Adenosine 2B Receptor Activation Reduces Myocardial Reperfusion Injury by Promoting Anti-Inflammatory Macrophages Differentiation via PI3K/Akt Pathway. (16th June 2015)

• Record Type: Journal Article
• Authors: Tian, Yikui; Piras, Bryan A.; Kron, Irving L.; French, Brent A.; Yang, Zequan
• Other Names: Xia Zhengyuan Academic Editor.
• Is Part Of: Oxidative medicine and cellular longevity. Volume 2015(2015)
• Publication Date: 2015-06-16
• Subjects: Oxidative stress -- Periodicals; Cells -- Aging -- Periodicals; Cells -- Aging; Oxidative stress; Oxidative Stress -- Periodicals; Cell Aging -- Periodicals; Periodicals; 611.0181
• DOI: 10.1155/2015/585297
• Languages: English
• ISSNs: 1942-0900

Abstract

Abstract : Background . Activation of the adenosineA 2 B receptor (A 2 B R) can reduce myocardial ischemia/reperfusion (IR) injury. However, the mechanism underlying theA 2 B R-mediated cardioprotection is less clear. The present study was designed to investigate the potential mechanisms of cardioprotection mediated byA 2 B R. Methods and Results . C57BL/6 mice underwent 40-minute ischemia and 60-minute reperfusion. ATL-801, a potent selectiveA 2 B R antagonist, could not block ischemic preconditioning induced protection. BAY 60-6583, a highly selectiveA 2 B R 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.