Investigation of Lipid Metabolism in Dynamic Progression of Coronary Artery Atherosclerosis of Humans by Time-of-Flight Secondary Ion Mass Spectrometry
Investigation of Lipid Metabolism in Dynamic Progression of Coronary Artery Atherosclerosis of Humans by Time-of-Flight Secondary Ion Mass Spectrometry
复制标题
飞行时间二次离子质谱法研究人类冠状动脉粥样硬化动态进展中的脂质代谢
DOI：
10.1021/acs.analchem.0c04367
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发表时间：
2021-02-15
影响因子：
7.4
通讯作者：
Long，Yi-Tao
中科院分区：
文献类型：
--
作者：
Li，Hao-Wen;Hu，Zhan;Long，Yi-Tao
冠状动脉组织中脂质代谢物的改变是动脉粥样硬化（AS）进展过程中的表型变化。全面了解冠状动脉粥样硬化中脂质代谢产物的时空分布，有助于更深入地了解其病理学和识别疾病进展的潜在生物标志物。采用高空间分辨率、高灵敏度飞行时间二次离子质谱（ToF-SIMS）延迟提取模式，分析AS不同阶段脂质代谢产物的种类、数量和分布变化，并以病区为标准。基于高横向分辨率成像，我们进一步分析了ToF-SIMS数据提取的AS病变组织在不同的疾病进展阶段的亚区域，通过半定量比较，聚类分析（t-随机邻居嵌入和HCA），和KEGG富集。因此，脂质的特点在冠状动脉粥样硬化的详细描述。我们构建了冠状动脉AS脂质的ToF-SIMS质谱数据库。获得了40种在不同病理阶段具有不同模式的特异性脂质代谢产物。化学成像揭示了脂质空间分布的进一步细节。此外，亚油酸和花生四烯酸代谢途径被预测在AS进展中是关键的。
Alterations in lipid metabolites in coronary artery tissues are phenotypic changes in the progression of atherosclerosis (AS). A full picture of the spatiotemporal distribution of lipid metabolites in coronary AS is needed for a deeper understanding of its pathology and the identification of potential biomarkers of disease progression. In this work, the changes in species, quantity, and distribution of lipid metabolites at different stages of AS, which were standardized by the disease areas, were analyzed through the high spatial resolution- and high sensitivity-time-of-flight secondary ion mass spectrometry (ToF-SIMS) under delayed extraction mode. Based on high lateral resolution imaging, we further analyzed the ToF-SIMS data extracted from the subregions of AS lesion tissues at different disease progression stages by semiquantitative comparison, clustering analysis (t-stochastic neighbor embedding and HCA), and KEGG enrichment. Thus, a much-detailed description of lipids’ features in coronary AS was achieved. We constructed a ToF-SIMS mass spectrometry database of coronary AS lipids. 40 specific lipid metabolites with distinctive patterns between different pathological stages were obtained. Chemical imaging unveiled further details regarding the spatial distribution of lipids. Moreover, linoleic acid and arachidonic acid metabolic pathway were predicted to be critical in AS progression.