Identifying lipid traces of atherogenic mechanisms in human carotid plaque

Identifying lipid traces of atherogenic mechanisms in human carotid plaque

Slijkhuis, Nuria (Erasmus MC)
Mirzaian, Mina (Erasmus MC)
Korteland, Suze Anne (Erasmus MC)
Heijs, Bram (Leiden University Medical Center)
van Gaalen, Kim (Erasmus MC)
Nieuwenhuizen, Ingeborg (Erasmus MC)
van der Heiden, Kim (Erasmus MC)
Claude, Emmanuelle (Waters Corporation)
van Soest, G. (TU Delft Biomechanical Engineering; Erasmus MC)

Biomechanical Engineering

2023

Background and aims: Lipids play an important role in atherosclerotic plaque development and are interesting candidate predictive biomarkers. However, the link between circulating lipids, accumulating lipids in the vessel wall, and plaque destabilization processes in humans remains largely unknown. This study aims to provide new insights into the role of lipids in atherosclerosis using lipidomics and mass spectrometry imaging to investigate lipid signatures in advanced human carotid plaque and plasma samples. Methods: We used lipidomics and desorption electrospray ionization mass spectrometry imaging (DESI-MSI) to investigate lipid signatures of advanced human carotid plaque and plasma obtained from patients who underwent carotid endarterectomy (n = 14 out of 17 whose plaque samples were analyzed by DESI-MSI). Multivariate data analysis and unsupervised clustering were applied to identify lipids that were the most discriminative species between different patterns in plaque and plasma. These patterns were interpreted by quantitative comparison with conventional histology. Results: Lipidomics detected more than 300 lipid species in plasma and plaque, with markedly different relative abundances. DESI-MSI visualized the spatial distribution of 611 lipid-related m/z features in plaques, of which 330 m/z features could be assigned based on exact mass, comparison to the lipidomic data, and high mass resolution MSI. Matching spatial lipid patterns to histological areas of interest revealed several molecular species that were colocalized with pertinent disease processes in plaque including specific sphingomyelin and ceramide species with calcification, phospholipids and free fatty acids with inflammation, and triacylglycerols and phosphatidylinositols with fibrin-rich areas. Conclusions: By comparing lipid species in plaque and plasma, we identified those circulating species that were also prominently present in plaque. Quantitative comparison of lipid spectral patterns with histology revealed the presence of specific lipid species in destabilized plaque areas, corroborating previous in vitro and animal studies.

Atherosclerosis
Carotid endarterectomy
Desorption electrospray ionization-mass spectrometry imaging
Histology
Lipidomics
Plaque destabilization

http://resolver.tudelft.nl/uuid:88108b16-24b2-42f3-9bdc-be5cbfc4aaff

https://doi.org/10.1016/j.atherosclerosis.2023.117340

0021-9150

Atherosclerosis, 385

Institutional Repository

journal article

© 2023 Nuria Slijkhuis, Mina Mirzaian, Suze Anne Korteland, Bram Heijs, Kim van Gaalen, Ingeborg Nieuwenhuizen, Kim van der Heiden, Emmanuelle Claude, G. van Soest, More Authors