Clonal Hematopoiesis, Cardiovascular Diseases and Hematopoietic Stem Cells

Int J Mol Sci. 2020 Oct 24;21(21):7902. doi: 10.3390/ijms21217902.

Abstract

Cardiovascular diseases and cancer, the leading causes of morbidity and mortality in the elderly, share some common mechanisms, in particular inflammation, contributing to their progression and pathogenesis. However, somatic mutagenesis, a driving force in cancer development, has not been generally considered as an important factor in cardiovascular disease pathology. Recent studies demonstrated that during normal aging, somatic mutagenesis occurs in blood cells, often resulting in expansion of mutant clones that dominate hematopoiesis at advanced age. This clonal hematopoiesis is primarily associated with mutations in certain leukemia-related driver genes and, being by itself relatively benign, not only increases the risks of subsequent malignant hematopoietic transformation, but, unexpectedly, has a significant impact on progression of atherosclerosis and cardiovascular diseases. In this review, we discuss the phenomenon of clonal hematopoiesis, the most important genes involved in it, its impact on cardiovascular diseases, and relevant aspects of hematopoietic stem cell biology.

Keywords: DNMT3A; JAK2; TET2; atherosclerosis; cardiovascular diseases; clonal hematopoiesis; hematopoietic stem cells; inflammatory cytokines; somatic mutagenesis.

Publication types

  • Review

MeSH terms

  • Aged
  • Aging / genetics*
  • Aging / immunology
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / immunology*
  • Clonal Evolution
  • Clonal Hematopoiesis*
  • Genetic Markers
  • Hematopoietic Stem Cells / immunology*
  • Humans
  • Mutation

Substances

  • Genetic Markers