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June 30, 2017Frontiers in PharmacologyOpen Access

Stimulation of Adenosine A2B Receptor Inhibits Endothelin-1-Induced Cardiac Fibroblast Proliferation and α-Smooth Muscle Actin Synthesis Through the cAMP/Epac/PI3K/Akt-Signaling Pathway

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Key result

Stimulation of the adenosine A2B receptor significantly inhibited endothelin-1-induced cardiac fibroblast proliferation and α-smooth muscle actin expression via the cAMP/Epac/PI3K/Akt signaling pathway.

Why the study?

Does adenosine A2 receptor agonist CV1808 prevent ET-1-induced cell proliferation and α-SMA expression in neonatal rat cardiac fibroblasts?

Population

Neonatal Sprague-Dawley rat cardiac fibroblasts

Comparison

Adenosine A2 receptor agonist CV1808 for 1 hour… vs Vehicle prior to Endothelin-1 stimulation

Design

Preclinical

Authors

SPSarawuth PhosriMahidol UniversityAAAjaree ArieyawongMahidol UniversityKBKwanchai BunrukchaiMahidol University

Discussion

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Implication

May not yet guide antifibrotic therapy; leaves open A2B receptor as a target for cardiac fibrosis research.

Structured PICO

Does adenosine A2 receptor agonist CV1808 prevent ET-1-induced cell proliferation and α-SMA expression in neonatal rat cardiac fibroblasts?

P
Population
In vitro study using neonatal rat cardiac fibroblasts to evaluate the mechanisms of cardioprotective effects of adenosine receptor agonists.
I
Intervention
Adenosine A2 receptor agonist CV1808 (1-50 µM) for 1 hour prior to Endothelin-1 (20 nM) stimulation for 12-24 hours
C
Comparator
Vehicle (control) prior to Endothelin-1 (20 nM) stimulation
O
Outcome
Cell proliferation (assessed by MTT assay) and α-SMA mRNA and protein expressionsurrogate

Main Result

p-value: p=<0.05

Stimulation of the adenosine A2B receptor inhibits ET-1-induced cardiac fibroblast proliferation and α-SMA synthesis via the cAMP/Epac/PI3K/Akt pathway, identifying a potential therapeutic target for cardiac fibrosis.

Limitations

  • In vitro experiment using cardiac fibroblasts may not completely apply for clinical use due to lacking in vivo and clinical studies
  • MTT assay may not completely apply for investigation of antiproliferative effect
  • Restorative roles of A2B receptor following ET-1 administration have not been determined

Cite This Study

Phosri et al. (2017) studied Cardiac fibrosis. Adenosine A2B receptor agonist (CV1808) vs. Vehicle / ET-1 alone was evaluated on ET-1-induced fibroblast proliferation and α-SMA expression (p=<0.05). Stimulation of the adenosine A2B receptor significantly inhibited endothelin-1-induced cardiac fibroblast proliferation and α-smooth muscle actin expression via the cAMP/Epac/PI3K/Akt signaling pathway.

synapsesocial.com/papers/6a21bd408d200acffec0ad7chttps://doi.org/10.3389/fphar.2017.00428
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Also Consider

Synapse has enriched 4 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Exogenous and Endogenous Adenosine Inhibits Fetal Calf Serum–Induced Growth of Rat Cardiac Fibroblasts1997 · 140 citations
  2. 2Functional effects of enhancing or silencing adenosine A 2b receptors in cardiac fibroblasts2004 · 84 citations
  3. 3Activation of Adenosine A 1 Receptor Attenuates Cardiac Hypertrophy and Prevents Heart Failure in Murine Left Ventricular Pressure-Overload Model2003 · 128 citations
  4. 4Adenosine receptor involvement in a delayed phase of myocardial protection 24 hours after ischemic preconditioning.1994 · 274 citations