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Adenosine 2B Receptor Activation Reduces Myocardial Reperfusion Injury by Promoting Anti-Inflammatory Macrophages Differentiation via PI3K/Akt Pathway.

AbstractBACKGROUND:
Activation of the adenosine A2B receptor (A2BR) can reduce myocardial ischemia/reperfusion (IR) injury. However, the mechanism underlying the A2BR-mediated cardioprotection is less clear. The present study was designed to investigate the potential mechanisms of cardioprotection mediated by A2BR.
METHODS AND RESULTS:
C57BL/6 mice underwent 40-minute ischemia and 60-minute reperfusion. ATL-801, a potent selective A2BR antagonist, could not block ischemic preconditioning induced protection. BAY 60-6583, a highly selective A2BR agonist, significantly reduced myocardial infarct size, and its protective effect could be blocked by either ATL-801 or wortmannin. BAY 60-6583 increased phosphorylated Akt (p-Akt) levels in the heart at 10 min of reperfusion, and this phosphorylation could also be blocked by ATL-801 or wortmannin. Furthermore, BAY 60-6583 significantly increased M2 macrophages and decreased M1 macrophage and neutrophils infiltration in reperfused hearts, which also could be blocked by wortmannin. Meanwhile, confocal imaging studies showed that the majority of Akt phosphorylation in the heart was colocalized to CD206+ cells in both control and BAY 60-6583 pretreated hearts.
CONCLUSION:
Our results indicated that pretreatment with BAY 60-6583 protects the heart against myocardial IR injury by its anti-inflammatory effects, probably by modulating macrophages phenotype switching via a PI3K/Akt pathway.
AuthorsYikui Tian, Bryan A Piras, Irving L Kron, Brent A French, Zequan Yang
JournalOxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2015 Pg. 585297 ( 2015) ISSN: 1942-0994 [Electronic] United States
PMID26161239 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Adenosine A2 Receptor Agonists
  • Adenosine A2 Receptor Antagonists
  • Aminopyridines
  • Androstadienes
  • BAY 60-6583
  • Receptor, Adenosine A2B
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Wortmannin
Topics
  • Adenosine A2 Receptor Agonists (pharmacology)
  • Adenosine A2 Receptor Antagonists (pharmacology)
  • Aminopyridines (pharmacology)
  • Androstadienes (pharmacology)
  • Animals
  • Cell Differentiation (drug effects)
  • Heart Rate (drug effects)
  • Ischemic Preconditioning, Myocardial
  • Macrophages (cytology, drug effects, metabolism)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Confocal
  • Myocardial Infarction (prevention & control)
  • Myocardial Reperfusion Injury (metabolism, pathology)
  • Neutrophil Infiltration (drug effects)
  • Phosphatidylinositol 3-Kinases (metabolism)
  • Phosphorylation (drug effects)
  • Proto-Oncogene Proteins c-akt (metabolism)
  • Receptor, Adenosine A2B (chemistry, metabolism)
  • Signal Transduction
  • Wortmannin

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