Heat‐shock transcription factor 1 is critically involved in the ischaemia‐induced cardiac hypertrophy via JAK 2/ STAT 3 pathway

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 ( HSF 1) is a novel repressor of ischaemia‐induced cardiac hypertrophy. Ligation of left anterior descending coronary was used to produce MI in HSF 1‐deficient heterozygote ( KO ), HSF 1 transgenic ( TG ) mice and their wild‐type ( WT ) littermates, respectively. Neonatal rat cardiomyocytes ( NRCM s) were treated by hypoxia to mimic MI in vitro. The HSF 1 phosphorylation was significantly reduced in the infarct border zone of mouse left ventricles ( LV s) 1 week after MI and in the hypoxia‐treated NRCM s. HSF 1 KO mice showed more significant maladaptive cardiac hypertrophy and deteriorated cardiac dysfunction 1 week after MI compared to WT MI mice. Deficiency of HSF 1 by si RNA transfection notably increased the hypoxia‐induced myocardial hypertrophy in NRCM s. Mechanistically, Janus kinase 2 ( JAK 2) and its effector, signal transducer and activator of transcription 3 ( STAT 3) were found to be significantly increased in the LV infarct border zone of WT mice after MI as well as the NRCM s treated by hypoxia. These alterations were more significant in HSF 1 KO mice and NRCM s transfected with HSF 1 Si RNA . Inversely, HSF 1 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 HSF 1 is critically involved in the pathological cardiac hypertrophy after MI via modulating JAK 2/ STAT 3 signalling and may constitute a potential therapeutic target for MI patients.