Clonal hematopoiesis and vascular disease

Abstract

Somatic mutations in hematopoietic stem cells are common with aging and can result in expansion of clones harboring mutations, termed clonal hematopoiesis. This results in an increased risk of blood cancers but has also been linked with chronic inflammatory disease states. In recent years, clonal hematopoiesis has been established to have a causative role in atherogenesis and cardiovascular disease. Additionally, as the effector cells have been identified to be immune cells, there is ongoing interest in assessing whether dysregulated immune function plays a role in other chronic inflammatory conditions such as rheumatologic disease. Here, we summarize current understanding of clonal hematopoiesis with a focus on cardiovascular disease and inflammation while outlining the potential, yet unexplored, relationship between clonal hematopoiesis and autoimmune disease. Hematopoietic stem cells (HSCs) continually regenerate blood cells. Acquisition of a somatic mutation that provides a selective advantage, a driver mutation, can result in clonal expansion. Clonal hematopoiesis of indeterminate potential, where somatic mutations in certain cancer-associated genes result in clonal expansion in the absence of overt malignancy, can result in atherosclerotic cardiovascular disease in multiple vascular beds, inflammation, and may also contribute to the pathogenesis of autoimmune disease. Many questions remain unanswered regarding the relationship between clonal hematopoiesis and inflammatory disorders.

Keywords: ASCVD; Atherosclerosis; CHIP; Clonal hematopoiesis; Vascular disease.