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[Preprint]. 2023 Jul 26:2023.07.22.23292754. [Version 1] doi: 10.1101/2023.07.22.23292754

Figure 1.

Figure 1

Central illustration – important novel findings from this study. Left panel: Over 300 CHIP mutation carriers from the Munich cardIovaScular StudIes biObaNk (MISSION) and the Stockholm-Tartu Atherosclerosis Reverse Networks Engineering Task (STARNET) studies were evaluated. Upper panel: In our study, we confirmed blood derived CHIP mutations in human atherosclerotic plaques of coronary artery, carotids and heart muscle on DNA level. Middle panel: For the first time we were able to visualize macrophages with specific DNMT3A CHIP mutations using mutaFISH™ at single cell resolution in human atherosclerotic plaques. Enrichment of CHIP mutated cells in human plaques was confirmed. Lower panel: Previously unknown pro-atherosclerotic alterations in gene expression of CHIP mutated macrophages at the level of regulatory key-drivers, pathways, networks, and modules with relevance for CAD progression were identified. ASXL1: ASXL Transcriptional Regulator 1; CAD: Coronar artery disease; CHIP: Clonal hematopoiesis of indeterminate potential; DNMT3A: DNA Methyltransferase 3 Alpha; HSC: hematopoietic stem cell; mutaFISH: mutation-specific Fluorescence In Situ Hybridization; TET2: Tet Methylcytosine Dioxygenase 2.