Cardiac fibroblasts express the cAMP-adenosine pathway

Area of Science:

• Cardiovascular Biology
• Cell Signaling
• Biochemistry

Background:

• The extracellular cAMP-adenosine pathway involves local adenosine production from extracellular cyclic adenosine monophosphate (cAMP).
• Cardiac fibroblasts play a role in cardiac remodeling, a process implicated in heart disease.

Purpose of the Study:

• To investigate whether the extracellular cAMP-adenosine pathway influences cardiac fibroblast proliferation.
• To explore the potential of targeting this pathway for therapeutic interventions in heart disease.

Main Methods:

• Ventricular cardiac fibroblasts were cultured in 3D matrices.
• Extracellular levels of cAMP metabolites were measured after exogenous cAMP administration.
• Cell growth was assessed via DNA and protein synthesis assays and cell counts.
• Adenosine receptor antagonists and enzyme inhibitors were used to probe pathway mechanisms.

Main Results:

• Exogenous cAMP increased extracellular AMP, adenosine, and inosine in a dose- and time-dependent manner.
• cAMP-induced increases in metabolites were attenuated by phosphodiesterase and ecto-5'-nucleotidase inhibitors.
• Exogenous cAMP significantly inhibited cardiac fibroblast DNA, protein synthesis, and proliferation.
• Inhibition of fibroblast growth by cAMP was mediated through A(2) adenosine receptors and enhanced by inhibiting adenosine metabolism.

Conclusions:

• The extracellular cAMP-adenosine pathway is functional in cardiac fibroblasts and exerts an inhibitory effect on cell growth.
• Pharmacological enhancement of this pathway presents a potential therapeutic strategy to mitigate pathological cardiac remodeling in heart disease.