Multiple studies have shown that the cytokine leukemia inhibitory factor (LIF) is protective of the myocardium in the acute stress of ischemia-reperfusion. All three major intracellular signaling pathways that are activated by LIF in cardiac myocytes have been linked to actions that protect against oxidative stress and cell death, either at the level of the mitochondrion or via nuclear transcription. In addition, LIF has been shown to contribute to post-myocardial infarction cardiac repair and regeneration, by stimulating the homing of bone marrow-derived cardiac progenitors to the injured myocardium, the differentiation of resident cardiac stem cells into endothelial cells, and neovascularization. Whether LIF offers protection to the heart under chronic stress such as hypertension-induced cardiac remodeling and heart failure is not known. However, mice with cardiac myocyte restricted knockout of STAT3, a principal transcription factor activated by LIF, develop heart failure with age, and cardiac STAT3 levels are reported to be decreased in heart failure patients. In addition, endogenously produced LIF has been implicated in the cholinergic transdiffrentiation that may serve to attenuate sympathetic overdrive in heart failure and in the peri-infarct region of the heart after myocardial infarction. Surprisingly, therapeutic strategies to exploit the beneficial actions of LIF on the injured myocardium have received scant attention. Nor is it established whether the purported so-called adverse effects of LIF observed in isolated cardiac myocytes have physiological relevance in vivo. Here we present an overview of the actions of LIF in the heart with the goal of stimulating further research into the translational potential of this pleiotropic cytokine.

中文翻译：

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LIF 和心脏：只是墙上的另一块砖？

多项研究表明，细胞因子白血病抑制因子 (LIF) 在缺血再灌注的急性应激中对心肌具有保护作用。在心肌细胞中由 LIF 激活的所有三个主要细胞内信号通路都与在线粒体水平或通过核转录防止氧化应激和细胞死亡的作用有关。此外，LIF 已被证明有助于心肌梗塞后的心脏修复和再生，通过刺激骨髓来源的心脏祖细胞归巢到受损心肌、驻留心脏干细胞分化为内皮细胞和新血管形成。尚不清楚 LIF 是否在慢性压力下对心脏提供保护，例如高血压引起的心脏重塑和心力衰竭。然而，心肌细胞限制性敲除 STAT3（一种由 LIF 激活的主要转录因子）的小鼠会随着年龄的增长而发生心力衰竭，据报道，心力衰竭患者的心脏 STAT3 水平会降低。此外，内源性 LIF 与胆碱能转分化有关，胆碱能转分化可能有助于减弱心力衰竭和心肌梗塞后心脏梗塞周围区域的交感神经过度驱动。令人惊讶的是，利用 LIF 对受损心肌的有益作用的治疗策略很少受到关注。在离体心肌细胞中观察到的所谓的 LIF 副作用是否在体内具有生理相关性也尚未确定。