Cardiac Phosphodiesterases Are Differentially Increased in Diabetic Cardiomyopathy

Diabetic cardiomyopathy (DCM) accomodates a spectrum of cardiac abnormalities. This study aims to investigate whether DCM is associated with changes in cyclic adenosine 3′-5′ monophosphate (cAMP) signaling, particularly cyclic nucleotide phosphodiesterases (PDEs). Type 1 diabetes (T1D) was induced i...

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Published in:Life sciences (1973) 2021-10, Vol.283, p.119857-119857, Article 119857
Main Authors: Hanna, Rita, Nour-Eldine, Wared, Saliba, Youakim, Dagher-Hamalian, Carole, Hachem, Pia, Abou-Khalil, Pamela, Mika, Delphine, Varin, Audrey, El Hayek, Magali Samia, Pereira, Laëtitia, Farès, Nassim, Vandecasteele, Grégoire, Abi-Gerges, Aniella
Format: Article
Language:English
Subjects:
3',5'-Cyclic-nucleotide phosphodiesterase
Abnormalities
Adenosine
Ca2+/calmodulin-dependent phosphodiesterase
Cardiomyopathy
Cyclic adenosine 3′-5′ monophosphate
Cyclic AMP
Diabetes
Diabetes mellitus
Diabetes mellitus (insulin dependent)
Diabetic cardiomyopathy
Echocardiography
Fibrosis
Gene expression
Histology
Immunoassays
Isoforms
Life Sciences
Nucleotides
Phosphodiesterase
Receptors
Signaling
Steatosis
Streptozocin
Structure-function relationships
Type 1 diabetes
β-Adrenergic receptors
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Summary:Diabetic cardiomyopathy (DCM) accomodates a spectrum of cardiac abnormalities. This study aims to investigate whether DCM is associated with changes in cyclic adenosine 3′-5′ monophosphate (cAMP) signaling, particularly cyclic nucleotide phosphodiesterases (PDEs). Type 1 diabetes (T1D) was induced in rats by streptozotocin (STZ, 65 mg/kg) injection. Myocardial remodeling, structure and function were evaluated by histology and echocardiography, respectively. We delineated the sequential changes affecting cAMP signaling and characterized the expression pattern of the predominant cardiac PDE isoforms (PDE 1–5) and β-adrenergic (β-AR) receptors at 4, 8 and 12 weeks following diabetes induction, by real-time quantitative PCR and Western blot. cAMP levels were measured by immunoassays. T1D-induced DCM was associated with cardiac remodeling, steatosis and fibrosis. Upregulation of β1-AR receptor transcripts was noted in diabetic hearts at 4 weeks along with an increase in cAMP levels and an upregulation in the ejection fraction and fraction shortening. However, β2-AR receptors expression remained unchanged regardless of the disease stage. Moreover, we noted an early and specific upregulation of cardiac PDE1A, PDE2A, PDE4B, PDE4D and PDE5A expression at week 4, followed by increases in PDE3A levels in diabetic hearts at week 8. However, DCM was not associated with changes in PDE4A gene expression irrespective of the disease stage. We show for the first time differential and time-specific regulations in cardiac PDEs, data that may prove useful in proposing new therapeutic approaches in T1D-induced DCM. [Display omitted] •Increases in β1-AR receptors, cAMP and cardiac function in 4 week-diabetic hearts.•PDE-1A, 2A, 4B, 4D and 5A expression was upregulated in 4 week-diabetic hearts.•PDE3A levels were increased in 8 week-diabetic rat hearts.•β2-AR receptors and PDE 4A expression was similar in control and diabetic hearts.
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2021.119857