In:
Rapid Communications in Mass Spectrometry, Wiley, Vol. 28, No. 22 ( 2014-11-30), p. 2471-2479
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0951-4198
,
1097-0231
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
2002158-6
detail.hit.zdb_id:
58731-X
SSG:
11
