Cardiovascular (CV) diseases (CVD) are primarily caused by atherosclerotic vascular disease. Atherogenesis is mainly driven by recruitment of leucocytes to the arterial wall, where macrophages contribute to both lipid retention as well as the inflammatory milieu within the vessel wall. Consequently, diseases which present with an enhanced abundance of circulating leucocytes, particularly monocytes, have also been documented to accelerate CVD. A host of metabolic and inflammatory diseases, such as obesity, diabetes, hypercholesteraemia, and rheumatoid arthritis (RA), have been shown to alter myelopoiesis to exacerbate atherosclerosis. Genetic evidence has emerged in humans with the discovery of clonal haematopoiesis of indeterminate potential (CHIP), resulting in a disordered haematopoietic system linked to accelerated atherogenesis. CHIP, caused by somatic mutations in haematopoietic stem and progenitor cells (HSPCs), consequently provide a proliferative advantage over native HSPCs and, in the case of Tet2 loss of function mutation, gives rise to inflammatory plaque macrophages (i.e. enhanced interleukin (IL)-1β production). Together with the recent findings of the CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study) trial that revealed blocking IL-1β using Canakinumab reduced CV events, these studies collectively have highlighted a pivotal role of IL-1β signalling in a population of people with atherosclerotic CVD. This review will explore how haematopoiesis is altered by risk-factors and inflammatory disorders that promote CVD. Further, we will discuss some of the recent genetic evidence of disordered haematopoiesis in relation to CVD though the association with CHIP and suggest that future studies should explore what initiates HSPC mutations, as well as how current anti-inflammatory agents affect CHIP-driven atherosclerosis.
Skip Nav Destination
Article navigation
September 2018
-
Cover Image
Cover Image
A scanning electron micrograph (digitally altered and colourized, 4000× magnification) depicting a mesenchymal stem cell (orange) encapsulated in a self-assembling peptide hydrogel. In volume 132, issue 17 of Clinical Science, McFetridge et al. discuss the use of hydrogel materials to unlock the potential of stem cell therapy to treat chronic kidney disease. This image was provided by the authors and produced in collaboration with Dr Simon Crawford at the Ramaciotti Centre for Cryo-Electron Microscopy, and the Monash Teaching Resource Support Unit.
Review Article|
September 05 2018
Disordered haematopoiesis and cardiovascular disease: a focus on myelopoiesis
Dragana Dragoljevic;
1Haematopoiesis and Leukocyte Biology, Division of Immunometabolism, Baker Heart and Diabetes Research Institute, Melbourne, Australia
2Department of Immunology, Monash University, Melbourne, Australia
Correspondence: Dragana Dragoljevic ([email protected])
Search for other works by this author on:
Marit Westerterp;
Marit Westerterp
3Department of Pediatrics, Section Molecular Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Search for other works by this author on:
Camilla Bertuzzo Veiga;
Camilla Bertuzzo Veiga
1Haematopoiesis and Leukocyte Biology, Division of Immunometabolism, Baker Heart and Diabetes Research Institute, Melbourne, Australia
Search for other works by this author on:
Prabhakara Nagareddy;
Prabhakara Nagareddy
4Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, U.S.A.
Search for other works by this author on:
Andrew J. Murphy
Andrew J. Murphy
1Haematopoiesis and Leukocyte Biology, Division of Immunometabolism, Baker Heart and Diabetes Research Institute, Melbourne, Australia
2Department of Immunology, Monash University, Melbourne, Australia
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
May 02 2018
Revision Received:
July 19 2018
Accepted:
August 01 2018
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Clin Sci (Lond) (2018) 132 (17): 1889–1899.
Article history
Received:
May 02 2018
Revision Received:
July 19 2018
Accepted:
August 01 2018
Citation
Dragana Dragoljevic, Marit Westerterp, Camilla Bertuzzo Veiga, Prabhakara Nagareddy, Andrew J. Murphy; Disordered haematopoiesis and cardiovascular disease: a focus on myelopoiesis. Clin Sci (Lond) 14 September 2018; 132 (17): 1889–1899. doi: https://doi.org/10.1042/CS20180111
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Open Access for all
We offer compliant routes for all authors from 2025. With library support, there will be no author nor reader charges in 5 journals. Check here |
![]() |