MAT2A promotes atherosclerotic plaque vulnerability by mediating epigenetic reprogramming of macrophages (PRJCA044688)
In order to undertake a systematic investigation into the metabolism of monocytes in atherosclerosis, an untargeted metabolomic profiling of peripheral blood monocytes was performed from patients who were positive for thin-cap fibroatheroma (TCFA) (n=38) in comparison to patients who were negative for TCFA (n=38). The investigation was conducted using a method of mass spectrometry, with the objective of examining the methionine metabolism of monocytes from patients who were TCFA-positive, in comparison to patients who were TCFA-negative. This investigation was performed in both the discovery cohort (n=76) and the validation cohort (n=200).To assess alterations in MAT2A-mediated methionine metabolism within atherosclerosis, mass spectrometry was applied utilizing MAT2A conditional knockout mice, MAT2A specific inhibitor and low-methionine diet.To elucidate the underlying mechanism alleviating atherosclerosis mediated by MAT2A deficiency, the aortas (n = 6 separated pools of 3 mice each per group) were collected from MAT2ACKOApoE-/- and MAT2Afl/flApoE-/- mice fed the HFD for 16 weeks and digested for cell sorting in flow cytometry of plaque macrophages and then analysed using RNA-seq.In order to further elucidate the underlying mechanism mediated by MAT2A deficiency, RNA-seq was utilised to assess the gene expression profiles in bone marrow-derived macrophages (BMDMs) from MAT2ACKO mice (n=3) and control MAT2Afl/fl mice (n=3).