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Clonal hematopoiesis driven by somatic mutations: A new player in atherosclerotic cardiovascular disease

      Highlights

      • Somatic mutation-driven clonal hematopoiesis has emerged as an independent risk factor forcardiovascular disease.
      • Experimental studies are testing the hypothesis that clonal hematopoiesis promotes inflammation and atherosclerosis.
      • Mechanistic studies may provide rationale for the development of personalized preventive care strategies or therapies.
      • Further research is required to understand this new cardiovascular risk factor and its clinical management.

      Abstract

      The accumulation of acquired mutations is an inevitable consequence of the aging process, but its pathophysiological relevance has remained largely unexplored beyond cancer. Most of these mutations have little or no functional consequences, but in a few rare instances, a mutation may arise that confers a competitive advantage to a stem cell, leading to its clonal expansion. When such a mutation occurs in hematopoietic stem cells, it leads to a situation of clonal hematopoiesis, which has the potential to affect multiple tissues beyond the bone marrow, as the clonal expansion of the mutant stem cell is extended to circulating blood cells and tissue-infiltrating immune cells. Recent genomics and experimental studies have provided support to the notion that this somatic mutation-driven clonal hematopoiesis contributes to vascular inflammation and the development of atherosclerosis and related cardiovascular and cerebrovascular ischemic events. Here, we review our current understanding of this emerging cardiovascular risk modifier and the mechanisms underlying its connection to atherosclerosis development.

      Keywords

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