Abstract 13539: A Remarkable Anti-fibrotic Role of Spleen-derived Interleukin-10 in High-fat-diet-induced Atrial Inflammatory Fibrosis in Mice
Background: Obesity, characterized by systemic low-grade inflammation, is a risk factor for atrial fibrosis and atrial fibrillation (AF). Spleen reserves monocytes, which deploys to organs at inflammation. However, responsible key molecules linking these two remain undetermined.
Objectives: We tested the hypothesis that a reduction of spleen-derived interleukin-10 (IL-10) would promote atrial fibrosis and AF vulnerability in a high-fat-diet (HFD)-induced mouse obesity model.
Methods: 1) Six-week old male CL57/B6 mice were divided into a HFD group (n=14) and a standard diet group (n=14). 2) Splenectomy was undergone in some CL57/B6 mice (n=14). 3) IL-10 knockout (KO) mice were also investigated (n=14). 4) Recombinant mouse IL-10 was systemically supplemented to another HFD (n=14) and splenectomy-treated mice (n=14) for 8 weeks.
Results: We observed followings. 1) Compared to standard diet, HFD decreased the splenic mRNA level of IL-10 (p<0.05) and serum levels of IL-10 (33.53 ± 3.45 pg/ml vs. 16.41 ± 1.42 pg/ml, p<0.01). Compared to non-splenectomy, splenectomy also decreased serum levels of IL-10 (30.19 ± 1.75 pg/ml vs. 10.87 ± 2.07 pg/ml, p<0.01). 2) HFD and splenectomy enhanced the atrial mRNA levels of tumor necrosis factor-α, monocyte chemoattractant protein-1, F4/80 macrophage antigen, collagen-1 (p<0.05). 3) Atrium isolated from HFD, splenectomy-treated and IL-10 KO mice showed inhomogeneous interstitial fibrosis and abundant infiltration of macrophages, which were reversed by IL-10 supplementation (HFD and splenectomy-treated mice). 4) In isolated-perfused heart experiments, HFD and splenectomy prolonged inter-atrial conduction time (p<0.05). Programmed atrial extrastimuli induced AF in 11 of 14 HFD mice (78.6%) and 6 of 14 splenectomy-treated mice (42.9%), while no AF was induced in 14 standard diet and non-splenectomized mice (78.6% vs. 0%, P<0.001, 42.9% vs. 0%, P<0.05).
Conclusions: These observations demonstrated for the first time that a reduction of spleen-derived IL-10 plays a crucial role in the development of inflammatory atrial fibrosis and enhanced AF vulnerability in HFD-induced obesity mice.
- © 2013 by American Heart Association, Inc.