TY - JOUR
T1 - Identification and visualization of oxidized lipids in atherosclerotic plaques by microscopic imaging mass spectrometry-based metabolomics
AU - Shen, Lianhua
AU - Yamamoto, Takushi
AU - Tan, Xian Wen
AU - Ogata, Koretsugu
AU - Ando, Eiji
AU - Ozeki, Eiichi
AU - Matsuura, Eiji
N1 - Funding Information:
This research was supported in part by a grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan; KAKEN ( Japan Society for the Promotion of Science [JSPS] ), Grant Number: 26253036 .
Funding Information:
This research was supported in part by a grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan; KAKEN (Japan Society for the Promotion of Science [JSPS]), Grant Number: 26253036.
Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/10
Y1 - 2020/10
N2 - Background and aims: Dysregulated lipid metabolism has emerged as one of the major risk factors of atherosclerosis. Presently, there is a consensus that oxidized LDL (oxLDL) promotes development of atherosclerosis and downstream chronic inflammatory responses. Due to the dynamic metabolic disposition of lipoprotein, conventional approach to purify bioactive lipids for subsequent comprehensive analysis has proven to be inadequate for elucidation of the oxidized lipids species accountable for pathophysiology of atherosclerotic lesions. Herein, we aimed to utilize a novel mass microscopic imaging technology, coupled with mass spectrometry (MS) to characterize oxidized lipids in atherosclerotic lesions. Methods: We attempted to use MALDI-TOF-MS and iMScope to identify selected oxidized lipid targets and visualize their respective localizations in study models of atherosclerosis. Results: Based on the MS analysis, detection of 7-K under positive ionization through product ion peak at m/z 383 [M + H–H2O] indicated the distinctive presence of targeted lipid within Cu2+-oxLDL and Cu2+-oxLDL loaded macrophage-like J774A.1 cells, along with other cholesterol oxidation products. Moreover, the application of two-dimensional iMScope has successfully visualized the localization of lipids in aortic atherosclerotic plaques of the Watanabe heritable hyperlipidemic (WHHL) rabbit. Distinctive lipid distribution profiles were observed in atherosclerotic lesions of different sizes, especially the localizations of lysoPCs in atherosclerotic plaques. Conclusions: Taken together, we believe that both MALDI-TOF-MS and iMScope metabolomics technology may offer a novel proposition for future pathophysiological studies of lipid metabolism in atherosclerosis.
AB - Background and aims: Dysregulated lipid metabolism has emerged as one of the major risk factors of atherosclerosis. Presently, there is a consensus that oxidized LDL (oxLDL) promotes development of atherosclerosis and downstream chronic inflammatory responses. Due to the dynamic metabolic disposition of lipoprotein, conventional approach to purify bioactive lipids for subsequent comprehensive analysis has proven to be inadequate for elucidation of the oxidized lipids species accountable for pathophysiology of atherosclerotic lesions. Herein, we aimed to utilize a novel mass microscopic imaging technology, coupled with mass spectrometry (MS) to characterize oxidized lipids in atherosclerotic lesions. Methods: We attempted to use MALDI-TOF-MS and iMScope to identify selected oxidized lipid targets and visualize their respective localizations in study models of atherosclerosis. Results: Based on the MS analysis, detection of 7-K under positive ionization through product ion peak at m/z 383 [M + H–H2O] indicated the distinctive presence of targeted lipid within Cu2+-oxLDL and Cu2+-oxLDL loaded macrophage-like J774A.1 cells, along with other cholesterol oxidation products. Moreover, the application of two-dimensional iMScope has successfully visualized the localization of lipids in aortic atherosclerotic plaques of the Watanabe heritable hyperlipidemic (WHHL) rabbit. Distinctive lipid distribution profiles were observed in atherosclerotic lesions of different sizes, especially the localizations of lysoPCs in atherosclerotic plaques. Conclusions: Taken together, we believe that both MALDI-TOF-MS and iMScope metabolomics technology may offer a novel proposition for future pathophysiological studies of lipid metabolism in atherosclerosis.
KW - Atherosclerosis
KW - Imaging mass microscopy (iMScope)
KW - Low-density lipoprotein (LDL)
KW - Mass spectroscopy (MS)
KW - Oxidized LDL (oxLDL)
KW - Oxidized lipids
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U2 - 10.1016/j.atherosclerosis.2020.08.001
DO - 10.1016/j.atherosclerosis.2020.08.001
M3 - Article
C2 - 32911376
AN - SCOPUS:85090277987
VL - 311
SP - 1
EP - 12
JO - Atherosclerosis
JF - Atherosclerosis
SN - 0021-9150
ER -