Angiopoietin-like 2 is essential to aortic valve development in mice.

Autor: Labbé P; Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada. pauline.labbe@icm-mhi.org.; Faculty of Medicine, Department of Pharmacology, Université de Montréal, Montreal, QC, Canada. pauline.labbe@icm-mhi.org., Munoz Goyette V; Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada.; Faculty of Medicine, Department of Pharmacology, Université de Montréal, Montreal, QC, Canada., Thorin-Trescases N; Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada., Villeneuve L; Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada., Desanlis I; Faculty of Medicine, Department of Medicine, Université de Montréal, Montreal Clinical Research Institute, Montreal, QC, Canada., Delwarde C; Université de Nantes, CNRS, INSERM, l'institut du thorax, Nantes, France., Shi YF; Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada., Martel C; Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada.; Mitologics, Romainville, France., Yu C; Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada.; ThermoFisher, Boston, MA, USA., Alikashani A; Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada., Mamarbachi M; Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada., Lesage F; Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada.; École Polytechnique de Montréal, Université de Montréal, Montreal, QC, Canada., Mathieu S; Faculty of Medicine, Department of Surgery, Université Laval, Quebec, QC, Canada., Tardif JC; Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada.; Faculty of Medicine, Department of Medicine, Université de Montréal, Montreal, QC, Canada., Mathieu P; Faculty of Medicine, Department of Surgery, Université Laval, Quebec, QC, Canada., Kmita M; Faculty of Medicine, Department of Medicine, Université de Montréal, Montreal Clinical Research Institute, Montreal, QC, Canada., Thorin É; Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada.; Faculty of Medicine, Department of Pharmacology, Université de Montréal, Montreal, QC, Canada.; Faculty of Medicine, Department of Surgery, Université de Montréal, Montreal, QC, Canada.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2022 Nov 21; Vol. 5 (1), pp. 1277. Date of Electronic Publication: 2022 Nov 21.
DOI: 10.1038/s42003-022-04243-6
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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