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Clonal hematopoiesis in cardiovascular disease and therapeutic implications

Abstract

Clonal hematopoiesis arises from somatic mutations that provide a fitness advantage to hematopoietic stem cells and the outgrowth of clones of blood cells. Clonal hematopoiesis commonly involves mutations in genes that are involved in epigenetic modifications, signaling and DNA damage repair. Clonal hematopoiesis has emerged as a major independent risk factor in atherosclerotic cardiovascular disease, thrombosis and heart failure. Studies in mouse models of clonal hematopoiesis have shown an increase in atherosclerosis, thrombosis and heart failure, involving increased myeloid cell inflammatory responses and inflammasome activation. Although increased inflammatory responses have emerged as a common underlying principle, some recent studies indicate mutation-specific effects. The discovery of the association of clonal hematopoiesis with cardiovascular disease and the recent demonstration of benefit of anti-inflammatory treatments in human cardiovascular disease converge to suggest that anti-inflammatory treatments should be directed to individuals with clonal hematopoiesis. Such treatments could target specific inflammasomes, common downstream mediators such as IL-1β and IL-6, or mutations linked to clonal hematopoiesis.

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Fig. 1: Somatic mutations and clonal hematopoiesis: at the crossroads of hematological malignancies and cardiovascular disease.
Fig. 2: Mutation-specific mechanisms linking clonal hematopoiesis to atherosclerotic cardiovascular disease.

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Acknowledgements

A.T. and J.J.F. are supported by a grant from the Leducq Foundation (TNE-18CVD04). A.T. is supported by NIH grant 155431. We thank M. A. Zuriaga for assistance with figure design.

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A.T. and J.J.F. researched the data for the article, provided substantial contributions to discussions of its content, wrote the article and undertook review and/or editing of the manuscript before submission.

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Correspondence to Alan R. Tall or Jose J. Fuster.

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A.T. is a consultant for Amgen and CSL and is on the scientific advisory board of Staten Biotech and 1016 Biotech. J.J.F. declares no potential conflicts of interest.

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Tall, A.R., Fuster, J.J. Clonal hematopoiesis in cardiovascular disease and therapeutic implications. Nat Cardiovasc Res 1, 116–124 (2022). https://doi.org/10.1038/s44161-021-00015-3

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