Project description:Clonal hematopoiesis of indeterminate potential (CHIP) is caused by somatic mutations in hematopoietic stem cells and is associated with worse prognosis in heart failure patients. Patients harboring CHIP mutations show enhanced inflammation. However, whether these signatures are derived from the relatively low number of cells harboring mutations or are indicators of a systemic pro-inflammatory activation that is associated with CHIP is unclear. In this study, we assessed the cell-intrinsic effects of CHIP mutant-carrying cells in patients with heart failure. Using an improved protocol to detect mutant cells on a single cell level (MutDetect-Seq), we show that DNMT3A mutant monocytes exhibit altered gene expression profiles associated with inflammation and phagolysosome function. Gene expression was also significantly altered in DNMT3A mutant CD4+ T cells and NK cells, but not CD8 T cells. DNMT3A silenced CD4+ T cells and NK cells showed increased effector functions. Moreover, increased paracrine signaling pathways are predicted and validated between mutated and wild monocytes and T cells, which amplify inflammatory circuits. Taken together, these data provide novel insights into how CHIP might promote worse prognosis in heart failure patients.

2023-06-15 | E-MTAB-13016 | biostudies-arrayexpress

Medical Therapy for Heart Failure Caused by Ischemic Heart Disease.

Project description: Not available

| S-EPMC6534154 | biostudies-literature

Tet2-Mediated Clonal Hematopoiesis Accelerates Heart Failure Through a Mechanism Involving the IL-1?/NLRP3 Inflammasome.

Project description: Not available

| S-EPMC5828038 | biostudies-literature

Full spectrum of clonal haematopoiesis-driver mutations in chronic heart failure and their associations with mortality.

Project description: Not available

| S-EPMC8120376 | biostudies-literature

Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly.

Project description: Not available