NMR-based metabolomics of urine for the atherosclerotic mouse model using apolipoprotein-E deficient mice.
NMR-based metabolomics of mouse urine was used in conjunction with the traditional staining and imaging of aortas for the characterization of disease advancement, that is, plaque formation in untreated and drug-treated apolipoprotein-E (apoE) knockout mice. The metabolomics approach with multivariate analysis was able to differentiate the captopril-treated from the untreated mice in general agreement with the staining results. Principal component analysis showed a pattern shift in both the drug-treated and untreated samples as a function of time that could possibly be explained as the effect of aging. Allantoin, a marker attributed to captopril treatment was elevated in the drug-treated mice. From partial least squares-discriminant analysis, xanthine and ascorbate were elevated in the untreated mice and were possible markers of plaque formation in the apoE knockout mice. Several additional peaks in the spectra characterizing the study endpoint were found but their respective metabolite identities were unknown.
Leo
Gregory C
GC
Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Welsh and McKean Roads, Spring House, PA 19477-0776, USA. Gleo@its.jnj.com
Darrow
Andrew L
AL
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001057:Apolipoproteins E / Q000172:deficiency; D050197:Atherosclerosis / Q000503:physiopathology*; D015415:Biomarkers / Q000652:urine*; D002216:Captopril / Q000494:pharmacology; D004195:Disease Models, Animal; D009682:Magnetic Resonance Spectroscopy; D055432:Metabolomics; D051379:Mice; D018345:Mice, Knockout; D012015:Reference Standards
D000959:Antihypertensive Agents; D001057:Apolipoproteins E; D015415:Biomarkers; D002216:Captopril