The Hypoxia-Adenosine Link during Myocardial Ischemia-Reperfusion Injury.
The Hypoxia-Adenosine Link during Myocardial Ischemia-Reperfusion Injury.
复制标题
心肌缺血再灌注损伤中的缺氧-腺苷连接
DOI：
10.3390/biomedicines10081939
复制
发表时间：
2022-08-10
期刊：
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
作者：
尽管越来越多的可用性和更成功的介入方法恢复冠状动脉再灌注，心肌缺血再灌注损伤是世界范围内发病率和死亡率的重要原因。心肌缺血时，心肌深度缺氧，导致缺氧诱导转录因子（HIF）稳定。HIF的稳定导致转录程序促进对缺氧的适应和细胞存活。HIF稳定的转录后果包括细胞外生产和腺苷信号效应的增加。胞外腺苷作为一种信号分子，通过激活腺苷受体发挥作用。一些研究暗示腺苷信号在心脏保护中，特别是通过激活Adora2a和Adora2b受体。腺苷受体激活可通过免疫细胞的信号事件导致代谢适应以增强缺血耐受性或抑制心肌再灌注损伤。许多研究强调，针对缺氧-腺苷连接的临床策略可以考虑进行临床试验。这可以通过使用药理学HIF激活剂或通过直接增强细胞外腺苷产生或信号传导作为急性心肌梗死患者或接受心脏手术的治疗来实现。
Despite increasing availability and more successful interventional approaches to restore coronary reperfusion, myocardial ischemia-reperfusion injury is a substantial cause of morbidity and mortality worldwide. During myocardial ischemia, the myocardium becomes profoundly hypoxic, thus causing stabilization of hypoxia-inducible transcription factors (HIF). Stabilization of HIF leads to a transcriptional program that promotes adaptation to hypoxia and cellular survival. Transcriptional consequences of HIF stabilization include increases in extracellular production and signaling effects of adenosine. Extracellular adenosine functions as a signaling molecule via the activation of adenosine receptors. Several studies implicated adenosine signaling in cardioprotection, particularly through the activation of the Adora2a and Adora2b receptors. Adenosine receptor activation can lead to metabolic adaptation to enhance ischemia tolerance or dampen myocardial reperfusion injury via signaling events on immune cells. Many studies highlight that clinical strategies to target the hypoxia-adenosine link could be considered for clinical trials. This could be achieved by using pharmacologic HIF activators or by directly enhancing extracellular adenosine production or signaling as a therapy for patients with acute myocardial infarction, or undergoing cardiac surgery.
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影响因子：
13.6
作者：
Antonioli L;Pacher P;Vizi ES;Haskó G
通讯作者：
Haskó G
影响因子：
3
作者：
Bao, Weike;Qin, Pu;Willette, Robert N.
通讯作者：
Willette, Robert N.
DOI：
10.1056/nejmra1802337
发表时间：
2021-02-11
期刊：
The New England journal of medicine
影响因子：
--
作者：
Allada R;Bass J
通讯作者：
Bass J
影响因子：
3.1
作者：
Aherne CM;Collins CB;Eltzschig HK
通讯作者：
Eltzschig HK
影响因子：
3.5
作者：
Colgan, Sean P;Eltzschig, Holger K;Eckle, Tobias;Thompson, Linda F
通讯作者：
Thompson, Linda F