Angiopoietin-like 2 is essential to aortic valve development in mice.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
21 11 2022
21 11 2022
Historique:
received:
28
02
2022
accepted:
09
11
2022
entrez:
22
11
2022
pubmed:
23
11
2022
medline:
25
11
2022
Statut:
epublish
Résumé
Aortic valve (AoV) abnormalities during embryogenesis are a major risk for the development of aortic valve stenosis (AVS) and cardiac events later in life. Here, we identify an unexpected role for Angiopoietin-like 2 (ANGPTL2), a pro-inflammatory protein secreted by senescent cells, in valvulogenesis. At late embryonic stage, mice knocked-down for Angptl2 (Angptl2-KD) exhibit a premature thickening of AoV leaflets associated with a dysregulation of the fine balance between cell apoptosis, senescence and proliferation during AoV remodeling and a decrease in the crucial Notch signalling. These structural and molecular abnormalities lead toward spontaneous AVS with elevated trans-aortic gradient in adult mice of both sexes. Consistently, ANGPTL2 expression is detected in human fetal semilunar valves and associated with pathways involved in cell cycle and senescence. Altogether, these findings suggest that Angptl2 is essential for valvulogenesis, and identify Angptl2-KD mice as an animal model to study spontaneous AVS, a disease with unmet medical need.
Identifiants
pubmed: 36414704
doi: 10.1038/s42003-022-04243-6
pii: 10.1038/s42003-022-04243-6
pmc: PMC9681843
doi:
Substances chimiques
ANGPTL2 protein, human
0
Angptl2 protein, mouse
0
Angiopoietin-Like Protein 2
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1277Subventions
Organisme : CIHR
ID : 166110
Pays : Canada
Organisme : CIHR
ID : 162446
Pays : Canada
Informations de copyright
© 2022. The Author(s).
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