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Default Quantitative Metabolomic Profiling of Plasma, Urine and Liver Extracts by 1H NMR Spectroscopy Characterizes Different Stages of Atherosclerosis in Hamsters.

Quantitative Metabolomic Profiling of Plasma, Urine and Liver Extracts by 1H NMR Spectroscopy Characterizes Different Stages of Atherosclerosis in Hamsters.

Related Articles Quantitative Metabolomic Profiling of Plasma, Urine and Liver Extracts by 1H NMR Spectroscopy Characterizes Different Stages of Atherosclerosis in Hamsters.

J Proteome Res. 2016 Aug 29;

Authors: Guo W, Jiang C, Yang L, Li T, Liu X, Jin M, Qu K, Chen H, Jin X, Liu H, Zhu H, Wang Y

Abstract
Atherosclerosis (AS) is a progressive disease that contributes to cardiovascular disease and shows a complex etiology, including genetic and environmental factors. To understand systemic metabolic changes and to identify potential biomarkers correlated with the occurrence and perpetuation of diet-induced AS, we applied 1H NMR-based metabolomics to detect the time-related metabolic profiles of plasma, urine and liver extracts from male hamsters fed a high fat/high cholesterol (HFHC) diet. Conventional biochemical assays and histopathological examinations as well as protein expression analyses were performed to provide complementary information. We found that diet treatment caused obvious aortic lesions, lipid accumulation and inflammatory infiltration in hamsters. Down-regulation of proteins related to cholesterol metabolism, including hepatic SREBP2, LDL-R, CYP7A1, SR-BI, HMGCR, LCAT and SOAT1 was detected, which elucidated the perturbation of cholesterol homeostasis during the HFHC diet challenge. Using "targeted analysis", we quantified 40 plasma, 80 urine and 60 liver hydrophilic extract metabolites. Multivariate analyses of the identified metabolites elucidated sophisticated metabolic disturbances in multiple matrices, including energy homeostasis, inflammation, oxidative stress and intestinal microbiota functions coupled with the metabolism of saccharides, fatty acids, choline, amino acids and nucleotides. For the first time, our results demonstrate a time-dependent metabolic progression of multiple biological matrices in hamsters from physiological status to early AS and further to late-stage AS, demonstrating that 1H NMR-based metabolomics is a reliable tool for early diagnosis and monitoring of the progression of AS.


PMID: 27570155 [PubMed - as supplied by publisher]



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