| Autor: |
Silvia Cardarelli, Martina Biglietto, Tiziana Orsini, Valentina Fustaino, Lucia Monaco, Ana Gabriela de Oliveira do Rêgo, Francesca Liccardo, Silvia Masciarelli, Francesco Fazi, Fabio Naro, Luciana De Angelis, Manuela Pellegrini |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Cell Death and Disease, Vol 15, Iss 2, Pp 1-13 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2041-4889 |
| DOI: |
10.1038/s41419-024-06549-1 |
| Popis: |
Abstract Phosphodiesterase 2A (Pde2A) is a dual-specific PDE that breaks down both cAMP and cGMP cyclic nucleotides. We recently highlighted a direct relationship between Pde2A impairment, a consequent increase of cAMP, and the appearance of mouse congenital heart defects (CHDs). Here we aimed to characterize the pathways involved in the development of CHDs and in their prevention by pharmacological approaches targeting cAMP and cGMP signaling. Transcriptome analysis revealed a modulation of more than 500 genes affecting biological processes involved in the immune system, cardiomyocyte development and contractility, angiogenesis, transcription, and oxidative stress in hearts from Pde2A −/− embryos. Metoprolol and H89 pharmacological administration prevented heart dilatation and hypertabeculation in Pde2A −/− embryos. Metoprolol was also able to partially impede heart septum defect and oxidative stress at tissue and molecular levels. Amelioration of cardiac defects was also observed by using the antioxidant NAC, indicating oxidative stress as one of the molecular mechanisms underpinning the CHDs. In addition, Sildenafil treatment recovered cardiac defects suggesting the requirement of cAMP/cGMP nucleotides balance for the correct heart development. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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