Sarah Karam, Jean Piero Margaria, Aurélia Bourcier, Delphine Mika, Audrey Varin, Ibrahim Bedioune, Marta Lindner, Kaouter Bouadjel, Matthieu Dessillons, Françoise Gaudin, Florence Lefebvre, Philippe Mateo, Patrick Lechêne, Susana Gomez, Valérie Domergue, Pauline Robert, Charlène Coquard, Vincent Algalarrondo, Jane-Lise Samuel, Jean-Baptiste Michel, Flavien Charpentier, Alessandra Ghigo, Emilio Hirsch, Rodolphe Fischmeister, Jérôme Leroy, Grégoire Vandecasteele
Background: The cAMP-hydrolyzing phosphodiesterase 4B (PDE4B) is a key negative regulator of cardiac β-adrenergic receptor (β-AR) stimulation. PDE4B deficiency leads to abnormal Ca2+ handling and PDE4B is decreased in pressure overload hypertrophy, suggesting that increasing PDE4B in the heart is beneficial in heart failure (HF). Methods: We measured PDE4B expression in human cardiac tissues, developed two transgenic mouse lines with cardiomyocyte-specific overexpression of PDE4B (PDE4B-TG), and an adeno-associated virus serotype 9 encoding PDE4B (AAV9-PDE4B)...
April 8, 2020: Circulation