Adenosine 2B Receptor Activation Reduces Myocardial Reperfusion Injury by Promoting Anti-Inflammatory Macrophages Differentiation via PI3K/Akt Pathway.
Adenosine 2B Receptor Activation Reduces Myocardial Reperfusion Injury by Promoting Anti-Inflammatory Macrophages Differentiation via PI3K/Akt Pathway.
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腺苷 2B 受体激活通过 PI3K/Akt 途径促进抗炎巨噬细胞分化，减少心肌再灌注损伤
DOI：
10.1155/2015/585297
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发表时间：
2015
影响因子：
--
通讯作者：
Yang Z
中科院分区：
文献类型：
--
作者：
Tian Y;Piras BA;Kron IL;French BA;Yang Z
背景。激活腺苷A2B受体（A2BR）可减轻心肌缺血/再灌注（IR）损伤。然而，a2br介导的心脏保护机制尚不清楚。本研究旨在探讨A2BR介导心脏保护的潜在机制。方法与结果。C57BL/6小鼠缺血40分钟，再灌注60分钟。ATL-801是一种有效的选择性A2BR拮抗剂，不能阻断缺血预处理诱导的保护作用。BAY 60-6583是一种高选择性的A2BR激动剂，可显著降低心肌梗死面积，其保护作用可被ATL-801或wortmannin阻断。BAY 60-6583在再灌注10分钟时增加了心脏磷酸化Akt （p-Akt）水平，这种磷酸化也可以被ATL-801或wortmannin阻断。此外，BAY 60-6583显著增加了再灌注心脏中M2巨噬细胞的浸润，降低了M1巨噬细胞和中性粒细胞的浸润，这一作用也可被wortmannin阻断。同时，共聚焦成像研究显示，在对照组和BAY 60-6583预处理的心脏中，大部分Akt磷酸化都集中在CD206+细胞上。结论。我们的研究结果表明，BAY 60-6583预处理通过其抗炎作用保护心脏免受心肌IR损伤，可能是通过PI3K/Akt通路调节巨噬细胞表型转换。
Background. Activation of the adenosine A2B receptor (A2BR) can reduce myocardial ischemia/reperfusion (IR) injury. However, the mechanism underlying the A2BR-mediated cardioprotection is less clear. The present study was designed to investigate the potential mechanisms of cardioprotection mediated by A2BR. Methods and Results. C57BL/6 mice underwent 40-minute ischemia and 60-minute reperfusion. ATL-801, a potent selective A2BR antagonist, could not block ischemic preconditioning induced protection. BAY 60-6583, a highly selective A2BR 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.
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骨髓来源细胞上的 Adora2b 信号传导可抑制心肌缺血再灌注损伤。
影响因子：
8.8
作者：
Koeppen M;Harter PN;Bonney S;Bonney M;Reithel S;Zachskorn C;Mittelbronn M;Eckle T
通讯作者：
Eckle T
DOI：
10.2174/187153008786848303
发表时间：
2008-12-01
影响因子：
1.9
作者：
Ham, J.;Rees, D. A.
通讯作者：
Rees, D. A.
影响因子：
2.6
作者：
Chen H;Yang D;Carroll SH;Eltzschig HK;Ravid K
通讯作者：
Ravid K
DOI：
10.1124/jpet.111.181792
发表时间：
2011-09-01
影响因子：
3.5
作者：
van der Hoeven, Dharini;Wan, Tina C.;Auchampach, John A.
通讯作者：
Auchampach, John A.
DOI：
10.1152/ajpheart.00181.2010
发表时间：
2010-10-01
影响因子：
4.8
作者：
Methner, Carmen;Schmidt, Katharina;Krieg, Thomas
通讯作者：
Krieg, Thomas