The metabolomic study on atherosclerosis mice and its application in a traditional Chinese medicine Sishen granule

Abstract

Although an atherosclerosis (AS) model using low-density lipoprotein receptor deletion mice has been widely applied, its pathological pathway in metabolite level is still not clear. To further reveal the metabolite profile and identify the potential biomarkers in AS development, a serum metabolomic approach was developed based on reversed-phase liquid chromatography/quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS). The established metabolomic platform was also used for elucidating the therapeutic mechanism of a traditional Chinese medicine named Sishen granule (SSKL). Twenty-one potential biomarkers in AS mouse serum were identified. Through functional analysis of these biomarkers, inflammation, proliferation, dysfunction of energy metabolism and amino acid metabolism were considered the most relevant pathological changes in AS. DNA damage products were found for the first time in the metabolomic study of AS. The network established by 20 biomarkers revealed that pyruvate metabolism, citrate cycle, fatty acid metabolism and urea metabolism were seriously disturbed. This metabolomic study not only supplied a systematic view of the progression of AS but also provided a theoretical basis for the treatment of AS. This metabolomic study also demonstrated that SSKL had therapeutic effectiveness for AS through partly reversing the inflammation reaction and amino acid metabolism dysfunction. Copyright © 2015 John Wiley & Sons, Ltd.