TY - JOUR
T1 - Imaging mass spectroscopy delineates the thinned and thickened walls of intracranial aneurysms
AU - Ikedo, Taichi
AU - Minami, Manabu
AU - Kataoka, Hiroharu
AU - Hayashi, Kosuke
AU - Nagata, Manabu
AU - Fujikawa, Risako
AU - Yamazaki, Fumiyoshi
AU - Setou, Mitsutoshi
AU - Yokode, Masayuki
AU - Miyamoto, Susumu
N1 - Funding Information:
This work was supported in part by the Japan Society for the Promotion of Science JSPS KAKENHI [grant numbers 23590361 and 26460338 (to MM), 15K08230 (to MY), and 15H04952 (to HK)]; the Ministry of Education, Culture, Sports, Science and Technology [grant number 15H05898B1 (to MS)]; project for Creation of Research Platforms and Sharing of Advanced Research Infrastructure [grant number 25801 (to MS)]; and CREST from Japan Agency for Medical Research and Development , AMED [grant number 921910520 (to MS)].
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Object The wall thickness of intracranial aneurysms (IAs) is heterogeneous. Although thinning of the IA wall is thought to contribute to IA rupture, the underlying mechanism remains poorly understood. Recently, imaging mass spectroscopy (IMS) has been used to reveal the distribution of phospholipids in vascular diseases. To investigate the feature of phospholipid composition of IA walls, we conducted IMS in a rat model of experimentally induced IA. Material and methods IAs were surgically induced in 7-week-old male rats and analyzed by IMS in negative-ion mode. Results A molecule at m/z 885.5 was more abundant in the thickened wall than in the thinned wall (P = 0.03). Multiple-stage mass spectroscopy revealed the molecule to be phosphatidylinositol containing stearic acid and arachidonic acid (PI 18:0/20:4). Immunohistochemistry indicated that vascular smooth muscle cells (SMCs) in the thickened wall had dedifferentiated phenotypes. To investigate the relationship between accumulation of PI (18:0/20:4) and phenotypic changes in SMCs, we subjected primary mouse aortic SMCs to liquid chromatography–tandem mass spectrometry. Notably, dedifferentiated SMCs had 1.3-fold more PI (18:0/20:4) than partly differentiated SMCs. Conclusions Our study demonstrated the heterogeneity in phospholipid composition of the aneurysmal walls using experimentally induced IAs. PI (18:0/20:4) accumulated at high levels in the thickened aneurysmal wall where synthetic dedifferentiated SMCs exist, suggesting that this phospholipid may be involved in the phenotypic switching of medial SMCs in the IA wall.
AB - Object The wall thickness of intracranial aneurysms (IAs) is heterogeneous. Although thinning of the IA wall is thought to contribute to IA rupture, the underlying mechanism remains poorly understood. Recently, imaging mass spectroscopy (IMS) has been used to reveal the distribution of phospholipids in vascular diseases. To investigate the feature of phospholipid composition of IA walls, we conducted IMS in a rat model of experimentally induced IA. Material and methods IAs were surgically induced in 7-week-old male rats and analyzed by IMS in negative-ion mode. Results A molecule at m/z 885.5 was more abundant in the thickened wall than in the thinned wall (P = 0.03). Multiple-stage mass spectroscopy revealed the molecule to be phosphatidylinositol containing stearic acid and arachidonic acid (PI 18:0/20:4). Immunohistochemistry indicated that vascular smooth muscle cells (SMCs) in the thickened wall had dedifferentiated phenotypes. To investigate the relationship between accumulation of PI (18:0/20:4) and phenotypic changes in SMCs, we subjected primary mouse aortic SMCs to liquid chromatography–tandem mass spectrometry. Notably, dedifferentiated SMCs had 1.3-fold more PI (18:0/20:4) than partly differentiated SMCs. Conclusions Our study demonstrated the heterogeneity in phospholipid composition of the aneurysmal walls using experimentally induced IAs. PI (18:0/20:4) accumulated at high levels in the thickened aneurysmal wall where synthetic dedifferentiated SMCs exist, suggesting that this phospholipid may be involved in the phenotypic switching of medial SMCs in the IA wall.
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U2 - 10.1016/j.bbrc.2017.10.133
DO - 10.1016/j.bbrc.2017.10.133
M3 - Article
C2 - 29111330
AN - SCOPUS:85033365204
VL - 495
SP - 332
EP - 338
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -