Hematopoiesis of Indeterminate Potential and Atherothrombotic Risk

Andrew J. Murphy; Dragana Dragoljevic; Pradeep Natarajan; Nan Wang

doi:10.1055/a-1830-2147

Thrombosis and Haemostasis, Table of Contents

CC BY-NC-ND 4.0 · Thromb Haemost 2022; 122(09): 1435-1442
DOI: 10.1055/a-1830-2147

Invited Mini Series: Novel Clinical Concepts in Thrombosis

Hematopoiesis of Indeterminate Potential and Atherothrombotic Risk

Andrew J. Murphy

¹Haematopoiesis and Leukocyte Biology, Baker Heart and Diabetes Institute, Melbourne, Australia

,

Dragana Dragoljevic

¹Haematopoiesis and Leukocyte Biology, Baker Heart and Diabetes Institute, Melbourne, Australia

,

Pradeep Natarajan

²Cardiology Division, Department of Medicine, Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States

³Department of Medical and Population Genetics and the Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States

,

Nan Wang

⁴Division of Molecular Medicine, Department of Medicine, Columbia University Medical Center, New York, United States

› Author Affiliations

Abstract

Hematopoiesis is the process of blood production, essential for the continued supply of immune cells and red blood cells. However, the proliferative nature of hematopoietic stem cells (HSCs) renders them susceptible to developing somatic mutations. HSCs carrying a mutation can gain a selective advantage over normal HSCs and result in hematological disorders. One such disorder is termed clonal hematopoiesis of indeterminate potential (CHIP), a premalignant state associated with aging, where the mutant HSCs are responsible for producing a small portion of mature immune cells in the circulation and subsequently in tissues. People with CHIP have been shown to have an increased risk of mortality due to cardiovascular disease (CVD). Why this occurs is under rigorous investigation, but the majority of the studies to date have suggested that increased atherosclerosis is due to heightened inflammatory cytokine release from mutant lesional macrophages. However, given CHIP is driven by several mutations, other hematopoietic lineages can be altered to promote CVD. In this review we explore the relationship between mutations in genes causing CHIP and atherothrombotic disorders, along with potential mechanisms of enhanced clonal outgrowth and potential therapies and strategies to slow CHIP progression.

Keywords

clonal hematopoiesis - atherothrombosis - somatic mutations

Full Text

References

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