Abstract

Inflammation in post-myocardial infarct (MI) is necessary for myocyte repair and wound healing. Unfortunately it is also a key component of adverse post-myocardial infarction (MI) left ventricular (LV) remodeling that can lead to heart failure. FoxO4 has pleiotropic cell-type and context-dependent functions involved in a variety of human diseases. Recently, we identified a novel function of FoxO4 in post-MI LV remodeling. FoxO4 promotes early post-MI inflammatory response via endothelial Arginase 1 (Arg1). FoxO4 can activate the transcription of endothelial Arg1 in response to ischemia, leading to decreased nitric oxide production and enhanced monocyte adhesion and transmigration through endothelial barrier. Inactivation of FoxO4 resulted in attenuated post-MI inflammation and better preserved cardiac function compared to WT mice. FoxO4 could be a potential therapeutic target in post-MI heart repair and regeneration.