Abstract

Atrial fibrillation (AF) is the most common form of cardiac arrhythmia. AF is associated with increased incidence of morbidity and mortality. AF risk factors include hypertension, obesity or right heart disease (RHD). Studies suggest a lower prevalence of AF in adult women compared to men, however, above 50 years old, females with AF have a greater vulnerability to severe complications such as stroke and sudden death. Inflammation has been described among contributors of AF. Our group recently described that inflammation-resolution may prevent AF in RHD, but the mechanism remains unclear. Interleukin-(IL)-37, an inhibitor of the IL1 family was shown to efficiently prevent IL18-induced inflammation. To target the IL1β-IL18 inflammatory axis in vivo and ex vivo the prevent atrial inflammation and AF vulnerability in RHD. IL37 prevents RHD-induced atrial inflammation and AF susceptibility. Pulmonary artery banding (PAB) was performed to induce right-sided cardiac hypertrophy and dilation in male and female Wistar rats (225–275 g). Sham animals did not receive the ligation. Animals were randomized into four groups: Sham and PAB treated or not with IL37 (100 ng/mL/kg). Cardiac echography and physiological studies were performed in vivo before sacrifices at day (D)0, D7, D14 and D21. Right atrial (RA) optical mapping was performed on Langendorff-perfused hearts to analyze the atrial conduction. Histology, western blot, and qPCR were performed to study the expression of proteins and genes involved in atrial inflammation, fibrosis, and electrical remodeling. Twenty-one days after surgery, PAB rats developed severe right-sided hypertrophy and dilation compared to Sham. PAB rats were more vulnerable to AF than Sham. Consistent with clinical evidence, female rats might be more resistant to AF than males. AF was associated with increased RA levels of inflammatory biomarkers including IL1β and IL6. IL37 treatment was associated with decreased atrial expression of inflammatory markers. IL37 is a potential new strategy promoting decreased atrial inflammation and AF prevention in RHD.