Open AccessClonal haematopoiesis: connecting ageing and inflammation in cardiovascular disease
Author(s) -
Siddhartha Jaiswal,
Peter Libby
Publication year - 2019
Publication title -
nature reviews. cardiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.495
H-Index - 130
eISSN - 1759-5010
pISSN - 1759-5002
DOI - 10.1038/s41569-019-0247-5
Subject(s) - haematopoiesis , inflammation , disease , medicine , somatic cell , immunology , ageing , immune system , innate immune system , cancer research , bioinformatics , stem cell , gene , biology , genetics
Ageing and inflammation strongly drive the risk of cardiovascular disease. Work over the past decade has uncovered a common condition characterized by the positive selection of certain somatic mutations in haematopoietic stem cells in ageing humans. This phenomenon, known as clonal haematopoiesis of indeterminate potential (CHIP), occurs most commonly as a result of mutations in the transcriptional regulators DNMT3A, TET2 and ASXL1. CHIP is associated with a variety of adverse outcomes, including haematological cancer and death. Surprisingly, CHIP is also associated with a doubling of the risk of atherosclerotic cardiovascular disease. Studies in mice support the causality of this relationship. Mutations in TET2, which are among the most commonly found mutations in CHIP, lead to increased expression of inflammatory genes in innate immune cells, potentially explaining the link between mutations and increased cardiovascular risk. Therapies targeting the mutant clones or the increased inflammatory mediators might be useful for ameliorating the risk of cardiovascular disease. We propose that the mutations leading to clonal haematopoiesis contribute to the increased inflammation seen in ageing and thereby explain some of the age-related risk of cardiovascular disease.