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| Status |
Public on Feb 27, 2024 |
| Title |
Effect of cAMP signaling activation during heart development in Pde2A deficient embryos. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Background: Phosphodiesterases (PDEs) are the enzymes that hydrolyze cyclic nucleotides (cAMP and cGMP) playing a key role in the homeostasis of these two secondary messengers. PDE2A is a dual-specific PDE that breaks down both cAMP and cGMP and can be activated by cGMP. It appears peculiar that the Pde2A-deficient (Pde2A-/-) mouse model is embryonically lethal, likely due to a strongly reduced size of liver and to a severe anemia. In addition, the heart of Pde2A-/- embryos shows ventricular and atrial septum defects, hypertrabeculation, heart dilatation and non-compaction defect. We recently highlighted a direct relationship between Pde2A impairment, consequent increase of cAMP and the onset of mouse congenital heart defects (CHDs), however the molecular mechanisms underlining the heart defects remain unknown. We found a significant modulation of more than 500 genes affecting biological processes involved in the immune system, cardiomyocyte development and contractility, angiogenesis, control of gene transcription and oxidative stress in hearts from Pde2A-/- embryos. Metoprolol and H89 administration were able to prevent 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. By using the antioxidant NAC partial rescue of cardiac defects was observed straightening the oxidative stress like one of the critical molecular mechanisms underpinning the CHDs associated to cAMP unbalance.
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| Overall design |
Transcriptome analysis of Pde2A-/- embryonic heart was performed by RNA sequencing in 5 knockout and 6 wilde-type, the most altered genes were also analyzed by quantitative real time PCR
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| Contributor(s) |
Cardarelli S, Biglietto M, Fustaino V, Benes V, Monaco L, Pellegrini M |
| Citation(s) |
38395995 |
| Submission date |
Jun 07, 2023 |
| Last update date |
Feb 28, 2024 |
| Contact name |
Manuela Pellegrini |
| E-mail(s) |
manuela.pellegrini@cnr.it
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| Organization name |
IBBC-CNR
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| Street address |
Via E Ramarini
|
| City |
Monterotondo |
| State/province |
Rome |
| ZIP/Postal code |
00015 |
| Country |
Italy |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (11)
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| Relations |
| BioProject |
PRJNA981166 |
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