Coronary atherosclerosis is caused by plaque build-up, with lipids playing a pivotal role in its progression. However, lipid composition and distribution within coronary atherosclerosis remain unknown. This study aims to characterize lipids and investigate differences in lipid composition across disease stages to aid in the understanding of disease progression. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) was used to visualize lipid distributions in coronary artery sections (n=17) from hypercholesterolemic swine. We performed histology on consecutive sections to classify the artery segments and to investigate colocalization between lipids and histological regions of interest in advanced plaque, including necrotic core and inflammatory cells. Segments were classified as healthy (n=6), mild (n=6), and advanced disease (n=5) artery segments. Multivariate data analysis was employed to find differences in lipid composition between the segment types, and the lipids' spatial distribution was investigated using non-negative matrix factorization (NMF). Through this process, MALDI-MSI detected 473 lipid-related features. NMF clustering described three components in positive ionization mode: triacylglycerides (TAG), phosphatidylcholines (PC), and cholesterol species. In negative ionization mode, two components were identified: one driven by phosphatidylinositol(PI)(38:4), and one driven by ceramide-phosphoethanolamine(36:1). Multivariate data analysis showed the association between advanced disease and specific lipid signatures like PC(O-40:5) and cholesterylester(CE)(18:2). Ether-linked phospholipids and LysoPC species were found to colocalize with necrotic core, and mostly CE, ceramide, and PI species colocalized with inflammatory cells. This study, therefore, uncovers distinct lipid signatures correlated with plaque development and their colocalization with necrotic core and inflammatory cells, enhancing our understanding of coronary atherosclerosis progression.

中文翻译：

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家族性高胆固醇血症猪模型中冠状动脉粥样硬化斑块发展的空间脂质组学。

冠状动脉粥样硬化是由斑块积聚引起的，脂质在其进展中起着关键作用。然而，冠状动脉粥样硬化内的脂质成分和分布仍然未知。本研究旨在表征脂质并研究不同疾病阶段脂质成分的差异，以帮助了解疾病进展。使用基质辅助激光解吸/电离质谱成像 (MALDI-MSI) 来可视化高胆固醇血症猪冠状动脉切片 (n=17) 中的脂质分布。我们对连续切片进行组织学分析，对动脉节段进行分类，并研究晚期斑块中脂质与感兴趣的组织学区域（包括坏死核心和炎症细胞）之间的共定位。动脉段被分为健康 (n=6)、轻度 (n=6) 和晚期疾病 (n=5) 动脉段。采用多变量数据分析来发现片段类型之间脂质组成的差异，并使用非负矩阵分解（NMF）研究脂质的空间分布。通过这个过程，MALDI-MSI 检测到了 473 个脂质相关特征。NMF 聚类描述了正电离模式下的三种成分：三酰基甘油酯 (TAG)、磷脂酰胆碱 (PC) 和胆固醇种类。在负电离模式下，鉴定出两种成分：一种由磷脂酰肌醇（PI）（38:4）驱动，另一种由神经酰胺-磷酸乙醇胺（36:1）驱动。多变量数据分析显示晚期疾病与特定脂质特征（如 PC(O-40:5) 和胆固醇 (CE)(18:2)）之间的关联。发现醚连接的磷脂和 LysoPC 物种与坏死核心共定位，并且大多数 CE、神经酰胺和 PI 物种与炎症细胞共定位。因此，这项研究揭示了与斑块形成及其与坏死核心和炎症细胞共定位相关的独特脂质特征，增强了我们对冠状动脉粥样硬化进展的理解。