TY - JOUR
T1 - Spatial lipidomics of coronary atherosclerotic plaque development in a familial hypercholesterolemia swine model
AU - Slijkhuis, Nuria
AU - Razzi, Francesca
AU - Korteland, Suze Anne
AU - Heijs, Bram
AU - van Gaalen, Kim
AU - Duncker, Dirk J.
AU - van der Steen, Antonius F.W.
AU - van Steijn, Volkert
AU - van Beusekom, Heleen M.M.
AU - van Soest, Gijs
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - Atherosclerosis
KW - dyslipidemias
KW - familial hypercholesterolemia
KW - histology
KW - inflammation
KW - lipids
KW - lipids/chemistry
KW - mass spectrometry imaging
KW - plaque progression
KW - vascular biology
UR - http://www.scopus.com/inward/record.url?scp=85185837618&partnerID=8YFLogxK
U2 - 10.1016/j.jlr.2024.100504
DO - 10.1016/j.jlr.2024.100504
M3 - Article
C2 - 38246237
AN - SCOPUS:85185837618
SN - 0022-2275
VL - 65
JO - Journal of Lipid Research
JF - Journal of Lipid Research
IS - 2
M1 - 100504
ER -