Abstract 13073: Epicardial YAP/TAZ Regulate an Immune Suppressive Response Following Myocardial Infarction
Ischemic heart disease constitutes the most prevalent type of heart disease in the US. Remodeling post-myocardial infarction (MI) is a multifaceted process driven by a strong immune response. Regulatory T-cells, a subset of CD4+ T-cells, have been shown to suppress the innate and adaptive immune response following myocardial injury to allow for less deleterious remodeling. To date, the precise mechanism by which injured myocardium recruits these suppressive immune cells remains unknown. Here, we show a novel role for the epicardium in suppressing the post-infarct inflammation response through recruitment of T-regulatory cells. The Hippo pathway is a signal transduction pathway, which has gained importance in determining organ size and is implicated as a critical regulator of tissue regeneration. Mice deficient in epicardial YAP/TAZ, two core effectors of the Hippo signaling pathway, develop profound pericardial inflammation, thoracic adhesions and myocardial fibrosis post-MI, with resultant cardiomyopathy and death. These mice demonstrate fewer suppressive T-regulatory cells in the injured myocardium, due to a deficiency of interferon-gamma, a known inducer of these T-cells. Collectively, these results suggest a novel role for Hippo signaling in immune regulation. In addition, our data suggest that the epicardium plays an important role in homing suppressive T-regulatory cells to injured myocardium so that the inflammation response may be attenuated following MI.
Author Disclosures: V. Ramjee: None. M.K. Singh: None. F. Liu: None. K.A. Engleka: None. L.J. Manderfield: None. E.N. Olson: None. J.A. Epstein: None.
- © 2015 by American Heart Association, Inc.