Abstract 370: Interferon Regulatory Factors 3 and 7 Regulate Vein Graft Remodeling and Vascular Inflammation

Introduction: Type I interferons (IFN) are implicated in the development of vascular proliferative diseases. Pathway analysis by gene set enrichment analysis of hypercholesterolemic ApoE3*Leiden murine vein grafts revealed that the type I IFN pathway belonged to the top 15 of significant regulated pathways. The transcriptional regulators of type I IFN and type I IFN responsive genes are the interferon regulatory factors (IRF). Activation of TLR3 results in activation of type I IFN in a IRF3 and IRF7 dependent manner. TLR3 has been shown to be protective in vascular remodeling. The aim of this study was to investigate the role of IRF3 and IRF7 on vein graft remodeling. Methods and Results: The importance of IRFs in vein graft remodeling is illustrated by the increase in vein graft thickening in Irf3-/- and Irf7-/- mice in comparison to control mice (n=9/group, Irf3-/-; 39%, p=0.185, Irf7-/-; 68% p=0.003). Also an increase in outward remodeling (Irf3-/-; 26%, p=0.081, Irf7-/-; 42%, p=0.049) was observed com...