Clonal haematopoiesis is driven by acquired somatic mutations in haematopoietic stem and progenitor cells. It leads to a substantial proportion of mutant immune cells, which can influence the inflammatory responses that underlie cardiovascular disease (CVD). Research presented at the ESC Congress 2024 and published simultaneously in the European Heart Journal and Nature Medicine suggests that clonal haematopoiesis is unidirectionally associated with atherosclerosis and that colchicine holds potential therapeutic value.

“Among other mutations, inactivating mutations of TET2, which encodes an epigenetic modifier, drive clonal haematopoiesis,” explains José Javier Fuster. “Previous studies using atherosclerosis-prone Ldlr–/– mice have shown that bone marrow reconstitution with TET2-mutant cells is sufficient for their clonal expansion and increased atherosclerotic plaque size. Further mechanistic studies showed that this accelerated atherosclerosis may be due to the exacerbated production of IL-1β by TET2-deficient macrophages. These findings led us to believe that TET2 mutations contribute causally to the development of atherosclerosis.”