ASXL1 mutation accelerates atherosclerosis by promoting activation of myeloid cells

Abstract

Clonal hematopoiesis of cells carrying an ASXL1 mutation promotes atherosclerosis. An unexpected function of ASXL1 — direct inhibition of IL-1 receptor and Toll-like receptor signaling — was lost by ASXL1 mutation, leading to prolonged inflammation. IRAK inhibitors reduced the atherosclerotic plaque size, implicating IRAK inhibitors in the therapies of cardiovascular diseases driven by ASXL1-associated clonal hematopoiesis.