Clonal haematopoiesis of indeterminate potential: intersections between inflammation, vascular disease and heart failure

Mooney, L., Goodyear, C. S. , Chandra, T., Kirshner, K., Copland, M. , Petrie, M. C. and Lang, N. N. (2021) Clonal haematopoiesis of indeterminate potential: intersections between inflammation, vascular disease and heart failure. Clinical Science, 135(7), pp. 991-1007. (doi: 10.1042/CS20200306) (PMID:33861346) (PMCID:PMC8055963)

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Abstract

Ageing is a major risk factor for the development of cardiovascular disease (CVD) and cancer. Whilst the cumulative effect of exposure to conventional cardiovascular risk factors is important, recent evidence highlights clonal haematopoiesis of indeterminant potential (CHIP) as a further key risk factor. CHIP reflects the accumulation of somatic, potentially pro-leukaemic gene mutations within haematopoietic stem cells over time. The most common mutations associated with CHIP and CVD occur in genes that also play central roles in the regulation of inflammation. While CHIP carriers have a low risk of haematological malignant transformation (<1% per year), their relative risk of mortality is increased by 40% and this reflects an excess of cardiovascular events. Evidence linking CHIP, inflammation and atherosclerotic disease has recently become better defined. However, there is a paucity of information about the role of CHIP in the development and progression of heart failure, particularly heart failure with preserved ejection fraction (HFpEF). While systemic inflammation plays a role in the pathophysiology of both heart failure with reduced and preserved ejection fraction (EF), it may be of greater relevance in the pathophysiology of HFpEF, which is also strongly associated with ageing. This review describes CHIP and its pathogenetic links with ageing, inflammation and CVD, while providing insight into its putative role in HFpEF.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Lang, Dr Ninian and Copland, Professor Mhairi and Petrie, Professor Mark and Goodyear, Professor Carl and Mooney, Dr Leanne
Authors: Mooney, L., Goodyear, C. S., Chandra, T., Kirshner, K., Copland, M., Petrie, M. C., and Lang, N. N.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Clinical Science
Publisher:Portland Press
ISSN:0143-5221
ISSN (Online):1470-8736
Published Online:16 April 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Clinical Science 135(7):991-1007
Publisher Policy:Reproduced under a Creative Commons licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
303944BHF Centre of ExcellenceRhian TouyzBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science