A(3) adenosine receptor activation during reperfusion reduces infarct size through actions on bone marrow-derived cells. J Mol Cell Cardiol 2010 Aug;49(2):280-6
Date
02/06/2010Pubmed ID
20132822Pubmed Central ID
PMC2885516DOI
10.1016/j.yjmcc.2010.01.018Scopus ID
2-s2.0-77953713842 (requires institutional sign-in at Scopus site) 43 CitationsAbstract
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 30min of coronary occlusion and 24h of reperfusion. Treating B6 wild-type with Cl-IB-MECA during the reperfusion phase (100microg/kg i.v. bolus+0.3microg/kg/min subcutaneously via implantation of Alzet mini-osmotic pumps) reduced myocardial infarct size approximately 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 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.
Author List
Ge ZD, van der Hoeven D, Maas JE, Wan TC, Auchampach JAAuthors
John A. Auchampach PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinTina C. Wan PhD Research Scientist II in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AdenosineAdenosine A3 Receptor Agonists
Animals
Blood Pressure
Bone Marrow Cells
Bone Marrow Transplantation
Cell Movement
Histamine
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Myocardial Infarction
Myocardial Reperfusion Injury
Neutrophils
Receptor, Adenosine A3