Abstract P3095: Il-1 Signaling On Vascular Smooth Muscle Cells Accelerates Atherosclerosis After Murine Kawasaki Disease Vasculitis

Abstract

Objective: We have previously shown that Lactobacillus casei cell wall extract (LCWE)-induced Kawasaki disease (KD) vasculitis significantly accelerates atherosclerosis in hypercholesterolemic mice. IL-1 signaling is known to play a key role in both KD vasculitis and in the development of atherosclerosis. Here, we investigated the contribution of IL-1 signaling on vascular smooth muscle cells (VSMCs) during KD vasculitis-induced acceleration of atherosclerosis. Methods: Tamoxifen-inducible VSMC-specific IL-1 receptor ( Il1r1) knockout ( Myh11 Cre -ERT2 Il1r1 Δ/Δ )and Il1r1 fl/fl littermate control mice, all on ApoE -/- background, were injected with either PBS or LCWE. Following induction of KD vasculitis, mice were fed a tamoxifen diet for 2 weeks to induce Il1r1 deletion on VSMCs, before being exposed to 8 weeks of Western diet (WD) to promote atherosclerosis. Results: KD vasculitis was associated with a significant acceleration of atherosclerosis, as expected. Specific deletion of Il1r1 on VSMCs reduced this effect, as characterized by significantly decreased plaque size, lipid composition, macrophage infiltration and necrotic core formation in aortic root, as well as diminished lipid accumulation in aorta en face measurements. Conclusions: Our results suggest an important pathophysiologic link between IL-1 signaling, specifically on VSMCs, and subsequent acceleration of atherosclerosis in hypercholesterolemic mice following KD vasculitis. Thus, further studies are warranted on the role of IL-1 signaling not only in acute KD, but also in the subsequent vascular remodeling and complications following acute KD vasculitis.