Metabonomic Changes Associated with Atherosclerosis Progression for LDLR(-/-) Mice

Journal of Proteome Research
Dan LiHuiru Tang

Abstract

Atherosclerosis resulting from hyperlipidemia causes many serious cardiovascular diseases. To understand the systems changes associated with pathogenesis and progression of atherosclerosis, we comprehensively analyzed the dynamic metabonomic changes in multiple biological matrices of LDLR(-/-) mice using NMR and GC-FID/MS with gene expression, clinical chemistry, and histopathological data as well. We found that 12 week "Western-type" diet (WD) treatment caused obvious aortic lesions, macrophage infiltration, and collagen level elevation in LDLR(-/-) mice accompanied by up-regulation of inflammatory factors including aortic ICAM-1, MCP-1, iNOS, MMP2, and hepatic TNFα and IL-1β. The WD-induced atherosclerosis progression was accompanied by metabonomic changes in multiple matrices including biofluids (plasma, urine) and (liver, kidney, myocardial) tissues involving multiple metabolic pathways. These included disruption of cholesterol homeostasis, disturbance of biosynthesis of amino acids and proteins, altered gut microbiota functions together with metabolisms of vitamin-B3, choline, purines, and pyrimidines. WD treatment caused down-regulation of SCD1 and promoted oxidative stress reflected by urinary allantoin elevation and dec...Continue Reading

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Citations

Jul 15, 2015·Current Opinion in Clinical Nutrition and Metabolic Care·E Angela MurphyKyle M Herbert
Dec 3, 2016·Nature Reviews. Cardiology·Annika Lindskog Jonsson, Fredrik Bäckhed
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Jun 9, 2016·Journal of Proteome Research·Junfang WuHuiru Tang
Jul 26, 2017·Journal of Agricultural and Food Chemistry·Yuhui YangGuowei Le

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