Metabolomics analysis reveals an effect of homocysteine on arachidonic acid and linoleic acid metabolism pathway

An increase in serum homocysteine level has been associated with an increased risk of vascular disease; however, the biochemical mechanisms that underlie these effects remain largely unknown. The present study aimed to use high-performance liquid chromatography-mass spectrometry (HPLC-MS) to demonstrate the effects of serum homocysteine on human blood metabolites. A total of 75 fasting serum samples were investigated in the present study. Using a threshold of 15 µmol/l serum homocysteine level, samples were divided into high- and low-homocysteine groups, and the serum extracts were analyzed with an HPLC-MS-based method. A total of 269 features exhibited significant differences and correlation with serum homocysteine levels in the electrospray ionization-positive [ESI(+)] mode, and 69 features were identified in the ESI(−) mode between the two groups. The principal component analysis plot revealed a separation between the high- and the low-homocysteine groups. Metabolite set enrichment analysis identified arachidonic acid metabolism and linoleic acid metabolism as the two pathways with significantly enriched differences. These results revealed that arachidonic acid and linoleic acid metabolism may be associated with serum homocysteine levels and may be involved in homocysteine-induced vascular disease.