Spatial lipidomics of coronary atherosclerotic plaque development in a familial hypercholesterolemia swine model.

Autor:	Slijkhuis N; Department of Cardiology, Cardiovascular Institute, Thorax Center, Erasmus MC, Rotterdam, The Netherlands., Razzi F; Department of Experimental Cardiology, Cardiovascular Institute, Thorax Center, Erasmus MC, Rotterdam, The Netherlands; Department of Chemical Engineering, Delft University of Technology, Delft, The Netherlands., Korteland SA; Department of Cardiology, Cardiovascular Institute, Thorax Center, Erasmus MC, Rotterdam, The Netherlands., Heijs B; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands., van Gaalen K; Department of Cardiology, Cardiovascular Institute, Thorax Center, Erasmus MC, Rotterdam, The Netherlands., Duncker DJ; Department of Experimental Cardiology, Cardiovascular Institute, Thorax Center, Erasmus MC, Rotterdam, The Netherlands., van der Steen AFW; Department of Cardiology, Cardiovascular Institute, Thorax Center, Erasmus MC, Rotterdam, The Netherlands; Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China; Department of Imaging Science and Technology, Delft University of Technology, Delft, The Netherlands., van Steijn V; Department of Chemical Engineering, Delft University of Technology, Delft, The Netherlands., van Beusekom HMM; Department of Experimental Cardiology, Cardiovascular Institute, Thorax Center, Erasmus MC, Rotterdam, The Netherlands., van Soest G; Department of Cardiology, Cardiovascular Institute, Thorax Center, Erasmus MC, Rotterdam, The Netherlands; Department of Precision and Microsystems Engineering, Delft University of Technology, Delft, The Netherlands; Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA. Electronic address: g.vansoest@erasmusmc.nl.
Jazyk:	angličtina
Zdroj:	Journal of lipid research [J Lipid Res] 2024 Feb; Vol. 65 (2), pp. 100504. Date of Electronic Publication: 2024 Jan 19.
DOI:	10.1016/j.jlr.2024.100504
Abstrakt:	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. Competing Interests: Conflict of interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gijs van Soest is an advisor to, and has a financial interest in, Kaminari Medical BV. The other authors have no conflicts of interest to declare. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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