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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
1   Haematopoiesis and Leukocyte Biology, Baker Heart and Diabetes Institute, Melbourne, Australia
,
Dragana Dragoljevic
1   Haematopoiesis and Leukocyte Biology, Baker Heart and Diabetes Institute, Melbourne, Australia
,
Pradeep Natarajan
2   Cardiology Division, Department of Medicine, Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
3   Department of Medical and Population Genetics and the Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States
,
Nan Wang
4   Division of Molecular Medicine, Department of Medicine, Columbia University Medical Center, New York, United States
› Author Affiliations Funding A.J.M is supported by project (APP1142938) and investigator (APP1194329) grants from the National Health and Medical Research Council and a CSL Centenary Award. D.D is supported by a grant from the Jack Brockhoff Foundation (JBF 4867–2021) and Diabetes Australia. P.N. is supported by grants from the National Heart, Lung, and Blood Institute (R01HL142711, R01HL148050, R01HL151283, R01HL127564, R01HL148565, R01HL135242, R01HL151152), National Institute of Diabetes and Digestive and Kidney Diseases (R01DK125782), and Massachusetts General Hospital (Paul and Phyllis Fireman Endowed Chair in Vascular Medicine) and by a grant from Fondation Leducq (TNE-18CVD04). N.W. is supported by grants from the National Heart, Lung, and Blood Institute (R01HL118567, R01HL148071).
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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


Publication History

Received: 08 November 2021

Accepted: 23 February 2022

Accepted Manuscript online:
20 April 2022

Article published online:
18 June 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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