Inhibition of Janus activated kinase-3 protects against myocardial ischemia and reperfusion injury in mice.
Inhibition of Janus activated kinase-3 protects against myocardial ischemia and reperfusion injury in mice.
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DOI：
10.1038/emm.2013.43
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发表时间：
2013-05-17
影响因子：
12.8
通讯作者：
Park, Byung-Hyun
中科院分区：
文献类型：
--
作者：
Oh, Young-Bin;Ahn, Min;Lee, Sang-Myeong;Koh, Hyoung-Won;Lee, Sun-Hwa;Kim, Suhn Hee;Park, Byung-Hyun
Recent studies have documented that Janus-activated kinase (JAK)–signal transducer and activator of transcription (STAT) pathway can modulate the apoptotic program in a myocardial ischemia/reperfusion (I/R) model. To date, however, limited studies have examined the role of JAK3 on myocardial I/R injury. Here, we investigated the potential effects of pharmacological JAK3 inhibition with JANEX-1 in a myocardial I/R model. Mice were subjected to 45 min of ischemia followed by varying periods of reperfusion. JANEX-1 was injected 1 h before ischemia by intraperitoneal injection. Treatment with JANEX-1 significantly decreased plasma creatine kinase and lactate dehydrogenase activities, reduced infarct size, reversed I/R-induced functional deterioration of the myocardium and reduced myocardial apoptosis. Histological analysis revealed an increase in neutrophil and macrophage infiltration within the infarcted area, which was markedly reduced by JANEX-1 treatment. In parallel, in in vitro studies where neutrophils and macrophages were treated with JANEX-1 or isolated from JAK3 knockout mice, there was an impairment in the migration potential toward interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), respectively. Of note, however, JANEX-1 did not affect the expression of IL-8 and MCP-1 in the myocardium. The pharmacological inhibition of JAK3 might represent an effective approach to reduce inflammation-mediated apoptotic damage initiated by myocardial I/R injury.
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影响因子：
20.3
作者：
Gurniak, CB;Berg, LJ
通讯作者：
Berg, LJ
影响因子：
3
作者：
Calvillo, Laura;Vanoli, Emilio;Schwartz, Peter J.
通讯作者：
Schwartz, Peter J.
影响因子：
37.8
作者：
Kumar, AG;Ballantyne, CM;Entman, ML
通讯作者：
Entman, ML
影响因子：
7.3
作者：
Kim, Byung-Hak;Kim, Myunghwan;Baeg, Gyeong-Hun
通讯作者：
Baeg, Gyeong-Hun
影响因子：
3.2
作者：
HATTORI, N;KURAHACHI, H;IMURA, H
通讯作者：
IMURA, H