Integrated application of transcriptome and metabolomics reveals potential therapeutic targets for the polarization of atherosclerotic macrophages

Abstract

The polarization of macrophages often leads to severe calcification and necrosis in aged atherosclerotic plaques, which eventually leads to poor prognosis of ischaemic cardiovascular and cerebrovascular diseases. More reliable diagnostic methods are urgently needed to discover therapeutic targets of macrophage polarization in aged atherosclerotic plaques. Metabolomics of aged plaques (n = 20) and macrophage polarization transcriptomes (n = 30) were integrated to identify metabolic therapeutic targets of macrophage polarization associated with aged plaque. Finally, metabolic inhibitors were used to verify the reliability of the target genes. Integrated multiomics analysis revealed that 6 metabolic pathways (including 21 genes) regulate macrophage polarization in aged atherosclerosis. Targeted treatment of macrophage polarization with metabolic inhibitors can effectively reduce the adverse risk of aged atherosclerosis. The combination of transcriptomics and metabolomics approaches can identify effective therapeutic targets for macrophage polarization in arteriosclerosis.

Keywords: Atherosclerotic plaque; Macrophage polarization; Metabonomics; Multimomics analysis; Transcriptomics.