Display options
Cite
Castro-Perez J, Hatcher N, Kofi Karikari N, et al. In vivo isotopically labeled atherosclerotic aorta plaques in ApoE KO mice and molecular profiling by matrix-assisted laser desorption/ionization mass spectrometric imaging. Rapid Commun Mass Spectrom. 2014;28(22):2471-9doi: 10.1002/rcm.7039.
Castro-Perez, J., Hatcher, N., Kofi Karikari, N., Wang, S. P., Mendoza, V., Shion, H., Millar, A., Shockcor, J., Towers, M., McLaren, D., Shah, V., Previs, S., Akinsanya, K., Cleary, M., Roddy, T. P., & Johns, D. G. (2014). In vivo isotopically labeled atherosclerotic aorta plaques in ApoE KO mice and molecular profiling by matrix-assisted laser desorption/ionization mass spectrometric imaging. Rapid communications in mass spectrometry : RCM, 28(22), 2471-9. https://doi.org/10.1002/rcm.7039
Castro-Perez, Jose, et al. "In vivo isotopically labeled atherosclerotic aorta plaques in ApoE KO mice and molecular profiling by matrix-assisted laser desorption/ionization mass spectrometric imaging." Rapid communications in mass spectrometry : RCM vol. 28,22 (2014): 2471-9. doi: https://doi.org/10.1002/rcm.7039
Castro-Perez J, Hatcher N, Kofi Karikari N, Wang SP, Mendoza V, Shion H, Millar A, Shockcor J, Towers M, McLaren D, Shah V, Previs S, Akinsanya K, Cleary M, Roddy TP, Johns DG. In vivo isotopically labeled atherosclerotic aorta plaques in ApoE KO mice and molecular profiling by matrix-assisted laser desorption/ionization mass spectrometric imaging. Rapid Commun Mass Spectrom. 2014 Nov 30;28(22):2471-9. doi: 10.1002/rcm.7039. PMID: 25303476.
Copy Download .nbib Format: NLM
Share it on

Rapid Commun Mass Spectrom. 2014 Nov 30;28(22):2471-9. doi: 10.1002/rcm.7039.

In vivo isotopically labeled atherosclerotic aorta plaques in ApoE KO mice and molecular profiling by matrix-assisted laser desorption/ionization mass spectrometric imaging.

Rapid communications in mass spectrometry : RCM

Jose Castro-Perez, Nathan Hatcher, Nana Kofi Karikari, Sheng-Ping Wang, Vivienne Mendoza, Henry Shion, Alan Millar, John Shockcor, Mark Towers, David McLaren, Vinit Shah, Stephen Previs, Karen Akinsanya, Michele Cleary, Thomas P Roddy, Douglas G Johns

Affiliations

  1. Merck & Co., Inc, Merck Research Laboratories, Kenilworth, NJ, 07033, USA.

PMID: 25303476 DOI: 10.1002/rcm.7039

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-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.

Publication Types