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

Slijkhuis, Nuria; Razzi, F.; Korteland, Suze Anne; Heijs, Bram; van Gaalen, Kim; Duncker, Dirk J.; van der Steen, A.F.W.; van Steijn, V.; van Beusekom, Heleen M.M.; van Soest, G.

doi:10.1016/j.jlr.2024.100504

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

Title

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

Author

Slijkhuis, Nuria (Erasmus MC)
Razzi, F. (TU Delft ChemE/Product and Process Engineering; Erasmus MC)
Korteland, Suze Anne (Erasmus MC)
Heijs, Bram (Leiden University Medical Center)
van Gaalen, Kim (Erasmus MC)
Duncker, Dirk J. (Erasmus MC)
van der Steen, A.F.W. (TU Delft ImPhys/Medical Imaging; TU Delft ImPhys/Verweij group; Erasmus MC; Chinese Academy of Sciences)
van Steijn, V. (TU Delft ChemE/Product and Process Engineering)
van Beusekom, Heleen M.M. (Erasmus MC)
van Soest, G. (TU Delft Biomechanical Engineering; Massachusetts General Hospital; Erasmus MC)

Department

Biomechanical Engineering

Date

2024

Abstract

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 ¼ 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 ¼ 6), mild (n ¼ 6), and advanced disease (n ¼ 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 ceramidephosphoethanolamine(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.

Subject

Atherosclerosis
dyslipidemias
familial hypercholesterolemia
histology
inflammation
lipids
lipids/chemistry
mass spectrometry imaging
plaque progression
vascular biology