AUTHOR=Cabaro Serena , Conte Maddalena , Moschetta Donato , Petraglia Laura , Valerio Vincenza , Romano Serena , Di Tolla Michele Francesco , Campana Pasquale , Comentale Giuseppe , Pilato Emanuele , D’Esposito Vittoria , Di Mauro Annabella , Cantile Monica , Poggio Paolo , Parisi Valentina , Leosco Dario , Formisano Pietro 

TITLE=Epicardial Adipose Tissue-Derived IL-1β Triggers Postoperative Atrial Fibrillation

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.893729

DOI=10.3389/fcell.2022.893729

ISSN=2296-634X

ABSTRACT=<p><bold>Background and aims:</bold> Post-operative atrial fibrillation (POAF), defined as new-onset AF in the immediate period after surgery, is associated with poor adverse cardiovascular events and a higher risk of permanent AF. Mechanisms leading to POAF are not completely understood and epicardial adipose tissue (EAT) inflammation could be a potent trigger. Here, we aim at exploring the link between EAT-secreted interleukin (IL)-1β, atrial remodeling, and POAF in a population of coronary artery disease (CAD) patients.</p><p><bold>Methods:</bold> We collected EAT and atrial biopsies from 40 CAD patients undergoing cardiac surgery. Serum samples and EAT-conditioned media were screened for IL-1β and IL-1ra. Atrial fibrosis was evaluated at histology. The potential role of NLRP3 inflammasome activation in promoting fibrosis was explored <italic>in vitro</italic> by exposing human atrial fibroblasts to IL-1β and IL-18.</p><p><bold>Results:</bold> 40% of patients developed POAF. Patients with and without POAF were homogeneous for clinical and echocardiographic parameters, including left atrial volume and EAT thickness. POAF was not associated with atrial fibrosis at histology. No significant difference was observed in serum IL-1β and IL-1ra levels between POAF and no-POAF patients. EAT-mediated IL-1β secretion and expression were significantly higher in the POAF group compared to the no-POAF group. The <italic>in vitro</italic> study showed that both IL-1β and IL-18 increase fibroblasts’ proliferation and collagen production. Moreover, the stimulated cells perpetuated inflammation and fibrosis by producing IL-1β and transforming growth factor (TGF)-β.</p><p><bold>Conclusion:</bold> EAT could exert a relevant role both in POAF occurrence and in atrial fibrotic remodeling.</p>