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In vivo isotopically labeled atherosclerotic aorta plaques in ApoE KO mice and molecular profiling by matrix‐assisted laser desorption/ionization mass spectrometric imaging
Author(s) -
CastroPerez Jose,
Hatcher Nathan,
Kofi Karikari Nana,
Wang ShengPing,
Mendoza Vivienne,
Shion Henry,
Millar Alan,
Shockcor John,
Towers Mark,
McLaren David,
Shah Vinit,
Previs Stephen,
Akinsanya Karen,
Cleary Michele,
Roddy Thomas P.,
Johns Douglas G.
Publication year - 2014
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.7039
Subject(s) - chemistry , mass spectrometry imaging , aorta , cholesterol , matrix assisted laser desorption/ionization , maldi imaging , in vivo , mass spectrometry , biophysics , pathology , desorption , medicine , biochemistry , chromatography , organic chemistry , adsorption , microbiology and biotechnology , biology
RATIONALE The ability to quantify rates of formation, regression and/or remodeling of atherosclerotic plaque should facilitate a better understanding of the pathogenesis and management of cardiovascular disease. In the current study, we coupled a stable isotope labeled tracer protocol with matrix‐assisted laser desorption/ionization mass spectrometry imaging (MALDI‐MSI) to examine spatial and temporal lipid dynamics in atherosclerotic plaque. METHODS To promote plaque formation in the aorta region, ApoE KO mice were fed a high cholesterol diet (0.15% cholesterol) and orally dosed with (2,2,3,4,4,6‐d 6 )‐cholesterol over several weeks. Tissue sections of ~10 µm thickness were analyzed by MALDI‐MSI using matrix deposition by either chemical sublimation or acoustic droplet ejection. RESULTS MALDI‐MSI yielded distinct spatial distribution information for a variety of lipid classes including specific lysophosphatidylcholines typically associated with atherosclerosis‐related tissue damage such as phospholipase 2 (Lp‐PLA 2 ) that mediate chemotactic responses to inflammation (e.g. LPC 16:0, LPC 18:0 and LPC 18:1) as well as free cholesterol and cholesteryl esters that contribute to atheroma formation. MALDI mass spectra acquired from aorta tissue sections clearly distinguished non‐esterified and esterified versions of (2,2,3,4,4,6‐d 6 )‐cholesterol within aortic plaque regions and showed distinct spatial accumulation of the cholesterol tracer. CONCLUSIONS The ability to couple stable isotope based protocols with MALDI‐MSI enables a novel strategy to characterize the effects of therapeutic treatments on atherosclerotic plaque formation, regression and potential remodeling of the complex lipid components with high chemical specificity and spatiotemporal information. Copyright © 2014 John Wiley & Sons, Ltd.