Lipid signature of advanced human carotid atherosclerosis assessed by mass spectrometry imaging

Journal of Lipid Research

Frank J.H. Gijsen¹  Bram Heijs²  Gijs Van Soest³  Antonius F.W. Van der Steen³  Kim Van der Heiden³  Astrid M. Moerman³  Mirjam Visscher³  Kim Van Gaalen³  Nuria Slijkhuis³  Theo Klein⁴  Yolanda B. De Rijke⁴  Heleen M.M. Van Beusekom⁵  Peter C. Burgers⁶  Theo M. Luider⁶  Hence J.M. Verhagen⁷ 

[1] Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China;Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands;Department of Cardiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands;Department of Clinical Chemistry, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands;Department of Experimental Cardiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands;Department of Neurology, Laboratory of Neuro-Oncology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands;Department of Vascular and Endovascular Surgery, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands;

关键词: atherosclerosis;    mass spectrometry;    lipidomics;    lipids;    sphingolipids;    Vascular Biology;   

DOI  :  

来源: DOAJ

【 摘 要 】

Abstract: Carotid atherosclerosis is a risk factor for ischemic stroke, one of the main causes of mortality and disability worldwide. The disease is characterized by plaques, heterogeneous deposits of lipids, and necrotic debris in the vascular wall, which grow gradually and may remain asymptomatic for decades. However, at some point a plaque can evolve to a high-risk plaque phenotype, which may trigger a cerebrovascular event. Lipids play a key role in the development and progression of atherosclerosis, but the nature of their involvement is not fully understood. Using matrix-assisted laser desorption/ionization mass spectrometry imaging, we visualized the distribution of approximately 200 different lipid signals, originating of >90 uniquely assigned species, in 106 tissue sections of 12 human carotid atherosclerotic plaques. We performed unsupervised classification of the mass spectrometry dataset, as well as a histology-directed multivariate analysis. These data allowed us to extract the spatial lipid patterns associated with morphological plaque features in advanced plaques from a symptomatic population, revealing spatial lipid patterns in atherosclerosis and their relation to histological tissue type. The abundances of sphingomyelin and oxidized cholesteryl ester species were elevated specifically in necrotic intima areas, whereas diacylglycerols and triacylglycerols were spatially correlated to areas containing the coagulation protein fibrin. These results demonstrate a clear colocalization between plaque features and specific lipid classes, as well as individual lipid species in high-risk atherosclerotic plaques.

【 授权许可】

Unknown