title: A2 Adenosine Receptor-mediated Cardioprotection Against Reperfusion Injury in Rat Hearts Is Associated With Autophagy Downregulation.
abstract: This study was undertaken to determine and confer the cardioprotective effects of the adenosine A2 receptor (A2AR) and its impact on myocardial autophagy in the setting of reperfusion. We established a rat ischemia model by subjecting rats to 30 minutes of ischemia (I) and 120 minutes of reperfusion (R). The A2AR agonists CGS21680 (A2aAR specific) and BAY60-6583 (A2bAR specific) were administered separately and in combination 5 minutes before reperfusion (postconditioning). No visible improvements in the rats' hemodynamic changes in response to either CGS or BAY were observed compared with untreated control groups (I/R). BAY significantly reduced infarct sizes, whereas CGS did not. Electron microscopy, enzyme-linked immunosorbent assay and TUNEL apoptosis staining results demonstrated that CGS and BAY play cardioprotective roles by maintaining mitochondria structural stability, decreasing serum cardiac troponin I (cTnI) concentrations and decreasing the number of apoptotic cells. CGS21680 and BAY60-6583 slightly increased the expression (vs. I/R group) of Bcl-2 and significantly attenuated the expression of Beclin-1, LC3B, and LAMP-2, as analyzed by Western blot, compared with the I/R alone group. Notably, BAY60-6583 exerts a predominant effect on mitochondria structural stabilization, apoptotic inhibition, and attenuation of LC3B/LAMP-2 expression. No synergistic effects were observed for the 2 agonists. Our data suggest that A2AR-mediated cardioprotection is associated with Beclin-1-induced autophagy downregulation in the setting of reperfusion. A2bAR activation exerts stronger cardioprotective effects against I/R injury compared with A2aAR.
authors.affiliation: *Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, China; †Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China; and ‡Laboratory of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Jianjuan
authors.initials: J
authors.lastname: Ke
authors.forename: Bo
authors.initials: B
authors.lastname: Yao
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Shanshan
authors.initials: S
authors.lastname: Cui
authors.forename: Huang
authors.initials: H
authors.lastname: Ding
mesh_terms: D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043683:Receptors, Adenosine A2 / Q000502:physiology*
chemical_list: D058908:Adenosine A2 Receptor Agonists; D043683:Receptors, Adenosine A2