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Reviews

Somatic Mutations and Clonal Hematopoiesis

Unexpected Potential New Drivers of Age-Related Cardiovascular Disease

José J. Fuster, Kenneth Walsh
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https://doi.org/10.1161/CIRCRESAHA.117.312115
Circulation Research. 2018;122:523-532
Originally published February 1, 2018
José J. Fuster
From the Molecular Cardiology Unit, Whitaker Cardiovascular Institute, Boston University School of Medicine, MA.
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Kenneth Walsh
From the Molecular Cardiology Unit, Whitaker Cardiovascular Institute, Boston University School of Medicine, MA.
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    • Abstract
    • Aging and Cardiovascular Disease, an Incompletely Understood Connection
    • Somatic Mutations in the Hematopoietic System and Atherosclerotic CVD: Evidence From Human Studies
    • Somatic Mutations in the Hematopoietic System and Atherosclerotic CVD: Evidence From Mouse Studies, the Case of TET2
    • Somatic Mutation-Driven Clonal Hematopoiesis and Atherosclerotic CVD Beyond TET2: Other Genes and Mechanisms?
    • Somatic Mutation-Driven Clonal Hematopoiesis: Many Open Questions
    • Conclusions
    • Acknowledgments
    • Sources of Funding
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Abstract

Increasing evidence shows that conventional cardiovascular risk factors are incompletely predictive of cardiovascular disease, particularly in elderly individuals, suggesting that there may still be unidentified causal risk factors. Although the accumulation of somatic DNA mutations is a hallmark of aging, its relevance in cardiovascular disease or other age-related conditions has been, with the exception of cancer, largely unexplored. Here, we review recent clinical and preclinical studies that have identified acquired mutations in hematopoietic stem cells and subsequent clonal hematopoiesis as a new cardiovascular risk factor and a potential major driver of atherosclerosis. Understanding the mechanisms underlying the connection between somatic mutation-driven clonal hematopoiesis and cardiovascular disease will be highly relevant in the context of personalized medicine, as it may provide key information for the design of diagnostic, preventive, or therapeutic strategies tailored to the effects of specific somatic mutations.

  • aging
  • atherosclerosis
  • cardiovascular disease
  • CHIP
  • inflammation
  • risk factors
  • © 2018 American Heart Association, Inc.
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Circulation Research
February 2, 2018, Volume 122, Issue 3
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Jump to

  • Article
    • Abstract
    • Aging and Cardiovascular Disease, an Incompletely Understood Connection
    • Somatic Mutations in the Hematopoietic System and Atherosclerotic CVD: Evidence From Human Studies
    • Somatic Mutations in the Hematopoietic System and Atherosclerotic CVD: Evidence From Mouse Studies, the Case of TET2
    • Somatic Mutation-Driven Clonal Hematopoiesis and Atherosclerotic CVD Beyond TET2: Other Genes and Mechanisms?
    • Somatic Mutation-Driven Clonal Hematopoiesis: Many Open Questions
    • Conclusions
    • Acknowledgments
    • Sources of Funding
    • Disclosures
    • Footnotes
    • References
  • Figures & Tables
  • Info & Metrics

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    Somatic Mutations and Clonal Hematopoiesis
    José J. Fuster and Kenneth Walsh
    Circulation Research. 2018;122:523-532, originally published February 1, 2018
    https://doi.org/10.1161/CIRCRESAHA.117.312115

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    Somatic Mutations and Clonal Hematopoiesis
    José J. Fuster and Kenneth Walsh
    Circulation Research. 2018;122:523-532, originally published February 1, 2018
    https://doi.org/10.1161/CIRCRESAHA.117.312115
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