Aging induces cardiac mesenchymal stromal cell senescence and promotes endothelial cell fate of the CD90 + subset.
CD90
IL-1ß
heart
macrophages
mesenchymal stromal cells
senescence
Journal
Aging cell
ISSN: 1474-9726
Titre abrégé: Aging Cell
Pays: England
ID NLM: 101130839
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
29
04
2019
revised:
18
06
2019
accepted:
06
07
2019
pubmed:
30
7
2019
medline:
23
9
2020
entrez:
30
7
2019
Statut:
ppublish
Résumé
Aging is a major risk factor in the development of chronic diseases, especially cardiovascular diseases. Age-related organ dysfunction is strongly associated with the accumulation of senescent cells. Cardiac mesenchymal stromal cells (cMSCs), deemed part of the microenvironment, modulate cardiac homeostasis through their vascular differentiation potential and paracrine activity. Transcriptomic analysis of cMSCs identified age-dependent biological pathways regulating immune responses and angiogenesis. Aged cMSCs displayed a senescence program characterized by Cdkn2a expression, decreased proliferation and clonogenicity, and acquisition of a senescence-associated secretory phenotype (SASP). Increased CCR2-dependent monocyte recruitment by aged cMSCs was associated with increased IL-1ß production by inflammatory macrophages in the aging heart. In turn, IL-1ß induced senescence in cMSCs and mimicked age-related phenotypic changes such as decreased CD90 expression. The CD90+ and CD90- cMSC subsets had biased vascular differentiation potentials, and CD90+ cMSCs were more prone to acquire markers of the endothelial lineage with aging. These features were related to the emergence of a new cMSC subset in the aging heart, expressing CD31 and endothelial genes. These results demonstrate that cMSC senescence and SASP production are supported by the installation of an inflammatory amplification loop, which could sustain cMSC senescence and interfere with their vascular differentiation potentials.
Identifiants
pubmed: 31353772
doi: 10.1111/acel.13015
pmc: PMC6718537
doi:
Substances chimiques
Interleukin-1beta
0
Thy-1 Antigens
0
Interferon-beta
77238-31-4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13015Subventions
Organisme : Conseil Régional Midi-Pyrénées
ID : APRTCN MiPy 2013
Pays : International
Organisme : Conseil Régional Midi-Pyrénées
ID : APRTT MiPy 2011
Pays : International
Organisme : Institut National de la Santé et de la Recherche Médicale
Pays : International
Organisme : Fédération Française de Cardiologie
Pays : International
Informations de copyright
© 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
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