Signal transducers and transcriptional activation 1 (Stat1) is a member of the STATs family, and its role in various biological responses, including cell proliferation, differentiation, migration, apoptosis, and immune regulation has been extensively studied. We aimed to investigate its role in pathological cardiac hypertrophy, which is currently poorly understood. Experiments using H9C2 cardiomyocytes, Stat1, and IfngR cardiomyocyte‐specific knockout mice revealed that Stat1 had a protective effect on cardiac hypertrophy. Using transverse aortic constriction (TAC)‐induced cardiac hypertrophy in mice, we analyzed the degree of hypertrophy using echocardiography, pathology, and at the molecular level. Mice lacking Stat1 had more pronounced cardiac hypertrophy and fibrosis than wild‐type TAC mice. Analysis of the molecular mechanisms suggested that Stat1 downregulated the mRNA levels of hypertrophy and fibrosis markers to inhibit cardiac hypertrophy, and promotes mitochondrial fission through the Ucp2/P‐Drp1 pathway, enhancing mitochondrial function, and increasing compensatory myocardial ATP production in the compensatory phase for cardiac hypertrophy inhibition. Overall, this comprehensive analysis revealed that Stat1 inhibits cardiac hypertrophy by downregulating hypertrophic and fibrotic marker genes and enhancing the mitochondrial function to enhance cardiomyocyte function through the Ucp2/P‐Drp1 signaling pathway.

中文翻译：

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信号转导和转录激活 1 防止压力超负荷引起的心脏肥大

信号转导和转录激活 1 (Stat1) 是 STATs 家族的成员，其在各种生物反应中的作用，包括细胞增殖、分化、迁移、凋亡和免疫调节已被广泛研究。我们旨在研究其在病理性心脏肥大中的作用，目前对此知之甚少。使用 H9C2 心肌细胞、Stat1 和 IfngR 心肌细胞特异性敲除小鼠的实验表明，Stat1 对心脏肥大具有保护作用。使用横向主动脉缩窄 (TAC) 诱导的小鼠心脏肥大，我们使用超声心动图、病理学和分子水平分析了肥大的程度。与野生型 TAC 小鼠相比，缺乏 Stat1 的小鼠心脏肥大和纤维化更明显。分子机制分析表明，Stat1 下调肥厚和纤维化标志物的 mRNA 水平以抑制心肌肥厚，并通过 Ucp2/P-Drp1 通路促进线粒体裂变，增强线粒体功能，增加代偿期心肌 ATP 的产生。心脏肥大抑制。总体而言，该综合分析表明，Stat1 通过下调肥厚和纤维化标记基因和增强线粒体功能来抑制心肌肥厚，从而通过 Ucp2/P-Drp1 信号通路增强心肌细胞功能。在心脏肥大抑制的代偿期增加代偿性心肌 ATP 的产生。总体而言，该综合分析表明，Stat1 通过下调肥厚和纤维化标记基因和增强线粒体功能来抑制心肌肥厚，从而通过 Ucp2/P-Drp1 信号通路增强心肌细胞功能。在心脏肥大抑制的代偿期增加代偿性心肌 ATP 的产生。总体而言，该综合分析表明，Stat1 通过下调肥厚和纤维化标记基因和增强线粒体功能来抑制心肌肥厚，从而通过 Ucp2/P-Drp1 信号通路增强心肌细胞功能。