). Fifty-one were known genes for AAA and found dominantly in extracellular region. The common age-shifted vascular genes and known aortic aneurysm genes had shared functional influences on ECM organization, apoptosis, and angiogenesis. Aorta with angiotensin II-induced AAA exhibited similar phenotypic changes in ECM to that in old mice. Together, we present a conserved transcriptional signature for aortic aging and provide evidence that mitochondrial dysfunction and the imbalanced ribosomal homeostasis act likely as driven-forces for aortic aging and age-disturbed ECM is the substrate for developing AAA.

中文翻译：

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年龄紊乱的血管细胞外基质与腹主动脉瘤有关


腹主动脉瘤（AAA）是老年男性常见但危及生命的血管疾病。然而，随着年龄的增长，AAA 发病率和死亡率增加的根本机制仍然难以捉摸。在这里，我们对雄性小鼠主动脉（年轻：3 个月，n = 4 vs 年老：23 个月，n = 4）进行了 RNA 测序 (RNA-seq)，并与人类主动脉数据集（年轻：20 –39，n = 47 与老年：60-79 岁，n = 92）来自 GTEx 项目和 AAA 数据集 (GSE183464)，用于搜索年龄转移主动脉瘤基因、其相关生物过程和信号通路。使用血管紧张素 II 诱导的小鼠 AAA 来验证这一重要发现。我们发现小鼠和人类中有 1001 个基因随着年龄的增长而发生转录变化。大多数年龄增加的基因在细胞内富集，相关的生物过程包括线粒体功能和翻译控制，而年龄减少的基因主要集中在细胞外区域和细胞外周，所涉及的生物过程与细胞外基质（ECM）相关。 51 个已知的 AAA 基因主要存在于细胞外区域。常见的年龄转移血管基因和已知的主动脉瘤基因对 ECM 组织、细胞凋亡和血管生成具有共同的功能影响。血管紧张素 II 诱导的 AAA 的主动脉在 ECM 中表现出与老年小鼠相似的表型变化。我们共同提出了主动脉衰老的保守转录特征，并提供证据证明线粒体功能障碍和核糖体稳态失衡可能是主动脉衰老的驱动力，而年龄干扰的 ECM 是发生 AAA 的基础。