# Clonal Hematopoiesis in Cardiovascular Risk: Focus on Inflammatory Mechanisms

## TL;DR

This review explores how clonal hematopoiesis, particularly CHIP, contributes to cardiovascular disease through inflammatory mechanisms.

## Contribution

The paper provides a focused review on inflammatory mechanisms linking CHIP to cardiovascular risk.

## Key findings

- CHIP is associated with an increased risk of cardiovascular disease.
- Mutations in DNMT3A, TET2, ASXL1, and JAK2 are key subtypes linked to inflammation and atherosclerosis.
- Proinflammatory immune cells from CHIP may drive atherosclerosis progression.

## Abstract

Clonal hematopoiesis (CH) is the expansion of clones from a single hematopoietic stem cell (HSC) in the bone marrow. Clonal hematopoiesis of indeterminate potential (CHIP) refers to CH defined by the presence of pre-leukemic driver mutations in at least 2% of alleles in sequenced peripheral blood. This phenomenon is, by definition, associated not only with the future development of acute myeloid leukemia but also with non-malignant conditions, including cardiovascular disease. However, the underlying molecular mechanisms for CH in non-malignant diseases, such as cardiovascular disease, are not fully explained. Certain subtypes of CHIP may give rise to proinflammatory immune cells, which, in turn, may promote atherosclerosis progression. Key subtypes of CHIP include mutations in genes encoding epigenetic regulators DNMT3A (DNA methyltransferase 3A), TET2 (ten-eleven translocation methylcytosine dioxygenase 2), and ASXL1 (associated sex combs-like 1), as well as mutations in the gene encoding hematopoietic cytokine signaling: JAK2 (Janus kinase 2). The aim of this review is to summarize the current knowledge of CHIP and its association with inflammation and cardiovascular risk factors.