Preliminary study of metabonomic changes during the progression of atherosclerosis in miniature pigs

BackgroundTo explore potential biomarkers for early diagnosis of atherosclerosis (AS) and provide basic data for further research on AS, the characteristics of serum metabolomics during the progression of AS in mini-pigs were observed dynamically.MethodsAn AS model in Bama miniature pigs was established by a high-cholesterol and high-fat diet. Fasting serum samples were collected monthly for metabolomics and serum lipid detection. At the end of the treatment period, pathological analysis of the abdominal aorta and coronary artery was performed to evaluate the lesions of AS, thereby distinguishing the susceptibility of mini-pigs to AS. The metabolomics was detected using a high-resolution untargeted metabolomic approach. Statistical analysis was used to identify metabolites associated with AS susceptibility.ResultsBased on pathological analysis, mini-pigs were divided into two groups: a susceptible group (n = 3) and a non-susceptible group (n = 6). A total of 1318 metabolites were identified, with significant shifting of metabolic profiles over time in both groups. Dynamic monitoring analysis highlighted 57 metabolites that exhibited an obvious trend of differential changes between two groups with the advance of time. The KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis indicated significant disorders in cholesterol metabolism, primary bile acid metabolism, histidine metabolism, as well as taurine and hypotaurine metabolism.ConclusionsDuring the progression of AS in mini-pigs induced by high-cholesterol/high-fat diet, the alterations in serum metabolic profile exhibited a time-dependent pattern, accompanied by notable disturbances in lipid metabolism, cholesterol metabolism, and amino acid metabolism. These metabolites may become potential biomarkers for early diagnosis of AS. An atherosclerosis model in Bama mini-pigs was established by a high-cholesterol/high-fat diet, but the atherosclerotic lesions distinguished through pathological assessment of main arteries varied among individuals, which may be related to susceptibility. During the progression of atherosclerosis, the alterations in serum metabolic profile were time dependent, accompanied by notable disturbances in lipid metabolism, cholesterol metabolism, and amino acid metabolism. Those metabolites screened by monitoring dynamically may become novel biomarkers for early diagnosis of atherosclerosis.image