大规模定量代谢组学和质谱成像确定了人类急性A型主动脉夹层的代谢图谱
Large-scale quantitative metabolomics and mass spectrometry imaging define the metabolic atlas in human acute type A aortic dissection.
摘要(中文译文)
急性A型主动脉夹层（ATAAD）是最常见的急性主动脉疾病，死亡率高。迄今为止，人ATAAD升主动脉的全面代谢特征仍未阐明。我们采用大规模靶向代谢组学方法，对取自ATAAD患者、升主动脉胸主动脉瘤（ATAA）患者及健康供体的升主动脉组织进行定量分析，检测了1，349种代谢物。通过整合转录组学和质谱成像（MSI）分析，我们进一步可视化了ATAAD关键代谢网络的空间分布。定量分析揭示了ATAAD患者（n=20）升主动脉中独特的亲水性代谢物和甘油磷脂谱，与ATAA患者（n=20）和健康对照（n=20）存在显著差异。研究发现，嘌呤、嘧啶和氨基酸代谢通路中的多种代谢物在ATAAD升主动脉中发生特异且显著的改变。MSI分析表明，这些差异化代谢物主要富集于中膜和内膜。我们选取了两种ATAAD关键差异代谢物——次黄嘌呤和焦谷氨酸——作为概念验证候选物。在一个前瞻性ATAAD队列（n=196）中，这两种代谢物的循环水平均与不良临床结局呈正相关。功能研究证实，它们通过损害血管平滑肌和内皮细胞功能促进主动脉夹层。本研究首次呈现了人ATAAD升主动脉的大规模定量和空间代谢图谱，揭示了关键代谢紊乱，有望成为急性主动脉疾病的风险标志物和治疗靶点。本研究由慢性非传染性疾病国家科技重大专项和北京市自然科学基金资助。
Abstract
Acute type A aortic dissection (ATAAD) is the most frequent acute aortic disease with high mortality. To date, a comprehensive metabolic characterization of the human ATAAD ascending aorta remains elusive. We used large-scale targeted metabolomics on ascending aortas obtained from patients with ATAAD, patients with ascending thoracic aortic aneurysm (ATAA), and healthy donors to quantify the 1,349 metabolites. By integrating with transcriptomics and mass spectrometry imaging (MSI) analysis, we further visualized the spatial distribution of the key ATAAD-altered metabolic network. Quantitative profiling revealed distinct hydrophilic metabolite and glycerophospholipid profiles in ascending aortas from patients with ATAAD (n = 20), which remarkably differed from those in patients with ATAA (n = 20) and healthy controls (n = 20). Various metabolites in purine, pyrimidine, and amino acid metabolic pathways were found to be specifically and significantly altered in the ascending aorta of ATAAD. MSI analysis indicated that those differentiated metabolites were mainly enriched in the tunica media and intima. Two key ATAAD-altered metabolites-hypoxanthine and pyroglutamic acid-were selected as proof-of-concept candidates. In a prospective ATAAD cohort (n = 196), circulating levels of both metabolites correlated positively with adverse clinical outcomes. Functional studies confirmed they promote aortic dissection by impairing vascular smooth muscle and endothelial cell functions. Our study presents the first large-scale quantitative and spatial metabolic atlas of the human ATAAD ascending aorta, highlighting key metabolic disturbances with potential as risk markers and therapeutic targets for acute aortic diseases. This work was supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project and the Beijing Natural Science Foundation.
如何引用
AMA
Xiaozheng Zhou, Peirong Lin, Ying Ma, Yanru Duan, Lin Zheng, Jiyuan Luo, et al. Large-scale quantitative metabolomics and mass spectrometry imaging define the metabolic atlas in human acute type A aortic dissection.. Med (New York, N.Y.). 2026; doi:10.1016/j.medj.2026.101078.
APA
Xiaozheng Zhou, Peirong Lin, Ying Ma, Yanru Duan, Lin Zheng, Jiyuan Luo, et al (2026). Large-scale quantitative metabolomics and mass spectrometry imaging define the metabolic atlas in human acute type A aortic dissection.. Med (New York, N.Y.). https://doi.org/10.1016/j.medj.2026.101078
GB/T 7714
Xiaozheng Zhou, Peirong Lin, Ying Ma, Yanru Duan, Lin Zheng, Jiyuan Luo, et al. Large-scale quantitative metabolomics and mass spectrometry imaging define the metabolic atlas in human acute type A aortic dissection.[J]. Med (New York, N.Y.), 2026 doi:10.1016/j.medj.2026.101078.
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