Murine models of clonal haematopoiesis to assess mechanisms of cardiovascular disease.
ARCH
CHIP
Cardiovascular disease
Insulin resistance
Somatic mosaicism
Journal
Cardiovascular research
ISSN: 1755-3245
Titre abrégé: Cardiovasc Res
Pays: England
ID NLM: 0077427
Informations de publication
Date de publication:
06 05 2022
06 05 2022
Historique:
received:
25
02
2021
accepted:
21
06
2021
pubmed:
25
6
2021
medline:
11
5
2022
entrez:
24
6
2021
Statut:
ppublish
Résumé
Clonal haematopoiesis (CH) is a phenomenon whereby somatic mutations confer a fitness advantage to haematopoietic stem and progenitor cells (HSPCs) and thus facilitate their aberrant clonal expansion. These mutations are carried into progeny leucocytes leading to a situation whereby a substantial fraction of an individual's blood cells originate from the HSPC mutant clone. Although this condition rarely progresses to a haematological malignancy, circulating blood cells bearing the mutation have the potential to affect other organ systems as they infiltrate into tissues under both homeostatic and disease conditions. Epidemiological and clinical studies have revealed that CH is highly prevalent in the elderly and is associated with an increased risk of cardiovascular disease and mortality. Recent experimental studies in murine models have assessed the most commonly mutated 'driver' genes associated with CH, and have provided evidence for mechanistic connections between CH and cardiovascular disease. A deeper understanding of the mechanisms by which specific CH mutations promote disease pathogenesis is of importance, as it could pave the way for individualized therapeutic strategies targeting the pathogenic CH gene mutations in the future. Here, we review the epidemiology of CH and the mechanistic work from studies using murine disease models, with a particular focus on the strengths and limitations of these experimental systems. We intend for this review to help investigators select the most appropriate models to study CH in the setting of cardiovascular disease.
Identifiants
pubmed: 34164655
pii: 6308561
doi: 10.1093/cvr/cvab215
pmc: PMC9075001
doi:
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1413-1432Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL138014
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL152174
Pays : United States
Organisme : NIA NIH HHS
ID : R21 AG072095
Pays : United States
Informations de copyright
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.
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