Abstract 4372870: IL-37 contributes to the attenuation of inflammation and atrial fibrillation associated with right heart disease.

Introduction: Atrial Fibrillation (AF) is the most common cardiac arrhythmia. Age, obesity as well as heart failure, diabetes or right heart disease (RHD) induced by pulmonary arterial hypertension are important risk factors for AF. Studies have shown that patients with AF associated with RHD symptoms present high levels of circulating pro-inflammatory interleukin-(IL)-18. However, IL-37 an antagonist of the IL-18 receptor, has been shown to prevent inflammation. The role of IL-37 in the context of AF and RHD remains unexplored. Hypothesis: IL-37 reduces atrial inflammation and susceptibility to AF in the context of RHD. Methods: Right-sided cardiac hypertrophy and dilation were induced by pulmonary artery banding (PAB) on male and female Wistar rats (250-300g). PAB was not performed on Sham group. Animals were randomized into four groups and daily injection of IL-37 (1µg/kg) were administered to 50% of the PAB and Sham rats from day 0, 8-hour post-surgery until 3 weeks post-PAB. Echocardiography and electrophysiological studies were performed in vivo before sacrifices. Right atrial optical mapping was performed on Langendorff-perfused freshly excised hearts to analyze the atrial conduction. Protein and gene expression involved in AF were respectively analyzed by Western blot and qPCR. Results: Three weeks after surgery, although IL-37 did not prevent PAB-induced right-sided hypertrophy, PAB rats were more vulnerable to AF than Sham and PAB animals treated with IL-37. Optical mapping revealed reduced right atrial conduction velocity. Treatment with IL-37 induced a decrease in the expression of pro-inflammatory biomarkers (IL-18, IL-6, IL-1β) accompanied with a reduction of right-atrial fibrosis. Conclusion: IL-37 emerges as a potential therapeutic candidate for attenuating atrial inflammation and reducing susceptibility to AF in RHD.