title: LIF and the heart: just another brick in the wall?
abstract: 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.
authors: Department of Pharmacology and Toxicology, School of Medicine, and the Center for Excellence in Cardiovascular-Renal Research, The University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, USA.
authors: Fouad A
authors: FA
authors: Zouein
authors: Mazen
authors: M
authors: Kurdi
authors: George W
authors: GW
authors: Booz
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002316:Cardiotonic Agents / Q000378:metabolism; D006333:Heart Failure / Q000378:metabolism; D006801:Humans; D053605:Leukemia Inhibitory Factor / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D002316:Cardiotonic Agents; D053605:Leukemia Inhibitory Factor; D000109:Acetylcholine
keywords: GP130; JAK STAT signaling; cardiac remodeling; cholinergic transdifferentiation; cytokine; heart failure
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