Age associated, acquired mutations in circulating blood cells associates with development of cardiovascular diseases and a worse prognosis for patients who already have heart failure. However, these mutations often occur in just 2-8% of immune cells. How a relatively small number of mutant cells seems to have such an outsize impact has was not understood. A team led by Professor Stefanie Dimmeler, head of the Institute of Cardiovascular Regeneration at Johann Goethe University of Frankfurt, and first authors Professor Wesley Abplanalp and Dr. Bianca Schuhmacher have developed a novel technology allowing for detection of cells harbouring somatic mutations, using high throughput single cell RNA-sequencing. With this technology the authors were able to find that monocytes appear to be disproportionately affected by DNMT3A mutations, compared to other circulating cell types. Importantly, the authors demonstrated that monocytes harbouring DNMT3A mutations have heightened inflammatory signalling profiles. Moreover, they found that these mutant monocytes are also more likely to signal to other immune cells, causing even greater inflammatory and activation profiles. The consequence of such activation for cardiac resident cells suggested that there could be enhanced cardiac fibroblast activation and cardiomyocyte hypertrophy, both important indicators for a worsening prognosis in heart failure patients. While the novel technological development can be applied to other scientific questions, the use in this instance can be leveraged to find drugs that targetedly treat clonal hematopoiesis associated heart failure conditions.
Link to the publication: Cell-intrinsic effects of clonal hematopoiesis in heart failure