Heat-shock transcription factor 1 is critically involved in the ischaemia-induced cardiac hypertrophy via JAK2/STAT3 pathway.
Heat-shock transcription factor 1 is critically involved in the ischaemia-induced cardiac hypertrophy via JAK2/STAT3 pathway.
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DOI：
10.1111/jcmm.13713
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发表时间：
2018-09
影响因子：
5.3
通讯作者：
Zou Y
中科院分区：
文献类型：
--
作者：
Yuan L;Qiu L;Ye Y;Wu J;Wang S;Wang X;Zhou N;Zou Y
心肌梗死（MI）后心肌肥厚是心力衰竭的独立危险因素。心肌肥厚的消退已成为治疗MI患者的一种有前途的策略。在这里，我们已经提出，热休克转录因子1（HSF 1）是一种新的抑制剂缺血诱导的心肌肥大。分别在HSF 1缺陷杂合子（KO）、HSF 1转基因（TG）小鼠及其野生型（WT）同窝仔中，使用左冠状动脉前降支结扎来产生MI。采用缺氧处理新生大鼠心肌细胞（NRCMs），模拟MI。在MI后1周的小鼠左心室（LV）梗死边缘区和缺氧处理的NRCM中，HSF 1磷酸化显著降低。与WT MI小鼠相比，HSF 1 KO小鼠在MI后1周表现出更显著的适应不良心脏肥大和心功能不全恶化。通过siRNA转染的HSF 1缺陷显著增加了NRCM中缺氧诱导的心肌肥大。机制上，Janus激酶2（JAK 2）及其效应子、信号转导子和转录激活子3（STAT 3）在MI后WT小鼠的LV梗死边缘区以及缺氧处理的NRCM中被发现显著增加。这些变化在HSF 1 KO小鼠和用HSF 1 SiRNA转染的NRCM中更为显著。因此，HSF 1 TG小鼠在LAD结扎后1周与WT同窝小鼠相比显示出显著改善的心脏肥大和心力衰竭。我们的数据共同表明，HSF 1是通过调节JAK 2/STAT 3信号转导在心肌梗死后的病理性心肌肥大的关键参与，并可能构成一个潜在的治疗心肌梗死患者的目标。
Cardiac hypertrophy after myocardial infarction (MI) is an independent risk factor for heart failure. Regression of cardiac hypertrophy has emerged as a promising strategy in the treatment of MI patients. Here, we have been suggested that heat‐shock transcription factor 1 (HSF1) is a novel repressor of ischaemia‐induced cardiac hypertrophy. Ligation of left anterior descending coronary was used to produce MI in HSF1‐deficient heterozygote (KO), HSF1 transgenic (TG) mice and their wild‐type (WT) littermates, respectively. Neonatal rat cardiomyocytes (NRCMs) were treated by hypoxia to mimic MI in vitro. The HSF1 phosphorylation was significantly reduced in the infarct border zone of mouse left ventricles (LVs) 1 week after MI and in the hypoxia‐treated NRCMs. HSF1 KO mice showed more significant maladaptive cardiac hypertrophy and deteriorated cardiac dysfunction 1 week after MI compared to WT MI mice. Deficiency of HSF1 by siRNA transfection notably increased the hypoxia‐induced myocardial hypertrophy in NRCMs. Mechanistically, Janus kinase 2 (JAK2) and its effector, signal transducer and activator of transcription 3 (STAT3) were found to be significantly increased in the LV infarct border zone of WT mice after MI as well as the NRCMs treated by hypoxia. These alterations were more significant in HSF1 KO mice and NRCMs transfected with HSF1 SiRNA. Inversely, HSF1 TG mice showed significantly ameliorated cardiac hypertrophy and heart failure 1 week after LAD ligation compared to their WT littermates. Our data collectively demonstrated that HSF1 is critically involved in the pathological cardiac hypertrophy after MI via modulating JAK2/STAT3 signalling and may constitute a potential therapeutic target for MI patients.
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热休克转录因子 1 通过 Smad3 防止压力超负荷诱导的心脏纤维化
DOI：
10.1007/s00109-016-1504-2
发表时间：
2017-04
期刊：
Journal of molecular medicine (Berlin, Germany)
影响因子：
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作者：
Zhou N;Ye Y;Wang X;Ma B;Wu J;Li L;Wang L;Wang DW;Zou Y
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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