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

Mooney, L., Goodyear, C. S. , Chandra, T., Kirschner, 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)

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, Professor Ninian and Kirschner, Dr Kristina and Copland, Professor Mhairi and Petrie, Professor Mark and Goodyear, Professor Carl and Mooney, Dr Leanne
• Authors: Mooney, L., Goodyear, C. S., Chandra, T., Kirschner, K., Copland, M., Petrie, M. C., and Lang, N. N.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Research Centre: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
• 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

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
303944		BHF Centre of Excellence	Rhian Touyz	British Heart Foundation (BHF)	RE/18/6/34217	CAMS - Cardiovascular Science