A3 adenosine receptor activation during reperfusion reduces infarct size through actions on bone marrow-derived cells

Zhi-Dong Ge, Dharini van der Hoeven, Jason E. Maas, Tina C. Wan, John A. Auchampach*

*Corresponding author for this work

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

The goal of this study was to examine whether the A3 adenosine receptor (A3AR) agonist Cl-IB-MECA protects against myocardial ischemia/reperfusion injury when administered at the time of reperfusion in an in vivo mouse model of infarction induced by 30min of coronary occlusion and 24h of reperfusion. Treating B6 wild-type with Cl-IB-MECA during the reperfusion phase (100μg/kg i.v. bolus+0.3μg/kg/min subcutaneously via implantation of Alzet mini-osmotic pumps) reduced myocardial infarct size ~37% from 50.1±2.5% in vehicle-treated mice to 31.6±2.8% in Cl-IB-MECA-treated mice, and significantly reduced the number of leukocytes that infiltrated into the ischemic-reperfused myocardium. Cl-IB-MECA did not reduce infarct size or limit leukocyte accumulation in studies using B6 congenic A3AR gene "knock-out" mice or in chimeric mice lacking the expression of A3ARs in bone marrow (BM)-derived cells. Subsequent mechanistic studies demonstrated that Cl-IB-MECA inhibited migration of mouse neutrophils isolated from BM towards the chemotactic substance c5a in trans-well migration assays, and inhibited leukocyte migration into the peritoneal cavity in a mouse model of thioglycollate-induced peritonitis. We conclude that treating with the A3AR agonist Cl-IB-MECA at the time of reperfusion provides effective protection from ischemia/reperfusion injury in the heart through activation of the A3AR expressed in BM-derived cells, potentially by suppressing the robust inflammatory reaction that occurs during reperfusion and neutrophil-mediated tissue injury.

Original languageEnglish (US)
Pages (from-to)280-286
Number of pages7
JournalJournal of Molecular and Cellular Cardiology
Volume49
Issue number2
DOIs
StatePublished - Aug 2010

Keywords

  • Adenosine
  • Adenosine receptors
  • Inflammation
  • Ischemia/reperfusion injury
  • Myocardial infarction

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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