title: Quantitative Metabolomic Profiling of Plasma, Urine, and Liver Extracts by1H NMR Spectroscopy Characterizes Different Stages of Atherosclerosis in Hamsters.
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 applied1H NMR-based metabolomics to detect the time-related metabolic profiles of plasma, urine, and liver extracts from male hamsters fed a high fat and 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. Downregulation 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, intestinal microbiota functions, inflammation, and oxidative stress coupled with the metabolisms of cholesterol, fatty acids, saccharides, 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 that1H NMR-based metabolomics is a reliable tool for early diagnosis and monitoring of the process of AS.
authors: State Key Laboratory for Bioactive Substances and Functions of Natural Medicines and ‡Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , No.1 Xiannongtan Street, Beijing 100050, P. R. China.
authors: Wei
authors: W
authors: Guo
authors: State Key Laboratory for Bioactive Substances and Functions of Natural Medicines and ‡Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , No.1 Xiannongtan Street, Beijing 100050, P. R. China.
authors: Chunying
authors: C
authors: Jiang
authors: State Key Laboratory for Bioactive Substances and Functions of Natural Medicines and ‡Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , No.1 Xiannongtan Street, Beijing 100050, P. R. China.
authors: Liu
authors: L
authors: Yang
authors: State Key Laboratory for Bioactive Substances and Functions of Natural Medicines and ‡Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , No.1 Xiannongtan Street, Beijing 100050, P. R. China.
authors: Tianqi
authors: T
authors: Li
authors: State Key Laboratory for Bioactive Substances and Functions of Natural Medicines and ‡Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , No.1 Xiannongtan Street, Beijing 100050, P. R. China.
authors: Xia
authors: X
authors: Liu
authors: State Key Laboratory for Bioactive Substances and Functions of Natural Medicines and ‡Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , No.1 Xiannongtan Street, Beijing 100050, P. R. China.
authors: Mengxia
authors: M
authors: Jin
authors: State Key Laboratory for Bioactive Substances and Functions of Natural Medicines and ‡Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , No.1 Xiannongtan Street, Beijing 100050, P. R. China.
authors: Kai
authors: K
authors: Qu
authors: State Key Laboratory for Bioactive Substances and Functions of Natural Medicines and ‡Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , No.1 Xiannongtan Street, Beijing 100050, P. R. China.
authors: Huili
authors: H
authors: Chen
authors: State Key Laboratory for Bioactive Substances and Functions of Natural Medicines and ‡Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , No.1 Xiannongtan Street, Beijing 100050, P. R. China.
authors: Xiangju
authors: X
authors: Jin
authors: State Key Laboratory for Bioactive Substances and Functions of Natural Medicines and ‡Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , No.1 Xiannongtan Street, Beijing 100050, P. R. China.
authors: Hongyue
authors: H
authors: Liu
authors: State Key Laboratory for Bioactive Substances and Functions of Natural Medicines and ‡Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , No.1 Xiannongtan Street, Beijing 100050, P. R. China.
authors: Haibo
authors: H
authors: Zhu
authors: State Key Laboratory for Bioactive Substances and Functions of Natural Medicines and ‡Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College , No.1 Xiannongtan Street, Beijing 100050, P. R. China.
authors: Yinghong
authors: Y
authors: Wang
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism; D002784:Cholesterol / Q000008:administration & dosage / Q000378:metabolism; D006224:Cricetinae; D018450:Disease Progression; D005227:Fatty Acids / Q000008:administration & dosage / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D008099:Liver / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D055432:Metabolomics; D010949:Plasma / Q000378:metabolism*; D014556:Urine
chemical_list: D005227:Fatty Acids; D002784:Cholesterol
keywords: NMR; atherosclerosis; hamsters; high fat and high cholesterol diet; quantitative metabolomics