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- Title
In vivo isotopically labeled atherosclerotic aorta plaques in ApoE KO mice and molecular profiling by matrix-assisted laser desorption/ionization mass spectrometric imaging.
- Authors
Castro‐Perez, Jose; Hatcher, Nathan; Kofi Karikari, Nana; Wang, Sheng‐Ping; 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.
- Abstract
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-d6)-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-PLA2) 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-d6)-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.
- Subjects
ATHEROSCLEROTIC plaque; LABORATORY mice; MATRIX-assisted laser desorption-ionization; HIGH cholesterol diet; SPATIAL distribution (Quantum optics); LYSOPHOSPHATIDYLCHOLINE acyltransferase; CHEMOTACTIC factors
- Publication
Rapid Communications in Mass Spectrometry: RCM, 2014, Vol 28, Issue 22, p2471
- ISSN
0951-4198
- Publication type
Article
- DOI
10.1002/rcm.7039