title: Imaging mass spectrometry-based histopathologic examination of atherosclerotic lesions.
abstract: OBJECTIVE
  Imaging mass spectrometry (IMS) enables the visualization of individual molecules present on tissue sections. We attempted to identify and visualize specific markers for aortic atherosclerotic lesions.
  
  
  RESULTS
  Atherosclerotic lesions were obtained from aortic roots of apolipoprotein E (ApoE)-deficient mice at 60 weeks of age and from femoral arteries of humans with peripheral artery occlusive disease. IMS was performed with a matrix-assisted laser desorption/ionization mass spectrometry time-of-flight (TOF)/TOF-type instrument. The molecular ions at m/z 671.6 and 673.6 were found to be specific molecules in the mouse and human lipid-rich regions. These molecules were assigned as cholesterol linoleate (CE 18:2) and cholesterol oleate (CE 18:1). In the case of the human samples, triacylglycerol was also localized in the lipid-rich regions. The distributions of the molecular ions at m/z 804.5 and 832.5 were the same as the distribution of both the mouse and the human SMCs. These molecules were assigned as phosphatidylcholine (PC) (diacyl 16:0/20:4) and PC (diacyl 18:0/20:4). The molecular ion at m/z 566.9 was localized in the mouse calcified regions, and the molecular ions at m/z 539.0 were localized in the human calcified regions.
  
  
  CONCLUSIONS
  The IMS-based histopathologic examination (IbHE) revealed the characteristic peaks of lipid-rich regions, SMCs, and calcified regions in the atherosclerotic lesions. In addition, IbHE revealed the characteristic distribution of lipids in human atherosclerotic lesions. These data indicate that an IMS-based pathologic approach is of considerable value as a new histopathologic examination.
authors.affiliation: Department of Cell Biology and Anatomy, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan. zaimanobuhiro@gmail.com
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Zaima
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sasaki
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Xian Wu
authors.initials: XW
authors.lastname: Cheng
authors.forename: Kenji
authors.initials: K
authors.lastname: Onoue
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hayasaka
authors.forename: Naoko
authors.initials: N
authors.lastname: Goto-Inoue
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Enomoto
authors.forename: Naoki
authors.initials: N
authors.lastname: Unno
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kuzuya
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Setou
mesh_terms: D000818:Animals; D001018:Aortic Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002114:Calcinosis / Q000378:metabolism / Q000473:pathology; D002788:Cholesterol Esters / Q000032:analysis; D004195:Disease Models, Animal; D006801:Humans; D008041:Linoleic Acids / Q000032:analysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058729:Peripheral Arterial Disease / Q000378:metabolism / Q000473:pathology*; D010713:Phosphatidylcholines / Q000032:analysis; D011237:Predictive Value of Tests; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014280:Triglycerides / Q000032:analysis
chemical_list: D001057:Apolipoproteins E; D002788:Cholesterol Esters; D008041:Linoleic Acids; D010713:Phosphatidylcholines; D014280:Triglycerides; C014409:cholesteryl oleate