Journal article
A(3) adenosine receptor activation during reperfusion reduces infarct size through actions on bone marrow-derived cells
Journal of molecular and cellular cardiology, Vol.49(2), pp.280-286
08/01/2010
DOI: 10.1016/j.yjmcc.2010.01.018
PMID: 20132822
Abstract
The goal of this study was to examine whether the A(3) adenosine receptor (A(3)AR) 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 30 min of coronary occlusion and 24 h of reperfusion. Treating B6 wild-type with Cl-IB-MECA during the reperfusion phase (100 mu g/kg i.v. bolus +0.3 mu g/kg/min subcutaneously via implantation of Alzet mini-osmotic pumps) reduced myocardial infarct size similar to 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 86 congenic A(3)AR gene "knock-out" mice or in chimeric mice lacking the expression of A(3)ARs 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 A(3)AR agonist Cl-IB-MECA at the time of reperfusion provides effective protection from ischemia/reperfusion injury in the heart through activation of the A(3)AR expressed in BM-derived cells, potentially by suppressing the robust inflammatory reaction that occurs during reperfusion and neutrophil-mediated tissue injury. (C) 2010 Elsevier Ltd. All rights reserved.
Details
- Title: Subtitle
- A(3) adenosine receptor activation during reperfusion reduces infarct size through actions on bone marrow-derived cells
- Creators
- Zhi-Dong Ge - Med Coll Wisconsin, Dept Pharmacol & Toxicol, Milwaukee, WI 53226 USADharini van der Hoeven - Medical College of WisconsinJason E. Maas - Medical College of WisconsinTina C. Wan - Medical College of WisconsinJohn A. Auchampach - Medical College of Wisconsin
- Resource Type
- Journal article
- Publication Details
- Journal of molecular and cellular cardiology, Vol.49(2), pp.280-286
- DOI
- 10.1016/j.yjmcc.2010.01.018
- PMID
- 20132822
- ISSN
- 0022-2828
- eISSN
- 1095-8584
- Publisher
- Elsevier
- Number of pages
- 7
- Grant note
- R01HL077707 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) R01 HL077707; R01 HL077707-03; R01 HL077707-05; R01 HL077707-04 / NHLBI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
- Language
- English
- Date published
- 08/01/2010
- Academic Unit
- Oral Pathology, Radiology and Medicine; Dentistry Administration
- Record Identifier
- 9985157465202771
Metrics
1 Record Views