Non-preferential, but detrimental accumulation of macrophages with clonal hematopoiesis-driver mutations in cardiovascular tissues
Dederichs, T.-s.; Yerdenova, A.; Horstmann, H.; Vico, T.; Nuebling, S.; Peyronnet, R.; von zur Muehlen, C.; Heidt, T.; Wolf, D.; Westermann, D.; Hilgendorf, I.
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Clonal hematopoiesis of indeterminate potential (CHIP) is an acquired genetic risk factor for cardiovascular (CV) disease, supposedly mediated by pro-inflammatory recruited monocytes1-15. However, how these cells and their progeny behave in the CV tissue remains unclear. Here, we studied human carotid artery plaque and heart tissue samples from DNMT3A or TET2 mutation carriers to quantify the relative accumulation of mutated macrophages and to characterize tissue macrophages from carriers compared to non-carriers. Using droplet digital polymerase chain reaction (ddPCR), we detected similar sizes of CHIP clones in circulating monocytes and macrophages from atheromas and heart tissues, even among CCR2+ (infiltrative), and CCR2- (resident) cardiac macrophages. Using bulk RNA-sequencing (RNA-seq), we revealed a pro-inflammatory gene profile of myeloid cells from CHIP carriers compared to non-carriers. In summary, quantitatively, CHIP mutated myeloid cells did not preferentially accumulate in CV tissues, but qualitatively, they expressed a more disease-prone phenotype.
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